melphalan and Hodgkin-Disease

High-dose chemotherapy preceding autologous hematopoietic stem cell transplantation (auto-HSCT) is one treatment option for patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL). The most frequently used intensive chemotherapy is a combination of carmustine (BCNU), etoposide, cytarabine and melphalan (BEAM). However, BCNU is consistently in short supply, and there has been a recent dramatic increase in its cost, necessitating the utilization of conditioning alternatives. The busulfan-based conditioning regimen known as the busulfan-cyclophosphamide-etoposide (BuCyE) combination is the second most-studied conditioning regimen worldwide after BEAM, and it exhibits a benefit/risk ratio that is comparable to that of BEAM. In addition to these two combinations, the present manuscript also summarizes data reported for other conditioning combinations. Owing to the lack of prospective and comparative studies, a comparison of the toxicities and medicoeconomical profiles of these treatments is warranted to identify effective replacements for BCNU-based conditioning.

Topics: Antineoplastic Combined Chemotherapy Protocols; Autografts; Carmustine; Cytarabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Melphalan; Podophyllotoxin

High-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) is the standard treatment for relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Until recently, carmustine, etoposide, cytarabine and melphalan (BEAM) was the most commonly used conditioning regimen in this setting, given its acceptable efficacy and tolerability. Despite reasonable success with BEAM, carmustine is associated with a number of acute and late toxicities. Moreover, recent supply and cost issues for this agent have created an urgent need for alternative conditioning regimens. As such, etoposide and melphalan (VP16/MEL) or busulfan, cyclophosphamide, and etoposide (BuCyE) are currently being used with limited success. A number of novel conditioning regimens that replace carmustine with other agents are under investigation, which may provide effective alternatives to BEAM. In considering novel agents to replace carmustine, bendamustine may provide the best alternative, as demonstrated by the results of a number of phase II, multicenter, controlled studies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Drug Resistance, Neoplasm; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Melphalan; Podophyllotoxin; Recurrence; Remission Induction; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Brentuximab Vedotin; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Dexamethasone; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Immunoconjugates; Mechlorethamine; Melphalan; Molecular Targeted Therapy; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prednisone; Procarbazine; Prognosis; Radiotherapy, Adjuvant; Rituximab; Vinblastine; Vincristine

ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) continues to be the standard of care for patients with advanced-stage Hodgkin lymphoma (HL). Consolidation of primary chemotherapy with radiation or autologous stem cell transplantation (ASCT) has not demonstrated an improvement in overall survival in randomized controlled trials. Regimens such as escalated BEACOPP have more acute and late toxicities and survival benefits have yet to be confirmed. Despite effective therapy, ultimately 30% to 40% of patients with advanced HL will relapse. ASCT has become the standard of care for patients with relapsed or refractory HL based on two randomized trials. The optimal salvage chemotherapy and high dose therapy regimen are not known. Similarly, non-ASCT strategies including salvage radiotherapy or non-ASCT chemotherapy strategies have been reported and have a potential role in selected clinical scenarios. This review summarizes recent clinical trial results in the initial treatment of advanced HL and will focus on second-line treatment strategies for patients with relapsed or refractory disease.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Dexamethasone; Disease-Free Survival; Doxorubicin; Etoposide; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Mechlorethamine; Melphalan; Methylprednisolone; Positron-Emission Tomography; Prednisone; Procarbazine; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Salvage Therapy; Transplantation, Autologous; Treatment Outcome; Vinblastine; Vincristine; Vindesine

Significant advances in the biology and treatment of Hodgkin lymphoma (HL) have been accomplished over the past decades. In a landmark study, DeVita and colleagues showed that half of patients with advanced-stage HL experienced long-term disease-free survival following treatment with a four-drug chemotherapy regimen. Subsequent reports and randomized clinical trials conducted over the past 40 years have defined prognostic categories and refined the treatment options for patients with early-stage and advanced-stage HL. New treatment concepts and regimens have continued to increase the cure rate of HL, while other analyses have documented the acute and long-term morbid and potentially fatal side effects of HL therapy. Increased knowledge of HL biology has been gained, in particular, much has been learnt about the genetic and phenotypic characteristics of malignant cells and the varied oncogenic signaling pathways involved in HL. Continued translational research is needed to improve the long-term survival and to lessen the toxicities associated with therapy. Furthermore, continued clinical-trial involvement by oncologists and patients is imperative to further advance the field of HL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials, Phase III as Topic; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Lomustine; Mechlorethamine; Melphalan; Multicenter Studies as Topic; Neoplasm Staging; Prednisone; Procarbazine; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Vinblastine; Vincristine; Vindesine

Intensive therapy and autologous marrow or peripheral blood stem cell transplantation is often utilized in Hodgkin's disease patients whose disease has progressed after primary conventional chemotherapy. A number of studies have described long-term disease-free survival in up to 50% of transplanted patients. High-dose chemotherapy conditioning regimens such as "CBV" or "BEAM" have been used more often than regimens containing total body irradiation. Usually unpurged autologous bone marrow has been utilized as the source of hematopoietic stem cell reconstitution, although recently the use of "primed" peripheral blood stem cells has increased markedly. The challenges of transplant-related toxicity and recurrence of disease post-transplant are discussed, as well as possible strategies to reduce these problems. The use of autologous transplantation is discussed in three clinical settings: patients who have failed to enter a complete remission (CR) after primary chemotherapy, those who have relapsed within 12 months of attaining a CR and those who have relapsed after a longer (i.e., > or = 12 months) first CR. When compared with conventional salvage chemotherapy, transplantation appears to produce a higher long-term disease-free survival rate in all of these patient groups. However, assessment of an advantage for autotransplantation, particularly in patients with long first remissions, is difficult without a Phase III trial. On the other hand, recently updated results from our center indicate that 72% of patients relapsing after long initial remissions benefit from autotransplantation at this point in their disease course, and that transplant-related mortality is low in this setting. Other issues addressed include the potential role of autologous transplantation as consolidation therapy in selected high-risk patients in an initial CR, as well as the utility of conventional chemotherapy and involved-field radiotherapy in conjunction with autotransplantation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Digestive System Diseases; Etoposide; Heart Diseases; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lung Diseases; Melphalan; Multicenter Studies as Topic; Podophyllotoxin; Recurrence; Remission Induction; Salvage Therapy; Survival Rate; Treatment Outcome; Whole-Body Irradiation

Treatment of disseminated Hodgkin's disease still fails in about 50 percent of the cases. The prognosis is poorer in case of early relapse or when the disease is refractory to first-line therapy from the start. Second- or third-line chemotherapy regimens have given rather disappointing results with a complete remission rate usually around 30 percent and a small number of cures. The indications for radiotherapy in localized lymph node relapses remain to be precisely determined. Based on the theoretical dose-effect concept, high-dose chemotherapy followed by autologous bone marrow transplantation increases the number of prolonged complete remissions in patients who respond to salvage chemotherapy. A wider use of haematopoietic growth factors should reduce the toxicity of this treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Carmustine; Cisplatin; Cyclophosphamide; Cytarabine; Dacarbazine; Doxorubicin; Epirubicin; Etoposide; Hodgkin Disease; Humans; Ifosfamide; Mechlorethamine; Melphalan; Methotrexate; Mitoguazone; Prednisone; Procarbazine; Remission Induction; Transplantation, Autologous; Transplantation, Homologous; Vinblastine; Vincristine

The treatment of Hodgkin's disease after relapse from chemotherapy or when resistant to chemotherapy rarely results in cure. For this reason high dose therapy and autologous bone marrow transplantation (ABMT) have been explored in an attempt to overcome drug resistance by drug escalation. The results of studies published to date are encouraging but the procedure is not without significant morbidity and mortality. The answer as to whether high dose therapy and ABMT represent an improvement over conventional salvage therapy will have to await the results of randomized trials. It remains possible that the encouraging results achieved so far have been achieved by inadvertent patient selection.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Carmustine; Cyclophosphamide; Cytarabine; Drug Resistance; Etoposide; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Melphalan; Neutropenia; Pilot Projects; Randomized Controlled Trials as Topic; Registries; Time Factors; Transplantation, Autologous

The incidence of second malignancies was assessed by retrospectively analyzing data from previous studies in well-defined and closely followed patient cohorts. After a median follow-up of more than 6 years following MOPP (mechlorethamine/vincristine/procarbazine/prednisone) chemotherapy with or without radiotherapy, 5% of patients with Hodgkin's disease developed second primaries, 60% of which were leukemias. Melphalan caused a 3% leukemia rate among 1129 patients with ovarian cancer who were followed for a median period of 4 years. No leukemia was observed among 1132 breast cancer patients treated with adjuvant CMF (cyclophosphamide/methotrexate/5-fluorouracil) after a median follow-up of 7.5 years. Long-term, comprehensive studies are needed to improve the current knowledge and the prognosis of patients with second primary neoplasms.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Hodgkin Disease; Humans; Leukemia; Mechlorethamine; Melphalan; Neoplasms, Multiple Primary; Ovarian Neoplasms; Prednisone; Procarbazine; Randomized Controlled Trials as Topic; Retrospective Studies; Vincristine

MOPP chemotherapy was the significant breakthrough that improved the outlook for patients with advanced Hodgkin's disease. Results with alternating potentially non-cross-resistant drug combinations, including MOPP/ABVD, CAD/MOPP/ABV, and MOPP/ABV, are similar and seem to be slightly superior to those with MOPP alone. Limited adjuvant RT does not seem to add appreciably to the morbidity of chemotherapy, although its role in improving on results with chemotherapy alone has not been well studied in prospective, randomized, controlled clinical trials. There are two major challenges for the future. The first is to improve the outcome for advanced Hodgkin's disease patients, perhaps with more intensive chemotherapy and RT with use of cytokines such as the colony-stimulating factors or interleukin-1 or with rescue employing autologous bone marrow transplantation or both. The second challenge is to reduce the morbidity but not the effectiveness of treatment for advanced Hodgkin's disease patients without adverse prognostic factors.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Combined Modality Therapy; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; Leukemia; Lomustine; Lymphoma; Male; Mechlorethamine; Melphalan; Middle Aged; Neoplasms, Multiple Primary; Prednisone; Procarbazine; Remission Induction; Vinblastine; Vincristine; Vindesine

Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Drug Evaluation; Etoposide; Hodgkin Disease; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Lomustine; Melphalan; Mitoxantrone

In a significant fraction of patients with Hodgkin's disease, a condition develops that is resistant to conventional chemotherapy. Experience using high-dose chemotherapy, with or without TBI, and ABMR is expanding. In Hodgkin's disease, remissions can be achieved in approximately half of the patients with relapsed advanced disease. High-dose chemoradiotherapy regimens are toxic and require extensive supportive care. Relapse frequently occurs in areas of previous disease, which suggests failure of the conditioning regimen rather than infusion of occult tumor cells in the autologous bone marrow. Thus, the role of marrow purging in this therapy needs to be evaluated further. It is also important to evaluate the effects of more vigorous attempts at cytoreduction of bulky disease prior to high-dose therapy and ABMR. We recommend that high-dose therapy and ABMR in an investigational setting be used in patients with Hodgkin's disease who experience relapse after MOPP and ABVD or equivalent regimens. Toxicity can be decreased and efficacy increased only if therapy is administered to patients who have not been heavily pretreated and who have lower tumor burden and a good performance status. Finally, high-dose therapy with ABMR has a definite role in salvaging patients with refractory Hodgkin's disease. Many issues need to be resolved, including the optimal timing of this approach and the optimal conditioning regimen. In the years to come these questions may be answered by the many studies now under way.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Dose-Response Relationship, Drug; Hodgkin Disease; Humans; Melphalan; Remission Induction; Transplantation, Autologous; Whole-Body Irradiation

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Doxorubicin; Hodgkin Disease; Humans; Lomustine; Mechlorethamine; Melphalan; Prednisone; Procarbazine; Vinblastine; Vincristine; Vindesine

Topics: Adrenal Cortex Hormones; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Breast Neoplasms; Cyclophosphamide; Dacarbazine; Doxorubicin; Drug Therapy, Combination; Dyspnea; Fluorouracil; Hodgkin Disease; Humans; Hypercalcemia; Leukemia; Leukemia, Lymphoid; Lymphoma; Mechlorethamine; Melphalan; Methotrexate; Multiple Myeloma; Palliative Care; Prednisone; Procarbazine; Receptors, Glucocorticoid; Vinblastine; Vincristine; Vomiting

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Drug Evaluation; Drug Resistance; Etoposide; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Melphalan; Neoplasm Recurrence, Local; Neoplasms; Thioguanine; Transplantation, Autologous

Prognostic factors in patients with Hodgkin's disease and the non-Hodgkin lymphomas are reviewed and discussed since they form the basis of the therapeutic approach to these conditions. Hodgkin's disease is treated according to stage, histology and other prognostic criteria and the appropriate management is presented in tabular form. In the non-Hodgkin lymphomas, prospective studies using the Kiel classification indicated that these lymphomas could be subdivided into types of low-, intermediate- and high-grade malignancy, each requiring different treatment modalities. An expectative approach is often, but not always, recommended in lymphomas of low malignancy. The natural history of lymphomas of high-grade malignancy is unfavourable and, usually, prolonged survival is observed only in those cases in which a complete remission is achieved. Our therapeutic approach to the various forms of these lymphomas is based on the stage of the disease and the respective schedules are summarized for lymphomas of low- and high-grade malignancy. Finally, the chances of cure in Hodgkin's disease and in the non-Hodgkin lymphomas are discussed and recent developments are mentioned.

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Agents; Child; Child, Preschool; Drug Therapy, Combination; Hodgkin Disease; Humans; Lymphoma; Melphalan; Middle Aged; Neoplasm Staging; Procarbazine; Prognosis; Radiotherapy Dosage; Vinblastine

Topics: Adult; Aged; Arsenic; Benzene; Bone Marrow; Breast Neoplasms; Female; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Male; Melphalan; Middle Aged; Multiple Myeloma; Mycosis Fungoides; Ovarian Neoplasms; Paraproteinemias; Waldenstrom Macroglobulinemia

Although cytotoxic immunosuppressive agents play an unquestionably useful role in treating many neoplastic and non-neoplastic disorders, there is accumulating evidence that the toxicity associated with their use is considerable. The therapeutic successes obtained with antitumor agents have led to increases in the life span of cancer patients, but have also provided the opportunity for this toxicity to become manifest. A search of the available literature was carried out, with emphasis on cases in which a malignancy developed in patients following chemotherapy for either neoplastic or non-neoplastic (e.g., renal transplantation, psoriasis) conditions; particular focus was given to the incidence of acute myelogenous leukemia in various groups of Hodgkin's disease and multiple myeloma patients. That patients with nonmalignant conditions treated with cytotoxic immunosuppressive agents are also at increased risk of developing a malignancy raises the possibility that these agents may have oncogenic potential. Therefore, one may be faced with the paradox that the patients benefiting most from chemotherapy may be at highest risk of suffering its consequences.

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Azathioprine; Burkitt Lymphoma; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Female; Hodgkin Disease; Humans; Immunosuppressive Agents; Kidney Neoplasms; Leukemia, Myeloid, Acute; Lymphoma; Mechlorethamine; Melphalan; Mercaptopurine; Methotrexate; Mice; Multiple Myeloma; Neoplasms; Prednisone; Pregnancy; Procarbazine; Time Factors; Vincristine

Topics: 2-Naphthylamine; Alkylating Agents; Antineoplastic Agents; Busulfan; Carcinogens; Cocarcinogenesis; Cyclophosphamide; Female; Hodgkin Disease; Humans; Leukemia; Male; Melphalan; Neoplasms; Nitrogen Mustard Compounds; Radiotherapy; Time Factors

Topics: Adenocarcinoma; Alkylating Agents; Antineoplastic Agents; Breast Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Carmustine; Cyclohexanes; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Hodgkin Disease; Humans; Hydroxyurea; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Melanoma; Melphalan; Multiple Myeloma; Nitrosourea Compounds; Prednisone; Vincristine

Topics: Amyloid; Amyloidosis; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Cyclophosphamide; Hodgkin Disease; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infections; Leukemia, Lymphoid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Prognosis; Pyelonephritis

Topics: Abdominal Neoplasms; Alkylating Agents; Animals; Antimetabolites; Antineoplastic Agents; Carcinoma, Basal Cell; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Dysgerminoma; Female; Fluorouracil; Head; Head and Neck Neoplasms; Hodgkin Disease; Humans; Injections, Intra-Arterial; Leg; Melanoma; Melphalan; Methotrexate; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Nitrogen Mustard Compounds; Pregnancy; Sarcoma; Sarcoma, Ewing; Skin Neoplasms; Vinblastine; Wilms Tumor

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anti-Bacterial Agents; Antineoplastic Agents; Cyclophosphamide; Dactinomycin; Dexamethasone; Folic Acid Antagonists; Hodgkin Disease; Humans; Isoniazid; Mannomustine; Melphalan; Methotrexate; Mitomycin; Mitomycins; Nitrogen Mustard Compounds; Phenylbutazone; Prednisolone; Prednisone; Thiotepa

The aim of this study was to prospectively compare the MIFAP protocol, which had been shown to be effective in patients with relapsed and refractory Hodgkin's lymphoma (HL) or aggressive non-Hodgkin's lymphoma (NHL), to an established regimen like Dexa-BEAM.. Seventy-three adult patients with HL (N = 25) or aggressive NHL (N = 48) suffering from relapse or refractory disease were randomly allocated to receive two cycles of Dexa-BEAM (dexamethasone, carmustine, etoposide, cytarabine, melphalan; N = 37) or MIFAP (mitoxantrone, fludarabine, cytarabine, cisplatin; N = 36) prior to a consolidating high-dose therapy and hematopoietic cell transplantation (HCT). Primary endpoint was the overall response rate (ORR) [complete response (CR) and partial response (PR)] after two courses of salvage chemotherapy.. The ORR was 51% (CR 38%) and 53% (CR 36%) in the Dexa-BEAM arm and in the MIFAP arm (both not significant), respectively. There was a significantly higher grade 3-4 toxicity after MIFAP compared to Dexa-BEAM. Thirty-five patients were consolidated by autologous (N = 29), allogeneic (N = 1) or sequential autologous/allogeneic (N = 5) HCT. No significant differences were found in progression-free survival (PFS) and overall survival (OS) between the Dexa-BEAM and the MIFAP arms.. Compared to Dexa-BEAM, MIFAP is associated with a higher toxicity and does not improve the outcome of patients with recurrent HL or aggressive NHL. For those patients, innovative treatment concepts like recently developed immunotherapies are necessary.. EudraCT number 2021-001937-38.. 7 April 2021, retrospectively registered.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Dexamethasone; Etoposide; Follow-Up Studies; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Melphalan; Neoplasm Recurrence, Local; Prospective Studies; Salvage Therapy

Pretransplant functional imaging (FI), particularly a negative positron emission tomography (PET), is a strong predictor of outcome in adults with relapsed or refractory Hodgkin lymphoma (HL), but data in pediatrics are limited.. The medical records of 49 consecutive pediatric patients, who received autologous transplant at a single institution, were retrospectively analyzed. All patients had either gallium or PET scan before transplant and were conditioned with carmustine, etoposide, cytarabine, and melphalan (BEAM). Deauville scores were retrospectively assigned for patients with PET (score ≥ 4 positive).. Of the 49 patients (median age, 16.2 years), 41 (84%) were pretransplant FI negative and eight (16%) were pretransplant FI positive, after first- to fourth-line salvage therapy, and a median of two salvage cycles. Eighteen patients (37%) received posttransplant radiation. At a median follow up of 46 months, 45 patients (92%) were alive and disease free, and there were three nonrelapse deaths and only one relapse death (Deauville score of 5). The 4-year progression-free survival (PFS) for the entire cohort was 92% (95% confidence interval [CI]: 78-97), and PFS based on pretransplant disease status was 95% (95% CI: 82-99%) in the negative FI group versus 75% (95% CI: 31-93) if positive FI (P = 0.057).. Our analysis revealed outstanding outcomes for children and adolescents with relapsed/refractory HL. There were too few relapses to identify the predictive value of pretransplant metabolic status, but pediatric patients with relapsed/refractory HL and a negative pretransplant FI had excellent survival.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Autografts; Carmustine; Child; Cytarabine; Disease-Free Survival; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Melphalan; Podophyllotoxin; Positron-Emission Tomography; Preoperative Care; Retrospective Studies; Stem Cell Transplantation; Survival Rate

We conducted a prospective phase 2 trial of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) with autologous stem cell transplantation (ASCT) in patients with primary refractory or poor-risk relapsed Hodgkin lymphoma (HL) (ie, extranodal relapse or within 1 year of frontline therapy). The trial was powered to detect an improvement in 2-year progression-free survival (PFS) from a historical 50% using a BEAM regimen (carmustine/etoposide/cytarabine/melphalan) to 65%. We compared the study population with all other concurrent patients who were eligible for the trial but instead received the BEAM regimen at our center. No patient received post-ASCT maintenance therapy. The Gem/Bu/Mel trial enrolled 80 patients with a median age of 31 years, 41% with primary refractory HL and 59% with relapsed HL (36% extranodal relapses), and 30% with positron emission tomography (PET)-positive lesions at ASCT. The concurrent BEAM (n = 45) and Gem/Bu/Mel cohorts were well balanced except for higher rates of bulky relapse and PET-positive tumors in the Gem/Bu/Mel cohort. There were no transplantation-related deaths in either cohort. At a median follow-up of 34.5 months (range, 26 to 72 months), Gem/Bu/Mel was associated with better 2-year PFS (65% versus 51%; P = .008) and overall survival (89% versus 73%; P = .0003). In conclusion, our data show that Gem/Bu/Mel is safe, in this nonrandomized comparison yielding improved outcomes compared with a concurrently treated and prognostically matched cohort of patients with primary refractory or poor-risk relapsed HL receiving BEAM.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carmustine; Cytarabine; Deoxycytidine; Etoposide; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Melphalan; Middle Aged; Salvage Therapy; Survival Analysis; Transplantation, Autologous; Young Adult

The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. We here report a post hoc analysis of this trial after a median follow-up of 10 years.. Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months).. The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing second malignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively).. With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Epirubicin; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Incidence; Italy; Kaplan-Meier Estimate; Lomustine; Male; Melphalan; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Prednisone; Procarbazine; Treatment Outcome; Vinblastine; Vincristine; Vindesine

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.

Topics: Adult; Aged; Busulfan; Carmustine; Cyclophosphamide; Cytarabine; Drug Combinations; Etoposide; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; North America; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous

More active high-dose regimens are needed for refractory/poor-risk relapsed lymphomas. We previously developed a regimen of infusional gemcitabine/busulfan/melphalan, exploiting the synergistic interaction. Its encouraging activity in refractory lymphomas led us to further enhance its use as a platform for epigenetic modulation. We previously observed increased cytotoxicity in refractory lymphoma cell lines when the histone deacetylase inhibitor vorinostat was added to gemcitabine/busulfan/melphalan, which prompted us to clinically study this four-drug combination. Patients ages 12 to 65 with refractory diffuse large B cell lymphoma (DLCL), Hodgkin (HL), or T lymphoma were eligible. Vorinostat was given at 200 mg/day to 1000 mg/day (days -8 to -3). Gemcitabine was infused continuously at 10 mg/m(2)/minute over 4.5 hours (days -8 and -3). Busulfan dosing targeted 4000 μM-minute/day (days -8 to -5). Melphalan was infused at 60 mg/m(2)/day (days -3 and -2). Patients with CD20(+) tumors received rituximab (375 mg/m(2), days +1 and +8). We enrolled 78 patients: 52 DLCL, 20 HL, and 6 T lymphoma; median age 44 years (range, 15 to 65); median 3 prior chemotherapy lines (range, 2 to 7); and 48% of patients had positron emission tomography-positive tumors at high-dose chemotherapy (29% unresponsive). The vorinostat dose was safely escalated up to 1000 mg/day, with no treatment-related deaths. Toxicities included mucositis and dermatitis. Neutrophils and platelets engrafted promptly. At median follow-up of 25 (range, 16 to 41) months, event-free and overall survival were 61.5% and 73%, respectively (DLCL) and 45% and 80%, respectively (HL). In conclusion, vorinostat/gemcitabine/busulfan/melphalan is safe and highly active in refractory/poor-risk relapsed lymphomas, warranting further evaluation. This trial was registered at ClinicalTrials.gov (NCI-2011-02891).

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Deoxycytidine; Drug Administration Schedule; Female; Follow-Up Studies; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Hydroxamic Acids; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell; Male; Melphalan; Middle Aged; Recurrence; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Vorinostat

More active high-dose chemotherapy (HDC) regimens are needed for refractory Hodgkin's lymphoma (HL). We report a cohort analysis of 180 consecutive patients with primary refractory or poor-risk relapsed HL treated with busulfan-melphalan (Bu-Mel) (n = 39), gemcitabine-busulfan-melphalan (Gem-Bu-Mel) (n = 84), or BEAM (BCNU, etoposide, ara-C, melphalan; n = 57) between 2005 and 2010. Their pre-HDC positron emission tomography (PET) scans were interpreted prospectively. Despite more prevalent poor-risk features in the Gem-Bu-Mel cohort, such as PET-positive tumors at HDC, tumors growing at HDC, extranodal disease, or bulky tumors at prior relapse, this cohort had improved outcomes compared with the Bu-Mel and BEAM cohorts, with event-free survival (EFS) rates of 57%, 33%, and 39%, respectively (P = .01), at median follow-up of the whole population of 36 months (range, 3 to 72). Their respective overall survival (OS) rates were, respectively, 82%, 52%, and 59% (P = .04). Secondary acute myelogenous leukemia was seen in 5 patients after BEAM but was not seen in Gem-Bu-Mel and Bu-Mel cohorts (P = .004). Multivariate analyses showed independent adverse effects of an HDC regimen different from Gem-Bu-Mel (hazard ratio [HR] for EFS = 2.3, P = .0008; HR for OS = 2.7, P = .0005), positive PET at HDC (HR for EFS = 2.2, P = .004, HR for OS = 3.1, P = .0001), and >1 previous salvage line (HR for EFS = 1.9, P = .008, HR for OS = 1.8, P = .07). Gem-Bu-Mel improved outcomes in this cohort analysis of patients with refractory/poor-risk relapsed HL and merits evaluation in randomized phase III trials.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Deoxycytidine; Drug Administration Schedule; Female; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Radionuclide Imaging; Recurrence; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Deoxycytidine; Female; Gemcitabine; Hodgkin Disease; Humans; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Recurrence; Remission Induction; Salvage Therapy; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine; Young Adult

A BEAM regimen including carmustine (BiCNU: bis-chloroethyl nitrosourea), etoposide, cytarabine (cytosine arabinoside), and melphalan is a widely used conditioning regimen for autologous stem cell transplant in patients with Hodgkin lymphoma. We report the results of noncryopreserved autologous stem cell transplant of 45 patients with Hodgkin lymphoma given an alternative regimen, modified BEAM-like regimen (CEAM regimen: lomustine, etoposide, cytarabine, and melphalan), in which carmustine (BiCNU IV) was substituted by oral lomustine (CCNU: 2 chloroethyl cyclohexyl nitrosourea).. Forty-five eligible patients with relapsed/refractory Hodgkin lymphoma were consecutively enrolled and underwent conditioning regimen with BEAM-like regimen protocol as follows: Lomustine 200 mg/m(2) on day -3; etoposide 1000 mg/m(2) on day -3 and -2; cytarabine 1000 mg/m(2) on days -3, -2; and Melphalan 140 mg/m(2) on day -1.. All 45 patients showed engraftment of infused stem cell, and there was no graft failure in the study group. The median mononuclear cell dose was 3.4 × 10(8). The median time to absolute neutrophil count > 0.5 × 10(9)/L was 11 days, and the median time to platelet count > 20 × 10(9) was 14 days. Grade 2 and grade 3 mucositis was seen in 64.5% our patients. Transplant-related mortality at 100 days occurred in 1 patient (2.2%). With a median follow-up of 27 months, median disease-free survival was 20 months, mean overall survival was 27 months, and median overall survival has not yet been reached.. These data demonstrate the safety and feasibility of BEAM-like regimen as a new and modified regimen; longer follow-up is required to evaluate fully efficacy and long-term safety of our method.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cryopreservation; Cytarabine; Etoposide; Feasibility Studies; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lomustine; Male; Melphalan; Middle Aged; Prognosis; Recurrence; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

We investigated the administration of intravenous (i.v.) busulfan (Bu) combined with melphalan (Mel) in patients with advanced lymphoid malignancies undergoing autologous stem cell transplantation. Bu 130 mg/m(2) was infused daily for 4 days, either as a fixed dose per body surface area (BSA), or to target an average daily area under the curve of 5000 μmol-min, determined by a test dose of i.v. Bu at 32 mg/m(2) given 48 hours prior to the high-dose regimen, followed by a rest day, followed by 2 daily doses of Mel at 70 mg/m(2). Stem cells were infused the following day. Eighty patients had i.v. Bu delivered per test dose guidance. The median daily systemic Bu exposure was 4867 μmol-min. One hundred two patients (Hodgkin lymphoma n = 49, non-Hodgkin lymphoma n = 12, multiple myeloma = 41) with a median age of 44 years (range: 19-65 years) were treated. The 2-year overall survival and progression-free survival rates were 85% and 57%, respectively, for patients with Hodgkin lymphoma, 67% and 64%, respectively, for patients with non-Hodgkin lymphoma, and 82% and 42%, respectively, for patients with multiple myeloma. The regimen was very well tolerated with treatment-related mortality at 100 days, 1 year, and 2 years of 1%, 3%, and 3%, respectively. Intravenous Bu-Mel was well tolerated. Disease control wa encouraging, and should be explored in larger phase II studies.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Infusions, Intravenous; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Male; Melphalan; Middle Aged; Multiple Myeloma; Severity of Illness Index; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Young Adult

We designed a phase 1-2 study to evaluate the safety and the efficacy of increasing doses of bendamustine (160 mg/m², 180 mg/m², and 200 mg/m² given on days -7 and -6) coupled with fixed doses of etoposide, cytarabine, and melphalan (BeEAM regimen) as the conditioning regimen to autologous stem cell transplantation for resistant/relapsed lymphoma patients. Forty-three patients (median age, 47 years) with non-Hodgkin (n = 28) or Hodgkin (n = 15) lymphoma were consecutively treated. Nine patients entered the phase 1 study; no patients experienced a dose-limiting toxicity. Thirty-four additional patients were then treated in the phase 2. A median number of 6 × 10⁶ CD34(+) cells/kg (range, 2.4-15.5) were reinfused. All patients engrafted, with a median time to absolute neutrophil count > 0.5 × 10⁹/L of 10 days. The 100-day transplantation-related mortality was 0%. After a median follow-up of 18 months, 35 of 43 patients (81%) are in complete remission, whereas 6 of 43 relapsed and 2 of 43 did not respond. Disease type (non-Hodgkin lymphomas vs Hodgkin disease) and disease status at transplantation (chemosensitive vs chemoresistant) significantly influenced DFS (P = .01; P = .007). Remarkably, 4 of 43 (9%) patients achieved the first complete remission after receiving the high-dose therapy with autologous stem cell transplantation. In conclusion, the new BeEAM regimen is safe and effective for heavily pretreated lymphoma patients. The study was registered at European Medicines Agency (EudraCT number 2008-002736-15).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Cytarabine; Drug Resistance, Neoplasm; Etoposide; Female; Follow-Up Studies; Graft Survival; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Nitrogen Mustard Compounds; Recurrence; Remission Induction; Salvage Therapy; Transplantation Conditioning; Transplantation, Autologous

We performed a clinical study of a triple-drug combination to evaluate its efficacy to prevent both acute and delayed emesis after high-dose chemotherapy with BEAM (BCNU [carmustine]+etoposide+ARA-C [cytarabine]+melphalan) before hematopoietic stem cell transplantation (HSCT) by comparison with a historical control group of patients treated with dexamethasone (dex) and ondansetron or palonosetron.. We evaluated 96 patients non-Hodgkin's lymphomas (n=54), and Hodgkin's disease (n=42). Evaluated patients received: aprepitant+palonosetron and dex. The observation period started with the initiation of chemotherapy (0 hours) and continued for 24 hours after the completion of the chemotherapy for the acute phase, and during 5 days after finishing chemotherapy for the delayed phase. The response rate to study drugs was evaluated using a four-grade scale based on the degree of control of nausea and vomiting: high, modrate, slightly effective, or not effective.. Patients treated with the three-drug combination showed a significantly higher response rate than those receiving palonosetron or ondasetron (+dex) during the both the acute and the delayed phases: highly effective early+late phases, 82% versus 70% versus 35%; highly effective early phase, 94% versus 70% versus 35%; highly effective late phase, 85% versus 85% versus 50%; highly+moderately effective early phase, 97% versus 70% versus 40%; highly+moderately effective late phase, 97% versus 90% versus 60%, for triple combination, palonosctron with dexamethasone and ondasetron+dex, respectively. All antiemetic regimens were well tolerated. The three-drug combination showed a similar safety profile; adverse events were generally mild and transient.. The triple-drug combination was more effective than ondansetron or palonosetron (+dex) treatments to prevent acute (especially) and delayed nausea and vomiting following BEAM before HSCT.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carmustine; Cytarabine; Dexamethasone; Drug Therapy, Combination; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Isoquinolines; Lymphoma, Non-Hodgkin; Male; Melphalan; Morpholines; Nausea; Ondansetron; Palonosetron; Quinuclidines; Transplantation, Autologous; Treatment Outcome; Vomiting

Oral mucositis (OM) is an unresolved problem among patients treated with a high-dose therapy supported by hematopoietic stem cell transplantation (HSCT). We tested the ability of supersaturated calcium phosphate mouth rinse (Caphosol) to ameliorate oral mucosal injury induced by a conditioning regimen.. Thirty-two patients with hematologic malignancies were treated with Caphosol to prevent OM during HSCT procedures. The conditioning regimens for 16 patients were BGNU 300 mg/m2, day 6; ARA-C 200 mg/m2 daily, days 5, 4, 3, 2; VP-16 200 mg/m2 daily, days 5, 4, 3, 2; L-PAM 140 mg/m2, day 1 (BEAM) and for 16 patients, MEL 200 (non-Hodgkin's lymphoma). A control group was composed of 24 consecutive patients, who had been treated with HSCT before Caphosol was available. The source of the graft was autologous peripheral blood.. Among patients treated with Caphosol no one had to receive total parenteral nutrition. Among the BEAM group no one experienced III to IV degree OM compared with 40% of the control group. The median OM duration was 2.25 days versus controls of 8.6, (P<.001); only one patient received opioids versus 100% of controls. In the MEL 200 group, 93.7% of patients developed 0 to II degree OM vs 94% of the control group (P=.74) with median duration of 1, 73 days versus 2.42 for the controls (P=.73). In both control and Caphosol cohorts one patient received opioids.. Caphosol may reduce the incidence, severity, and duration of oral mucositis and decrease the number of days with painkillers among patients treated with a BEAM but not a Mel 200 regimen.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Calcium Phosphates; Carmustine; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mouthwashes; Multiple Myeloma; Stomatitis; Transplantation Conditioning; Treatment Outcome; Young Adult

The role of reduced-intensity conditioning allogeneic stem cell transplantation in relapsed/refractory Hodgkin's lymphoma remains poorly defined. We here present an update of our single-center experience with fludarabine-melphalan as a preparative regimen.. Fifty-eight patients with relapsed/refractory Hodgkin's lymphoma underwent RIC and allogeneic stem cell transplantation from a matched related donor (MRD; n=25) or a matched unrelated donor (MUD; n=33). Forty-eight (83%) had undergone prior autologous stem cell transplantation. Disease status at transplant was refractory relapse (n=28) or sensitive relapse (n=30).. Cumulative day 100 and 2-year transplant-related mortality rates were 7% and 15%, respectively (day 100 transplant-related mortality MRD vs. MUD 8% vs. 6%, p=ns; 2-year MRD vs. MUD 13% vs. 16%, p=ns). The cumulative incidence of acute (grade II-IV) graft-versus-host disease in the first 100 days was 28% (MRD vs. MUD 12% vs. 39%, p=0.04). The cumulative incidence of chronic graft-versus-host disease at any time was 73% (MRD vs. MUD 57% vs. 85%, p=0.006). Projected 2-year overall and progression-free survival rates are 64% (49-76%) and 32% (20-45%), with 2-year disease progression/relapse at 55% (43-70%). There was no statistically significant differences in overall survival progression-free survival, and disease progression/relapse between MRD and MUD transplants. There was a trend for the response status pretransplant to have a favorable impact on progression-free survival (p=0.07) and disease progression/relapse (p=0.049), but not on overall survival (p=0.4). Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in progression-free survival Hodgkin's lymphoma is associated with a significant reduction in transplant-related mortality, with comparable results in MRD and MUD allografts. Optimizing pretransplant response status may improve patients' outcome.

Topics: Adult; Disease-Free Survival; Female; Follow-Up Studies; Hodgkin Disease; Hospitals, University; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Pilot Projects; Prospective Studies; Recurrence; Stem Cell Transplantation; Survival Rate; Tissue Donors; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

Limited information is available regarding the use of amifostine in pediatric hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin, etoposide +/- cyclophosphamide is a commonly used preparatory regimen in pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of the addition of amifostine (750 mg/m b.i.d. x 4 d) to melphalan (200 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively) followed by autologous HSCT. Thirty-two patients with a variety of pediatric solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2, and 6 at level 3. Major toxicities during the administration of the preparatory regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required aggressive calcium supplementation during the conditioning phase. No dose limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4 days can be administered with a double alkylator regimen consisting of melphalan (200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) with manageable toxicities.

Topics: Adolescent; Adult; Amifostine; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Bone Neoplasms; Carboplatin; Central Nervous System Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Etoposide; Feasibility Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Hypocalcemia; Kidney Neoplasms; Melphalan; Neoplasms; Neuroblastoma; Pilot Projects; Recurrence; Risk Factors; Sarcoma; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Wilms Tumor

High-dose chemotherapy (HD-CT) with autologous stem cell transplantation is considered to be the treatment of choice for relapsed high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) patients, but the optimal treatment has not yet been defined. We evaluated a salvage treatment regimen consisting of conventional cycles with ifosfamide, etoposide, cytarabine, and dexamethasone (IVAD) followed by two cycles of HD-CT consisting of cyclophosphamide, melphalan, and etoposide (CMV) with autologous stem cell support in patients with relapsed or refractory NHL (n = 59) and HL (n = 16). Response to IVAD was complete remission (CR) in 16 patients (21%), partial remission (PR) in 39 patients (52%), stable disease (SD) in 18 patients (24%), and progressive disease (PD) in two patients (2.7%). Of 70 patients treated with HD-CT, 41 patients (59%) showed a CR, 20 patients a PR (29%), eight patients a SD (11%), and one patient a PD (1.4%). The 5-yr overall survival for the entire group of patients was 29%, and for patients with NHL and HL 25%, and 38%, respectively. The respective event-free survival probabilities at 5 yr were 22%, 16%, and 31%. Seven treatment-related deaths due to septicemia (three), cardiac arrhythmia (one), pneumonia (one), pneumonitis (one), and toxic epidermal necrolysis (one) were observed. In multivariate analysis, an International Prognostic Index of > or = 2 and resistant disease to first-line chemotherapy were poor independent prognostic factors for the subgroup of patients with NHL. In conclusion, these results indicate that IVAD/CMV is feasible as a salvage therapy for lymphoma patients. This treatment is currently evaluated with the addition of rituximab.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Drug Resistance, Neoplasm; Etoposide; Female; Follow-Up Studies; Gastrointestinal Diseases; Hodgkin Disease; Humans; Ifosfamide; Kaplan-Meier Estimate; Lymphoma; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neutropenia; Peripheral Blood Stem Cell Transplantation; Recurrence; Remission Induction; Salvage Therapy; Sepsis; Survival Rate; Transplantation, Autologous; Treatment Outcome

The introduction of reduced-intensity conditioning (RIC) has enabled the role of allogeneic transplantation to be re-evaluated in Hodgkin lymphoma (HL). While T-cell depletion reduces graft-versus-host disease (GvHD), it potentially abrogates graft-versus-tumour activity and increases infective complications. We compared the results in 67 sibling donor transplantations following RIC in multiply relapsed patients from two national phase II studies conditioned with fludarabine/melphalan. One used cyclosporine/alemtuzumab (MF-A, n = 31), the other used cyclosporine/methotrexate (MF, n = 36) as GvHD prophylaxis. There was a small excess of chemorefractory cases in the MF cohort (P = NS). MF-A resulted in significantly lower incidences of non-relapse mortality, acute and chronic GvHD, but no significant excess of relapse/progression. Post donor lymphocyte infusion (DLI) disease responses occurred in 8/14 (57%) and 6/11 (55%) patients in the MF-A and MF groups, respectively. Current progression-free survival (CPFS) was superior with MF-A (univariate analysis), with durable responses to DLI contributing to the favourable outcome (43% vs. 25%, P = 0.0356). Disease status at transplantation significantly influenced overall survival (P = 0.0038) and CPFS (P = 0.0014), retaining significance in multivariate analyses, which demonstrated a trend towards improved CPFS with T-cell depletion (P = 0.0939). These data suggest that alemtuzumab significantly reduced GvHD without resulting in a deleterious impact on survival outcomes following RIC in HL, and that durable responses to DLI may be more common following the inclusion of alemtuzumab in the conditioning protocol.

Topics: Adult; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Agents; Cyclosporine; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphocyte Depletion; Lymphocyte Transfusion; Male; Melphalan; Methotrexate; Middle Aged; Multivariate Analysis; Myeloablative Agonists; Proportional Hazards Models; Retrospective Studies; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine

Topics: Adolescent; Adult; Amifostine; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Cytarabine; Female; Graft Survival; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Podophyllotoxin; Radiation-Protective Agents; Stem Cell Transplantation; Transplantation, Homologous

The multicentre phase III CORAL study aims to guide choice of salvage chemotherapy in diffuse large B-cell lymphoma (DLBCL) and assess the role of rituximab maintenance after autologous stem cell transplantation (ASCT). Patients are first randomised between ICE (ifosfamide, carboplatin, etoposide) and DHAP (dexamethasone, ara-C and cisplatin), both combined with rituximab (R-ICE or R-DHAP). After three courses, responders are treated by ASCT with BEAM. A second randomisation then allocates patients to maintenance treatment with rituximab 375 mg/m(2), one injection every 2 months six times, or observation. Accrual to the study is now proceeding well and the planned 400 patients are likely to be enrolled within the next 1.5 years. Results to date are very preliminary but suggest encouraging rates of response. However, they also indicate that initial exposure to rituximab may increase the difficulty of salvaging patients who fail first-line therapy.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carmustine; Cisplatin; Combined Modality Therapy; Cytarabine; Dexamethasone; Disease-Free Survival; Dose-Response Relationship, Drug; Etoposide; Hodgkin Disease; Humans; Ifosfamide; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Podophyllotoxin; Remission Induction; Rituximab; Salvage Therapy; Stem Cell Transplantation; Survival Rate; Transplantation, Autologous; Treatment Outcome

We designed a dose- and time-intensified high-dose sequential chemotherapy regimen for patients with relapsed and refractory Hodgkin lymphoma (HD).. Eligibility criteria included age 18-65 years, histologically proven primary progressive (PD) or relapsed HD. Treatment consisted of two cycles DHAP (dexamethasone, high-dose cytarabine, cisplatinum); patients with chemosensitive disease received cyclophosphamide followed by peripheral blood stem cell harvest; methotrexate plus vincristine, etoposide and BEAM plus peripheral blood stem cell transplantation (PBSCT).. A total of 102 patients (median age 34 years, range 18-64) were enrolled. The response rate was 80% (72% complete response, 8% partial response). With a median follow-up of 30 months (range 3-61 months), freedom from second failure (FF2F) and overall survival (OS) were 59% and 78% for all patients, respectively. FF2F and OS for patients with early relapse were 62% and 81%, for late relapse 65% and 81%; for PD 41% and 48%, and for multiple relapse 39% and 48%, respectively. In multivariate analysis response after DHAP (P <0.0001) and duration of first remission (PD and multiple relapse versus early and late relapse; P=0.0127) were prognostic factors for FF2F. Response after DHAP (P <0.0081), duration of first remission (P=0.0017) and anemia (P=0.019) were significant for OS.. Based on the promising results of this study, a prospective randomized European intergroup study was started comparing this intensified regimen with two courses of DHAP followed by BEAM (HD-R2 protocol).

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Disease-Free Survival; Dose-Response Relationship, Drug; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Infusions, Intravenous; Injections, Subcutaneous; Male; Melphalan; Methotrexate; Middle Aged; Peripheral Blood Stem Cell Transplantation; Recurrence; Treatment Outcome; Vincristine

Combination chemotherapy can cure patients with non-Hodgkin's lymphoma (NHL), but those who suffer treatment failure or relapse still have a poor prognosis. High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) can improve the outcome of these patients. We evaluated an intensified high-dose sequential chemotherapy program with a final myeloablative course.. Inclusion criteria were age 18-65 years, histologically proven primary progressive or relapsed aggressive NHL and eligibility for HDCT. The therapy consists of two cycles DHAP: dexamethasone 40 mg (day 1-4), high-dose cytarabine 2 g/m2 12q (day 2), cisplatin 100 mg/m2 (day 51); patients with partial (PR) or complete remission (CR) received cyclophosphamide 4 g/m2 (day 37), followed by peripheral blood stem cell (PBSC) harvest; methotrexate 8 g/m2 (day 1) plus vincristine 1.4 mg/m2 (day 51); and etoposide 500 mg/m2 (day 58-62). The final myeloblative course was BEAM: cytarabine 200 mg/m2 12q (day 81-84), etoposide 150 mg/m2 12q (day 81-84), melphalan 140 mg/m2 (day 80), carmustin 300 mg/m2 (day 80) followed by PBSCT.. Fifty-seven patients (median age 43 years, range 24-65) were enrolled: 23 (40%) patients were refractory to primary therapy and 34 (60%) patients had relapsed NHL. The response rate (RR) after 2 cycles of DHAP was 72% (9% CR, 63% PR) and at the final evaluation (100 days post transplantation) 43% (32% CR, 11% PR). Toxicity was tolerable. Median follow-up was 25 months (range 1-76 months). Freedom from second failure (FF2F) and overall survival (OS) at 2 years were 25% and 47% for all patients, respectively. FF2F at 2 years for patients with relapse and for patients refractory to primary therapy were 35% and 9% (P=0.0006), respectively. OS at 2 years for patients with relapse and for patients refractory to primary therapy were 58% and 24% (P=0.0044), respectively.. We conclude that this regimen is feasible, tolerable and effective in patients with relapsed NHL. In contrast, the results in patients with progressive disease are unsatisfactory. This program is currently being modified by addition of rituximab for patients with relapsed aggressive NHL.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Combined Modality Therapy; Cytarabine; Dexamethasone; Disease-Free Survival; Dose-Response Relationship, Drug; Etoposide; Feasibility Studies; Female; Hodgkin Disease; Humans; Infusions, Intravenous; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Salvage Therapy; Stem Cell Transplantation; Survival Rate; Transplantation, Autologous; Treatment Outcome

In this multicenter, prospective, randomized clinical trial on advanced Hodgkin's lymphoma (HL), the efficacy and toxicity of two chemotherapy regimens, doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) and mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine (MOPPEBVCAD), were compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as standard therapy to select which regimen would best support a reduced radiotherapy program, which was limited to < or = two sites of either previous bulky or partially remitting disease (a modification of the original Stanford program).. Three hundred fifty-five patients with stage IIB, III, or IV HL were randomly assigned. Three hundred thirty-four patients were assessable for the study and received six cycles of ABVD (n = 122), three cycles of Stanford V (n = 107), or six cycles of MOPPEBVCAD (n = 106); radiotherapy was administered to 76, 71, and 50 patients in these three arms, respectively.. The complete response rates for ABVD, Stanford V, and MOPPEBVCAD were 89%, 76% and 94%, respectively; 5-year failure-free survival (FFS) and progression-free survival rates were 78%, 54%, 81% and 85%, 73%, and 94%, respectively (P < .01 for comparison of Stanford V with the other two regimens). Corresponding 5-year overall survival rates were 90%, 82%, and 89% for ABVD, Stanford V, and MOPPEBVCAD, respectively. Stanford V was more myelotoxic than ABVD but less myelotoxic than MOPPEBVCAD, which had larger reductions in the prescribed drug doses.. When associated with conditioned and limited (not adjuvant) radiotherapy, ABVD and MOPPEBVCAD were superior to Stanford V chemotherapy in terms of response rate and FFS and progression-free survival. Patients were irradiated less often after MOPPEBVCAD, but this regimen was more toxic. ABVD is still the best choice when it is combined with optional, limited irradiation.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Lomustine; Male; Mechlorethamine; Melphalan; Middle Aged; Prednisone; Procarbazine; Treatment Outcome; Vinblastine; Vincristine; Vindesine

High-dose chemotherapy using melphalan (HDMEL) is an important component of many conditioning regimens that are given before autologous hematopoietic stem cell transplantation (AHSCT). In contrast to the situation in myeloma, and to a lesser degree acute leukemia, only a very limited published experience exists with the use of HDMEL conditioning as a single agent in doses requiring AHSCT for lymphoma, both Hodgkin lymphoma (HL) and especially non-Hodgkin lymphoma (NHL). Thus, we report results of treating 26 lymphoma patients (22 with NHL and four with HL) with HDMEL 220-300 mg/m(2) plus amifostine (AF) cytoprotection and AHSCT as part of a phase I-II trial. Median age was 51 years (range 24-62 years); NHL histology was varied, but was aggressive (including transformed from indolent) in 19 patients, indolent in two patients and mantle cell in one. All 26 patients had been extensively treated; 11 were refractory to the immediate prior therapy on protocol entry and two had undergone prior AHSCT. All were deemed ineligible for other, 'first-line' AHSCT regimens. Of these 26 patients, 22 survived to initial tumor evaluation on D +100. At this time, 13 were in complete remission, including four patients who were in second CR before HDMEL+AF+AHSCT. Responses occurred at all HDMEL doses. Currently, seven patients are alive, including five without progression, with a median follow-up in these latter patients of D +1163 (range D +824 to D +1630); one of these patients had a nonmyeloablative allograft as consolidation on D +106. Conversely, 14 patients relapsed or progressed, including five who had previously achieved CR with the AHSCT procedure. Two patients, both with HL, remain alive after progression; one is in CR following salvage radiotherapy. Six patients died due to nonrelapse causes, including two NHL patients who died while in CR. We conclude that HDMEL+AF+AHSCT has significant single-agent activity in relapsed or refractory NHL and HL. This experience may be used as a starting point for subsequent dose escalation of HDMEL (probably with AF) in established combination regimens.

Topics: Adult; Amifostine; Antineoplastic Agents, Alkylating; Combined Modality Therapy; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Radiation-Protective Agents; Transplantation Conditioning; Transplantation, Autologous

We have undertaken a retrospective sequential-cohort analysis of 131 lymphoma patients treated with the BEAM regimen and autologous stem cell transplantation, to compare BEAM at standard doses (sBEAM; n = 67 from May 1990 to April 1995) and BEAM with escalated etoposide dose from 800 to 1600 mg/m(2) (eBEAM; n = 64 from May 1995 to June 1999). Transplant-related mortality and incidence of secondary malignancies were similar in both groups. Disease progression was significantly lower in indolent lymphoma (IL) patients receiving eBEAM (7 vs 43%), although survival was comparable due to a higher toxic mortality in the eBEAM group. The 5-year event-free survival and overall survival were better in Hodgkin's disease (HD) patients treated with eBEAM (70 and 77%, respectively) compared to sBEAM (58 and 69%, respectively), but the difference was not statistically significant. In aggressive lymphomas, no difference was detected between groups. Our results indicate that while escalation of the etoposide doses in the BEAM conditioning regimen does not appear to improve outcome, encouraging results in IL and HD may warrant further studies.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cohort Studies; Cytarabine; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma; Male; Melphalan; Middle Aged; Multivariate Analysis; Retrospective Studies; Time Factors; Transplantation Conditioning; Transplantation, Autologous

The pharmacokinetics of two etoposide (E) formulations were evaluated in patients with refractory hematologic malignancies receiving high-dose conditioning with autologous stem cell transplantation. Patients were randomized to either E at 800 mg/m(2) (containing polysorbate 80 and polyethylene glycol) or etoposide phosphate (EP) at 910 mg/m(2) on days -7 and -5, prior to melphalan, 80 mg/m(2) on day -5. On day -3, EP was repeated. Plasma E was analyzed after each formulation on days -7 and -5 to compare intrapatient pharmacokinetics. In total, 10 patients were treated: four each with multiple myeloma or Hodgkin's disease and two with non-Hodgkin's lymphoma. Mucositis was the major toxicity with seven patients. EP first produced grade 3 mucositis. There was no procedure-related mortality and eight patients remained alive 1 year post-transplant. Cumulative etoposide exposure (AUC) was slightly greater with EP (P=0.056). Conversely, the volume of distribution was slightly, 33%, larger (P=0.052) and clearance was increased with the E infusion (P=0.14). As none of the differences reached statistical significance, both E formulations appear to be pharmacokinetically equivalent in the high-dose transplant setting. The combination of high-dose EP with melphalan is an active preparative regimen prior to ABMT for hematologic malignancies.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Chromatography, High Pressure Liquid; Etoposide; Hodgkin Disease; Humans; Life Expectancy; Lymphoma; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; Multiple Myeloma; Organophosphorus Compounds; Stem Cell Transplantation; Time Factors; Transplantation, Autologous

We evaluated prognostic factors and treatment outcome of patients with relapsed/refractory Hodgkin's disease (HD) receiving autologous stem cell transplantation (ASCT). In total, 92 patients received total body irradiation, cyclophosphamide and etoposide (TBI/CY/E) (n=42) or busulfan, melphalan and thiotepa (Bu/Mel/T) (n=50) supported with ASCT. A total of 33 (66%) patients receiving the Bu/Mel/T regimen had a prior history of dose-limiting irradiation. Mucositis, hepatic and pulmonary toxicities were the main causes of morbidity and mortality, irrespective of the conditioning regimen. The transplant-related mortality was 15%. With a median follow-up of 6 years (range 2.5-11), the cumulative probabilities of survival, event-free survival (EFS) and relapse at 6 years were 55, 51 and 32%. The 6-year Kaplan-Meier (KM) probabilities of EFS for patients with less advanced disease (patients in first chemotherapy-responsive relapse or second remission (n=42)) and more advanced disease (all other patients (n=50)) were 60 and 44%. No differences in toxicities and efficacy between the conditioning regimens were found. ASCT is an effective treatment for patients with refractory/relapsed HD. Female patients and patients with less advanced disease at transplant had a better outcome. Patients with prior irradiation benefited from the Bu/Mel/T regimen.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Salvage Therapy; Survival Analysis; Thiotepa; Transplantation, Autologous; Treatment Outcome; Whole-Body Irradiation

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Etoposide; Hodgkin Disease; Humans; Melphalan; Prognosis; Recurrence; Stem Cell Transplantation; Transplantation, Autologous

To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin's disease (HD) who failed to respond completely or relapsed after initial treatment.. Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT.. With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P =.0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P =.0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival.. Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Ifosfamide; Male; Melphalan; Middle Aged; Mitoguazone; Recurrence; Salvage Therapy; Transplantation, Autologous; Vinblastine; Vinorelbine

High-dose chemotherapy followed by transplantation of autologous haemopoietic stem cells (BEAM-HSCT) is frequently used to treat patients with relapsed Hodgkin's disease. We aimed to compare this treatment with conventional aggressive chemotherapy without stem-cell transplantation (Dexa-BEAM).. 161 patients between 16 and 60 years of age with relapsed Hodgkin's disease were randomly assigned two cycles of Dexa-BEAM (dexamethasone and carmustine, etoposide, cytarabine, and melphalan) and either two further courses of Dexa-BEAM or high-dose BEAM and transplantation of haemopoietic stem cells. Only patients with chemosensitive disease (complete or partial remission after two courses of Dexa-BEAM) proceeded to further treatment. The primary endpoint was freedom from treatment failure for patients with chemosensitive disease. Analysis was per protocol.. 17 patients were excluded from the study after randomisation (ten given Dexa-BEAM and seven given BEAM-HSCT). Median follow-up was 39 months (IQR 3-78). Freedom from treatment failure at 3 years was significantly better for patients given BEAM-HSCT (55%) than for those on Dexa-BEAM (34%; difference -21%, 95% CI -39.87 to -2.13; p=0.019). Overall survival of patients given either treatment did not differ significantly.. High-dose BEAM and transplantation of haemopoietic stem cells improves freedom from treatment failure in patients with chemosensitive first relapse of Hodgkin's disease irrespective of length of initial remission.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cause of Death; Cytarabine; Dexamethasone; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Recurrence; Salvage Therapy

The magnitude of chemotherapy dose escalation made possible by the use of recombinant haematopoietic growth factors has not been quantified in a randomized trial.. Patients with refractory or relapsing Hodgkin's disease were randomized to receive the Dexa-BEAM regimen with escalating etoposide doses supported by placebo or granulocyte-macrophage colony-stimulating factor (GM-CSF). Using an adaptive sampling method independently in both arms, the etoposide dose was escalated until the maximal tolerated dose for the first cycle was reached.. Thirty patients were randomized to GM-CSF and thirty to placebo. The etoposide dose could be escalated considerably in both treatment arms. Maximal etoposide dose for the first cycle was 1920 mg/m2 for patients receiving GM-CSF and 1160 mg/m2 for patients receiving placebo (P = 0.045 one-sided), corresponding to a 65% higher etoposide dose and a 13% higher dose intensity with GM-CSF. Dose-limiting events were similar in both arms, consisting mainly of prolonged neutropenia and consecutive infections. Treatment efficacy was not different in the two treatment groups.. While GM-CSF permits a somewhat higher dose escalation than placebo, the increase in dose intensity provided by GM-CSF is small. The use of CSF for interval reduction rather than dose escalation is the more effective strategy for dose intensification.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Dexamethasone; Dose-Response Relationship, Drug; Double-Blind Method; Etoposide; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hodgkin Disease; Humans; Leukocyte Count; Male; Maximum Tolerated Dose; Melphalan; Middle Aged; Neoplasm Staging; Treatment Outcome

To evaluate the feasibility, toxicity and preliminary results of a potentially less toxic variant of the MOPPEBVCAD chemotherapy regimen for advanced Hodgkin's disease: MOPPEBVCyED, in which cyclophosphamide and etoposide replace lomustine and melphalan, respectively, with the remaining components being unaltered.. The study was multicenter, prospective and randomized, and enrolled 67 patients with newly diagnosed stage IIB, III, IV Hodgkin's disease (62 were expected on the grounds of statistical considerations). Radiotherapy was restricted to sites of bulky involvement or to areas that responded incompletely to chemotherapy. Median follow-up was 48 months.. Comparing MOPPEBVCAD vs. MOPPEBVCyED, the results were as follows: complete remissions 35/35 vs. 30/32 (plus one partial remission and one disease progression); relapses 5 vs. 8; deaths 2 (one of myelodysplasia) vs. 2; delivered mean dose intensity (DI): lomustine 0.79+/-0.67 vs. cyclophosphamide 0.82+/-0.32; melphalan 0.80+/-0.13 vs. etoposide 0.86+/-0.18; average DI of the 7 drugs common to both regimens 0.73+/-0.10 vs. 0.83+/-0.11; all 9 drugs 0.75+/-0.13 vs. 0.84+/-0.09 (p=0.002); projected 5-year failure-free survival 0.79 vs 0.62; second cancers, two myelodysplasias vs. one carcinoma of the kidney. Toxicities were not statistically different except for heavier thrombocytopenia being recorded with MOPPEBVCAD.. The higher cumulative and single drug DI recorded with MOPPEBVCyED may reflect better short-term tolerability, but it does not lead to better disease control. Its late toxicity may be expected to be lower in the future but at present it does not seem to be a sufficient reason to substitute MOPPEBVCyED for MOPPEBVCAD.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Epirubicin; Etoposide; Female; Hodgkin Disease; Humans; Lomustine; Male; Mechlorethamine; Melphalan; Middle Aged; Prednisone; Procarbazine; Prospective Studies; Treatment Outcome; Vinblastine; Vincristine; Vindesine

Six patients with advanced Hodgkin's disease in which multiple conventional treatments (median prior chemotherapy regimens: seven), radiation therapy, and a prior autologous stem cell transplantation (SCT) had failed underwent allogeneic SCT following a fludarabine-based conditioning regimen. Median age was 29 years (22-30). Median time to progression after autologous SCT was 6 months (4-21). Disease status at transplant was refractory relapse (n = 3) and sensitive relapse (n = 3). Cell source was filgrastim-mobilized peripheral blood stem cells from an HLA-identical sibling (n = 4) or matched unrelated donor marrow (n = 2). Conditioning regimens were fludarabine-cyclophosphamide-antithymocyte globulin (n = 4), fludarabine-melphalan (n = 1) and fludarabine-cytarabine-idarubicin (n = 1). Myeloid recovery was prompt, with an absolute neutrophil count > or =500/microl on day 12 (11-15). Median platelet recovery to > or =20000/microl was on day 9 (0-60). Chimerism studies on day 30 indicated 100% donor-derived hematopoiesis in 4/5 evaluable patients (4/4 non-progressors). All responders (3/3) have ongoing 100% donor-derived chimerism. Acute graft-versus-host disease (GVHD) was diagnosed in 4/6 evaluable patients. Chronic GVHD was present in 2/4 evaluable patients. There were no regimen-related deaths. Overall day 100 transplant-related mortality was 2/6 (33%). Three patients have expired and three are alive and progression-free with a median follow-up of 9 months (6-26) post transplant. We conclude that allogeneic stem cell transplantation with fludarabine-based preparative regimens is feasible in these high-risk, heavily pretreated HD patients.

Topics: Adult; Antilymphocyte Serum; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Female; Follow-Up Studies; Graft vs Host Disease; Graft vs Tumor Effect; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Idarubicin; Immunosuppressive Agents; Immunotherapy, Adoptive; Male; Melphalan; Pilot Projects; Transplantation Conditioning; Vidarabine

To investigate the use of a nonmyeloablative fludarabine-based immunosuppressive regimen to allow engraftment of HLA-sibling donors' mobilized stem cells and induction of a graft-versus-lymphoma effect for patients with advanced resistant Hodgkin's disease and non-Hodgkin's lymphoma.. Fifteen patients with Hodgkin's disease (n = 10) and non-Hodgkin's lymphoma (n = 5) were studied. All patients received cyclophosphamide and granulocyte colony-stimulating factor to mobilize autologous hematopoietic stem cells (HSCs). Subsequently, they received high-dose therapy with carmustine, etoposide, cytarabine, and melphalan and reinfusion of HSCs. At a median of 61 days after engraftment, patients were given fludarabine 30 mg/m(2) with cyclophosphamide 300 mg/m(2) daily for 3 days. Donor-mobilized HSC collections were prepared for fresh infusion and were not T-cell depleted. Methotrexate and cyclosporine were used to prevent graft rejection and as graft-versus-host disease (GVHD) prophylaxis.. Combined treatment was well tolerated. After mini-allografting, hematologic recovery was prompt. Thirteen patients had 100% donor cell engraftment. Eleven patients achieved complete remission (CR) after the combined procedure. Nine patients, who were in partial remission after autografting, achieved CR after mini-allografting. Seven patients developed >/= grade 2 acute GVHD (aGVHD) and two developed extensive chronic GVHD (cGVHD). Three patients who received the highest number of donor lymphocyte infusions (DLIs) developed grade 3 GVHD (two patients) and extensive cGVHD (one patient). Ten patients are currently alive, and five are in continuous CR. Seven patients received DLI, with five CRs. Five patients died: one of progressive disease, two of progressive disease combined with aGVHD or cGVHD, one of extensive cGVHD, and one of infection.. Fludarabine/cyclophosphamide was well tolerated and allowed consistent engraftment in lymphoma allografted patients. Response rates were high in this group of refractory and heavily pretreated patients. This dual procedure seems to be most promising in patients with end-stage malignant lymphomas.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cyclosporine; Cytarabine; Etoposide; Female; Graft vs Tumor Effect; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunosuppressive Agents; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Pilot Projects; Risk Factors; Survival Rate; Transplantation Chimera; Vidarabine

Topics: Adolescent; Adult; Antineoplastic Agents; Carboplatin; Combined Modality Therapy; Etoposide; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; Pilot Projects; Recurrence; Transplantation Conditioning

High-dose chemotherapy and autologous bone marrow transplantation (ABMT) has become the standard approach for most patients with relapsed or refractory Hodgkin's disease. Disease status at transplant has been correlated with outcome following ABMT. In light of this, we employ mini-BEAM (BCNU, etoposide, cytarabine and melphalan) salvage therapy in order to achieve a state of minimal residual disease prior to transplantation.. From February 1992 to June 1998 twenty-four patients receiving mini-BEAM therapy for resistance or relapse of their Hodgkin's disease were included. Four patients had obtained no response with initial chemotherapy (refractory), eight had obtained an incomplete response, seven were in first relapse and five in second or subsequent relapse. Fifteen patients received mini-BEAM as first salvage chemotherapy regimen. The remaining nine patients had previously been exposed to a median of one salvage regimen. Patients received a median of three cycles of mini-BEAM.. Sixteen patients achieved complete remission and four partial remission, yielding an overall response rate of 83%. No significant differences in response were observed between patients who received mini-BEAM as initial salvage therapy and those who had received a prior salvage regimen. Eighteen out of the twenty responding patients went on to intensive therapy and peripheral blood stem cell transplantation. With a median follow-up of 52 months, the cumulative probability of 7-year overall survival is 71% for the responders and that of the 6-year disease-free survival is 42%. No treatment-related deaths were observed.. Mini-BEAM is an effective salvage regimen with moderate toxicity that may be useful for cytoreduction prior to stem cell procedures.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Carmustine; Cytarabine; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Podophyllotoxin; Recurrence; Salvage Therapy; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Disease status before high-dose chemotherapy with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) is an important predictor of transplantation-related toxicity and event-free survival (EFS) for patients with relapsed or refractory Hodgkin's disease (HD). We performed a phase II study in patients with relapsed or refractory HD to evaluate the feasibility of four cycles of Dexa-BEAM followed by high-dose chemotherapy with ABMT or PBSCT.. Twenty-six patients (median age 30, range 20-40 years) were treated with 2-4 courses of dexamethasone, carmustine, etoposide, cytarabine and melphalan (Dexa-BEAM) as salvage chemotherapy in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received high-dose chemotherapy with ABMT or PBSCT. The conditioning regimen used was CVB (cyclophosphamide, carmustine, etoposide).. Eighteen patients responded to Dexa-BEAM, resulting in a response rate of 69%. At the time of transplant 16 patients were in CR two patients in PR. At present 14 patients transplanted are in continuous CR (median follow-up 40 months, range 14-60 months). Two patients with PR after four courses of Dexa-BEAM relapsed and died three months posttransplantation. Two patients with CR at the time of transplant relapsed after nine and 13 months respectively. Eight patients had rapid progressive disease after 2-4 cycles of Dexa-BEAM. One patient with progressive disease died in gram-negative sepsis after four cycles of Dexa-BEAM. There was no transplantation-related death.. These data suggests the use of high-dose chemotherapy followed by stem cell transplantation at the time of maximal response.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Disease-Free Survival; Dose-Response Relationship, Drug; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Salvage Therapy; Survival Rate; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Melphalan

To evaluate the effect of two filgrastim dosages after autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL).. Eighty-six patients were enrolled onto a multicenter, randomized, open-label study. The study compared the efficacy and safety of two different doses of filgrastim, 5-microgram/kg/d subcutaneous (SC) bolus injection and 10-microgram/kg/d SC continuous infusion, starting on day 1 following ABMT.. Both patient groups were well matched in terms of demography and disease. The results showed no statistical difference in the median time to reach an absolute neutrophil count (ANC) of 0.5 x 10(9)/L (11 days; P = .685) and no difference in the median duration of neutropenia (10 v 11 days, respectively; P = .567) between either dose of filgrastim. The incidence and duration of fever and neutropenic fever were the same in both groups. The number and mean duration of clinically and documented infections, duration of intravenous (IV) antibiotics, time to discharge from hospital, and tumor response also were similar in both groups.. This study demonstrates that a dose of filgrastim 5 micrograms/kg/d administered as a daily SC bolus injection has a similar efficacy and safety profile compared with the 10-microgram/kg/d dose administered as a SC continuous infusion. The lower dose of filgrastim has potential cost-saving implications in terms of both the dose of drug administered and the ease of administration. Based on these findings, the recommended dose of filgrastim after ABMT should be 5 micrograms/kg/d.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Mesna; Middle Aged; Neutropenia; Patient Selection; Recombinant Proteins; Thiotepa

A cohort of 76 patients with previous chemotherapy for Hodgkin's disease and non-Hodgkin lymphomas received high-dose carmustine, etoposide, cytosine-arabinoside and melphalan (BEAM) followed by autologous stem cell transplantation (ASCT) and was followed for relapse and development of leukemic complications. Six patients, four with Hodgkin's disease and two with non-Hodgkin lymphomas, developed leukemic complications, myelodysplasia (MDS) in four cases and overt acute myeloid leukemia (AML) in two. All six showed an abnormal karyotype, in four of them highly characteristic of therapy-related MDS (t-MDS) and therapy-related AML (t-AML). The cumulative risk of t-MDS and t-AML increased from 16 months after start of the primary chemotherapy for lymphoma and reached 17.3% (s.e. 8.5%) after 74 months. If calculated from start of BEAM and ASCT, the cumulative risk increased as early as 4 months and reached 24.3% (s.e. 12.9%) after 43 months. For the whole course of the disease, the relative risk (RR) of AML was 357 (95% CI: 43-1290), as two overt leukemias were observed vs 0.0056 expected cases of de novo AML. In the present cohort the risk of t-MDS and t-AML although high, did not differ from our previous experience in patients treated conventionally for Hodgkin's disease and non-Hodgkin lymphomas, and did not differ for patients receiving stem cells isolated from the bone marrow as compared to patients receiving stem cells isolated from peripheral blood. Antecedent chemotherapy seems to be the critical factor for the development of t-MDS and t-AML rather than the BEAM and ASCT regimen, which however may accelerate the evolution of the disease.

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Myelodysplastic Syndromes; Neoplasms, Second Primary; Podophyllotoxin; Risk Factors

Few data are available on the cost, safety, and long-term efficacy of single-agent high-dose melphalan (HDM) followed by autologous bone marrow (ABMT) or blood stem cell (ABSCT) transplantation in the salvage therapy of Hodgkin's disease (HD).. From February 1981 to September 1996, 23 patients with relapsed (n = 15) or refractory (n = 8) HD received salvage therapy with HDM 140-200 mg/m2 followed by non-cryopreserved ABMT (n = 18) or cryopreserved ABSCT (n = 5). The cost of HDM/ABSCT in 1996, from initial consultation until transfer back to referring physician, was determined and compared to the estimate costs of two multi-agent regimens commonly used for HD.. HDM was well tolerated with no early transplant-related mortality. The five-year overall and progression-free survival rates were 52% and 50%, respectively. The average total cost in Canadian funds of HDM/ABSCT in 1996 was $34,400/patient. This cost was estimated to be $4,700-6,800 cheaper per patient than the multi-agent high-dose regimens.. These data suggest that HDM is safe, feasible, active, and reasonably inexpensive salvage therapy for patients with relapsed/refractory HD.

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Bone Marrow Transplantation; Combined Modality Therapy; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged

A randomised trial comparing filgrastim-mobilised peripheral blood progenitor cell (PBPC) transplants with autologous bone marrow transplantation (ABMT) for haematopoietic stem cell support has not been done. We compared the effects of filgrastim-mobilised PBPC or autologous bone marrow reinfused to lymphoma patients after high-dose chemotherapy in a prospective randomised multicentre trial.. The trial was done at six centres in three European countries. After high-dose chemotherapy (carmustine, etoposide, cytarabine, and melphalan [BEAM protocol]) 58 patients with advanced Hodgkin's disease or high-grade non-Hodgkin lymphoma received either filgrastim-mobilised PBPC (n = 27) or bone marrow (n = 31) for haemopoietic reconstitution.. The median number of days with platelet transfusions after grafting was 6 in the PBPC transplantation group and 10 in the ABMT group (estimate of treatment difference 5 days, 95% CI 3-7 days). Time to platelet recovery above 20 x 10(9)/L was 16 days in the PBPC transplantation group and 23 days in the ABMT group (p = 0.02). Time to neutrophil recovery above 0.5 x 10(9)/L was also reduced in the PBPC transplantation group (11 vs 14 days, p = 0.005). Patients randomised to PBPC transplantation needed fewer red blood cell transfusions (two vs three, p = 0.002) and spent less time in hospital (17 vs 23 days, p = 0.002). Early post-transplant morbidity and mortality as well as overall survival (median follow-up 311 days) were similar in both groups. There was no notable toxicity ascribed to filgrastim administration or the leucapheresis procedures.. In patients with lymphoma treated with high-dose chemotherapy, reinfusing filgrastim-mobilised PBPC instead of autologous bone marrow significantly reduced the number of platelet transfusions, the time to platelet and neutrophil recovery, and led to earlier discharge from hospital.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cytarabine; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leukocytes, Mononuclear; Lymphoma, Non-Hodgkin; Male; Melphalan; Platelet Transfusion; Podophyllotoxin; Prospective Studies; Recombinant Proteins; Survival Analysis; Time Factors; Transplantation, Autologous

Forty-two patients with relapsed or refractory Hodgkin's disease (HD) were treated with high-dose chemotherapy (BEAM regimen) followed by autologous bone marrow and/or peripheral blood progenitor cell (PBPC) rescue. There was one procedure-related death and the overall response rate at 6 months was 88% (95% confidence interval 78-98%). The 2 year overall and event-free survival was 81% (95% confidence interval 65-96%) and 74% (95% confidence interval 58-89%) respectively. Median follow-up was 33 months. The use of PBPC instead of marrow resulted in a significant shortening of the time to engraftment (P < 0.01). Multivariate analysis identified the pre-transplant LDH level as a highly significant factor in predicting overall survival (P = 0.007). The BEAM regimen is an effective conditioning schedule that is well tolerated but patients with a raised LDH at the time of transplant remain at high risk of early relapse and death due to disease.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cytarabine; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; L-Lactate Dehydrogenase; Male; Melphalan; Middle Aged; Podophyllotoxin; Prognosis; Recurrence; Survival Rate; Transplantation, Autologous; Treatment Outcome

The objectives of this study were to compare the costs of managing lymphoma patients who underwent mini-BEAM salvage chemotherapy with G-CSF prophylactic support against a group of similar patients without growth factors. Methods used included: 1) A retrospective chart review was conducted to estimate the average length of hospitalization and resource consumption for the management of fever and neutropenia in the two groups of patients and 2) An economic analysis was then performed from a hospital perspective which considered only institutional resource utilization. Costs of antibiotic support and monitoring, lab tests as well as G-CSF were calculated. Results demonstrated that overall, patients who received prophylactic G-CSF after chemotherapy required 2 fewer hospital days compared to controls. The administration of G-CSF resulted in a savings of approximately $1580/patient relative to control. When the initial G-CSF expenditure was included in the analysis, the total net cost/patient was similar between the two groups. In conclusion, the results of the current study support the routine use of G-CSF in patients receiving salvage chemotherapy with mini-BEAM. The initial G-CSF expenditure would be offset by reduced hospitalization.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Fever; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Length of Stay; Lymphoma, Non-Hodgkin; Melphalan; Neutropenia; Retrospective Studies; Salvage Therapy

To evaluate the efficacy of carmustine (BCNU), etoposide, cytarabine (Ara-C), and melphalan (mini-BEAM) as salvage therapy in patients with relapsed or refractory Hodgkin's disease who were potentially eligible to undergo intensive therapy and autologous bone marrow transplantation (ABMT).. Forty-four patients with refractory or relapsed Hodgkin's disease after front-line combination chemotherapy referred for consideration of ABMT were treated with mini-BEAM (BCNU 60 mg/m2 on day 1, etoposide 75 mg/m2 on days 2 to 5, Ara-C 100 mg/m2 twice per day on days 2 to 5, and melphalan 30 mg/m2 on day 6) to maximum response. Eleven patients were refractory to primary chemotherapy. Twenty-three patients were treated in first relapse and 10 in second or subsequent relapse; 21 received mini-BEAM as their first salvage regimen. Patients were restaged to determine disease status immediately before intensive therapy and transplant.. The overall response rate was 84% (exact 95% confidence interval [CI], 70% to 92%), with a complete response (CR) rate of 32% (95% CI, 20% to 47%) and a partial response (PR) rate of 52%. No treatment-related deaths were observed. Myelosuppression was the major toxicity. Almost all patients required platelet transfusions. Eighty-four percent were given RBC transfusions, and 54% required intravenous antibiotics for fever while neutropenic.. Mini-BEAM is a safe and effective regimen for treatment of refractory or relapsed Hodgkin's disease. Further studies are required to determine if responding patients have improved disease-free survival (DFS) after intensive therapy and ABMT.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Confidence Intervals; Critical Care; Cytarabine; Erythrocyte Transfusion; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Neutropenia; Platelet Transfusion; Podophyllotoxin; Preoperative Care; Prognosis; Recurrence; Salvage Therapy; Time Factors

Topics: Administration, Oral; Adult; Cryotherapy; Female; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mouth Mucosa; Multiple Myeloma; Prospective Studies; Stomatitis

A prospective phase II study was conducted to evaluate the efficacy of dexamethasone, carmustine, etoposide, cytarabine, and melphalan (Dexa-BEAM) as salvage chemotherapy for patients with Hodgkin's disease.. Fifty-five patients progressing on or relapsing after eight- or 10-drug chemotherapy (cyclophosphamide, vincristine, procarbazine, and prednisone plus doxorubicin, bleomycin, vinblastine, and dacarbazine [COPP+ABVD] or COPP+ABV+ifosfamide, methotrexate, etoposide, and prednisone [IMEP]) were treated with Dexa-BEAM. Patients who responded after two cycles of Dexa-BEAM either continued treatment for another two to three cycles or received high-dose chemotherapy/autologous bone marrow transplantation (HDCT/ABMT) with cyclophosphamide, etoposide, and carmustine (BCNU) (CVB) as conditioning regimen.. Seventeen patients (31%) achieved a complete remission and 16 (29%) a partial remission, resulting in a response rate of 60% (95% confidence interval, 46% to 73%). Progressive disease developed in 18 patients. Toxicity of Dexa-BEAM was acceptable with pronounced, but temporary World Health Organization (WHO) grade III/IV granulocytopenia and thrombocytopenia occurring in more than 90% of all courses. Two patients died of sepsis during granulocytopenia. Three prognostic subgroups could be distinguished: (1) patients progressing on initial chemotherapy, (2) patients relapsing within 12 months, and (3) patients with late relapses. The response rates for these groups were 52%, 60%, and 83%, and the median survival duration 12, 29, and 40+ months, respectively. In a nonrandomized comparison, the survival of patients who responded to two cycles of Dexa-BEAM and had additional cycles of Dexa-BEAM (n = 14) was not different from those responding patients who underwent HDCT/ABMT (n = 19). However, the power to detect a 20% survival difference was only 33% in this comparison.. Dexa-BEAM is an effective salvage treatment for patients with Hodgkin's disease who fail to respond to multidrug chemotherapy. Efficacy and toxicity are comparable to HDCT/ABMT and underline the need for prospective randomized trials to define better the role of HDCT with and without ABMT in these patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Dexamethasone; Etoposide; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Prospective Studies; Survival Analysis; Treatment Outcome

High-dose chemotherapy and radiotherapy with autologous bone-marrow transplantation (ABMT) are increasingly used for the treatment of relapsed and resistant Hodgkin's disease, although there has been no randomised trial of this treatment. The British National Lymphoma Investigation therefore undertook a randomised comparison of high-dose chemotherapy (BEAM = carmustine, etoposide, cytarabine, and melphalan) plus ABMT with the same drugs at lower doses not requiring bone-marrow rescue (mini-BEAM) in patients with active Hodgkin's disease, for whom conventional therapy had failed. 20 patients were assigned treatment with BEAM plus ABMT and 20 mini-BEAM. All have been followed up for at least 12 months (median 34 months). 5 BEAM recipients have died (2 from causes related to ABMT and 3 from disease progression) compared with 9 mini-BEAM recipients (all disease progression). This difference was not significant (p = 0.318). However, both event-free survival and progression-free survival showed significant differences in favour of BEAM plus ABMT (p = 0.025 and p = 0.005, respectively). Recruitment to the trial became increasingly difficult because patients refused randomisation and requested ABMT. It was therefore closed early (40 patients rather than 66 intended). Nevertheless, we found a dose-response effect in these patients with relapsed and resistant Hodgkin's disease. High doses facilitated by ABMT can lead to better disease-free survival.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cytarabine; Dose-Response Relationship, Drug; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Survival Rate

This study aimed to assess the safety and efficacy of using high dose melphalan and etoposide followed by autologous, non-cryopreserved marrow rescue in advanced Hodgkin's disease (HD). Seventeen patients with poor risk Hodgkin's disease from a single centre underwent autologous bone marrow transplant (ABMT) using high dose melphalan and etopside conditioning. Two patients had primary progressive resistant disease (PD), two were in fourth relapse, six in second or third complete remission (CR), one patient had good partial response (GPR) (> 75% reduction in initial bulk) to primary therapy and six were in first complete remission. The patients transplanted in first CR all has a Scotland and Newcastle Lymphoma Group (SNLG) Prognostic Index (Proctor et al., 1991) which indicated they were in a poor risk prognostic group. Melphalan and etoposide both have a short half life enabling ABMT to be accomplished using unmanipulated marrow stored at 4 degrees C. The marrow was returned to the patient within 56 h of harvest. Complete haematological reconstitution occurred in 16/17 patients, the rate of engraftment reflecting the amount of previous chemotherapy. One patient died of progressive Hodgkin's disease before full engraftment could occur. In patients autografted in first remission, the median number of days with neutropenia (< 0.5 x 10(9) l-1 neutrophils) was 19 (range 9-33) and, in those in subsequent remission, 27 days (range 18-36). The median number of days to 50 x 10(9) l-1 platelets in the same groups were 29 (21-80) and 50 (41-74) respectively. The number of days in hospital post transplant in both groups was similar; median 22 (15-27) and 23 (17-37) respectively. There were no procedural deaths and none of the patients transplanted in first, second or third CR have relapsed (median follow up 21 months). The two patients transplanted with progressive disease showed only temporary responses. The two patients transplanted in fourth relapse went into CR; one is still alive and in CR 15 months post transplant, but the other relapsed 18 months post transplant. This form of intensification therapy with marrow rescue has been shown to be effective and of low toxicity and now forms part of a randomised controlled trial in poor risk Hodgkin's patients as identified by the SNLG index (Proctor et al., 1992).

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Dose-Response Relationship, Drug; Etoposide; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Risk Factors; Transplantation, Autologous

Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarial overall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses > 10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the r

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cytarabine; Etoposide; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Prognosis; Risk; Survival Rate; Transplantation, Autologous

Fourteen patients with relapsed Hodgkin's disease responded to a salvage therapy with Dexa-BEAM (dexamethasone, BCNU, etoposide, Ara-C and melphalan). In seven patients a continuous i.v. infusion with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was started subsequent to Dexa-BEAM (+rhGM-CSF) while the other seven patients received no hemopoietic growth factor (-rhGM-CSF). It was our objective to study the impact of rhGM-CSF on the collection of blood-derived hemopoietic stem cells in patients with extensive prior chemo- and radiotherapy not eligible for marrow harvest. Compared to baseline, we observed a significant increase of colony-forming units granulocyte-macrophage (CFU-GM) in the peripheral blood of patients receiving rhGM-CSF (p less than 0.05). On average, the yield of total nucleated cells and CFU-GM collected per single leukapheresis was 2.2 and 2.4-fold higher in the rhGM-CSF-treated patients respectively (p less than 0.05). With rhGM-CSF the interval from the start of chemotherapy to the end of blood stem cell collection could be reduced by 6 days (p less than 0.05). Following the CBV pretransplant regimen (cyclophosphamide, BCNU, etoposide), the reinfusion of rhGM-CSF-exposed stem cells resulted in a shorter time of leukocyte recovery (p less than 0.05). The number of CFU-GM/kg body weight transplanted was found to be predictive for the time of neutrophil recovery (p less than 0.05). In patients with bone marrow hypoplasia or fibrosis, rhGM-CSF as part of an effective salvage therapy improves the collection of blood stem cells that are capable of restoring hemopoiesis after high-dose pretransplant therapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Dexamethasone; Etoposide; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leukapheresis; Male; Melphalan; Middle Aged; Recombinant Proteins; Recurrence; Transplantation, Autologous

This report describes the efficacy and toxicity of PAVe (procarbazine, Alkeran, vinblastine) and irradiation (RT) in the management of 159 patients with locally extensive or advanced stage Hodgkin's disease (HD) at Stanford University. Patients received six courses of chemotherapy alternating with RT. The extent of RT and the schedule of treatment varied according to the stage of disease. About 2/3 of patients received PAVe/RT in the setting of prospective, randomized clinical trials. The rate of complete response was 93%. With a median follow-up of seven years (range 2-17), the 15 year actuarial freedom from progression (FFP) is 78% and overall survival is 75%. Ten-year FFP by stage is: 80% for locally extensive stage II, 90% for stage IIIA and 70% for stage IIIB. Excellent and equal results were attained with PAVe/RT vs. MOP(P) (mustard, Oncovin, procarbazine with or without prednisone)/RT in the randomized combined modality studies. Progression or recurrence was documented in 30 patients and was more common in irradiated sites. PAVe was well tolerated acutely. There were no treatment related fatalities. Twenty-three (14%) patients were admitted to the hospital for neutropenic fever. Five second malignancies have occurred after PAVe/RT only: one myelodysplastic syndrome, one acute myelogenous leukemia, one non-Hodgkin's lymphoma and two solid tumors including a case of non-small cell lung cancer and an in situ carcinoma of the cervix. Three patients died from myocardial infarction several years after the completion of treatment. These mature data show that PAVe/RT is effective and well-tolerated therapy for locally extensive stage II and IIIA/B HD.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Combined Chemotherapy Protocols; Cause of Death; Combined Modality Therapy; Follow-Up Studies; Hodgkin Disease; Humans; Melphalan; Neoplasm Recurrence, Local; Neoplasm Staging; Procarbazine; Prospective Studies; Radiotherapy Dosage; Survival Rate; Vinblastine

The initial promising results with alternating chemotherapy regimens (mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine [MOPP/ABVD]; lomustine, melphalan, and vindesine [CAD] plus MOPP plus ABV) combined with intermediate-dose radiation therapy (RT) have been sustained with further follow-up; 82.2% of patients (152 of 185) achieved a complete remission (CR), and overall survival is 71.7% +/- 4.4% at 8 years (median follow-up is 55 months among the survivors). No statistically significant differences were found in CR percentage, CR duration, or survival between stages IIB, IIIB, and IV patients. For that reason, stepwise Cox regression analyses to identify the important prognostic factors were performed on overall survival, tumor mortality, freedom from disease progression, and survival following disease progression. Pretreatment characteristics were also tested for association with the probability of achieving CR, CR duration, and death due to other causes. Characteristics that were consistently associated with an independently unfavorable prognosis were low hematocrit, high serum lactic acid dehydrogenase (LDH), age more than 45 years, inguinal node involvement, mediastinal mass greater than .45 of the thoracic diameter, and bone marrow involvement. Patients with two or more unfavorable characteristics were much more likely to fail treatment (median survival, 62.4 months) than those with none or only one unfavorable factor (greater than 95% survival). This striking difference between the low- and high-risk groups remained even if the comparison was restricted to patients less than or equal to 45 years of age. These results provide a basis for selecting the young patients at high risk of failure for more intensive initial treatment with either autologous bone marrow rescue or hematopoietic growth factors.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Doxorubicin; Female; Hematocrit; Hodgkin Disease; Humans; Lomustine; Lymphatic Metastasis; Male; Mechlorethamine; Melphalan; Middle Aged; Models, Biological; Neoplasm Staging; Prednisone; Procarbazine; Prognosis; Remission Induction; Survival Analysis; Vinblastine; Vincristine; Vindesine

MOPP chemotherapy was the significant breakthrough that improved the outlook for patients with advanced Hodgkin's disease. Results with alternating potentially non-cross-resistant drug combinations, including MOPP/ABVD, CAD/MOPP/ABV, and MOPP/ABV, are similar and seem to be slightly superior to those with MOPP alone. Limited adjuvant RT does not seem to add appreciably to the morbidity of chemotherapy, although its role in improving on results with chemotherapy alone has not been well studied in prospective, randomized, controlled clinical trials. There are two major challenges for the future. The first is to improve the outcome for advanced Hodgkin's disease patients, perhaps with more intensive chemotherapy and RT with use of cytokines such as the colony-stimulating factors or interleukin-1 or with rescue employing autologous bone marrow transplantation or both. The second challenge is to reduce the morbidity but not the effectiveness of treatment for advanced Hodgkin's disease patients without adverse prognostic factors.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Combined Modality Therapy; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; Leukemia; Lomustine; Lymphoma; Male; Mechlorethamine; Melphalan; Middle Aged; Neoplasms, Multiple Primary; Prednisone; Procarbazine; Remission Induction; Vinblastine; Vincristine; Vindesine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Dacarbazine; Doxorubicin; Hodgkin Disease; Humans; Lomustine; Mechlorethamine; Melphalan; Middle Aged; Prednisone; Procarbazine; Randomized Controlled Trials as Topic; Vinblastine; Vincristine; Vindesine

Thirty-one patients with resistant Hodgkin's disease were treated by an identical high dose chemotherapy regimen and autologous bone marrow transplantation. Twelve of these patients received recombinant human granulocyte/macrophage colony stimulating factor (rh GM-CSF) in a phase I/II study. rh GM-CSF was administered by continuous infusion into an indwelling central venous catheter for 3-21 days at doses of 100-400 micrograms/m2/day. The patients receiving rh GM-CSF did not differ significantly from those who did not receive growth factor with regard to age, previous therapy or number of bone marrow cells infused. rh GM-CSF resulted in more rapid neutrophil regeneration, the average time to achieve a neutrophil count of greater than or equal to 0.5 x 10(9)/l being 17.5 days compared to 24.9 days in the control group (p less than 0.01). Platelet recovery was very varied and not accelerated by rh GM-CSF. Patients receiving rh GM-CSF had a similar infection rate (58% vs 68% in the control group), similar number of febrile days (5.0 vs 4.7 days) and similar period of hospitalization to the control group (30.1 vs 30.2 days). Randomized controlled trials are now required to define the clinical value of rh GM-CSF in the setting of autologous bone marrow transplantation.

Topics: Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Colony-Stimulating Factors; Combined Modality Therapy; Cytarabine; Drug Evaluation; Etoposide; Granulocytes; Hodgkin Disease; Humans; Leukocyte Count; Macrophages; Melphalan; Neutropenia; Neutrophils; Postoperative Complications; Recombinant Proteins; Transplantation, Autologous

In a significant fraction of patients with Hodgkin's disease, a condition develops that is resistant to conventional chemotherapy. Experience using high-dose chemotherapy, with or without TBI, and ABMR is expanding. In Hodgkin's disease, remissions can be achieved in approximately half of the patients with relapsed advanced disease. High-dose chemoradiotherapy regimens are toxic and require extensive supportive care. Relapse frequently occurs in areas of previous disease, which suggests failure of the conditioning regimen rather than infusion of occult tumor cells in the autologous bone marrow. Thus, the role of marrow purging in this therapy needs to be evaluated further. It is also important to evaluate the effects of more vigorous attempts at cytoreduction of bulky disease prior to high-dose therapy and ABMR. We recommend that high-dose therapy and ABMR in an investigational setting be used in patients with Hodgkin's disease who experience relapse after MOPP and ABVD or equivalent regimens. Toxicity can be decreased and efficacy increased only if therapy is administered to patients who have not been heavily pretreated and who have lower tumor burden and a good performance status. Finally, high-dose therapy with ABMR has a definite role in salvaging patients with refractory Hodgkin's disease. Many issues need to be resolved, including the optimal timing of this approach and the optimal conditioning regimen. In the years to come these questions may be answered by the many studies now under way.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Dose-Response Relationship, Drug; Hodgkin Disease; Humans; Melphalan; Remission Induction; Transplantation, Autologous; Whole-Body Irradiation

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Drug Evaluation; Drug Resistance; Etoposide; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Melphalan; Neoplasm Recurrence, Local; Neoplasms; Thioguanine; Transplantation, Autologous

From January 1979 to June 1983, 71 evaluable, previously untreated patients with advanced Hodgkin's disease completed a randomized trial of two or three potentially non-cross-resistant drug combinations and low-dose radiotherapy to initially involved nodal regions (2,000 to 3,000 rads). All patients received nine cycles of alternating chemotherapy regimens and radiotherapy between cycles 6 and 7. Thirty-four patients received three combinations: lomustine, melphalan, vindesine (CAD), MOPP, and doxorubicin, bleomycin, vinblastine (ABV). The complete remission rate was 82 percent, partial remission rate 12 percent, and progression rate 6 percent. There were two relapses from complete remission and three deaths. Thirty-seven patients received MOPP and ABV plus dacarbazine (D). The complete remission rate was 78 percent, partial remission rate 16 percent, and progression rate 6 percent, with three relapses from complete remission and five deaths. Myelosuppression was more frequent with CAD/MOPP/ABV/radiotherapy, and nausea and vomiting with MOPP/ABVD/radiotherapy. The results for both are among the best reported, and CAD/MOPP/ABV/radiotherapy was more acceptable to patients.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Combined Modality Therapy; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; Lomustine; Male; Mechlorethamine; Melphalan; Middle Aged; Prednisone; Procarbazine; Vinblastine; Vincristine; Vindesine

Topics: Adolescent; Adult; Antineoplastic Agents; Bone Marrow; Clinical Trials as Topic; Drug Therapy, Combination; Female; Hodgkin Disease; Humans; Male; Mechlorethamine; Melphalan; Middle Aged; Prednisone; Procarbazine; Remission, Spontaneous; Vinblastine; Vincristine

Topics: Amyloid; Amyloidosis; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Cyclophosphamide; Hodgkin Disease; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infections; Leukemia, Lymphoid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Prognosis; Pyelonephritis

Autologous stem cell transplantation (ASCT) remains a cornerstone in the treatment of both Hodgkin lymphoma (HL) and various non-Hodgkin lymphoma (NHL) subtypes. BEAM (carmustine, etoposide, cytarabine, and melphalan) is the most frequently used conditioning regimen; however, owing due to limited availability and toxicity of carmustine, thiotepa-containing regimens have been suggested. We previously reported encouraging results in ASCT with a TECAM (thiotepa, etoposide, cyclophosphamide, cytarabine, and melphalan) conditioning regimen from 2000 to 2013. We aimed to update our experience with the TECAM regimen by adding our experience from 2013 to 2020 to the previously reported cohort. Moreover, we aimed to use the detailed data for the 2 transplant cohorts to identify improvements in ASCT outcomes in the recent era. We retrospectively analyzed all lymphoma patients who underwent ASCT at our center between January 2000 and December 2020. A total of 353 lymphoma patients were included (142 in the newer cohort added to 211 previously reported patients), all of whom were treated with our standard TECAM conditioning regimen. The cohort included 127 patients with HL, 107 with DLBCL, and 119 with other NHL subtypes. The newer cohort was characterized by significantly poorer Eastern Cooperative Oncology Group Performance Status (ECOG-PS) prior to ASCT (45.7% versus 19.3% with ECOG-PS ≥1; P < .01), whereas a higher proportion of patients entered transplantation in complete response (CR) (71.9% versus 47.8%; P < .01). The median follow-up after ASCT was 136.4 months (95% confidence interval [CI], 91.4 to 181.4 months). The 3-year progression-free survival (PFS) and overall survival (OS) rates post-ASCT for the entire cohort were 59.8% and 79.3%, respectively. Evaluating the 303 of 353 patients (86.4%) who entered ASCT with a responsive disease-a population that represents today's approach to the selection of patients for ASCT-the 3-year PFS and OS rates were 61.5% and 81.9%, respectively. In this population, the 3-year PFS rate was 62.2% for HL, 62.6% for DLBCL, 64.3% for primary central nervous system lymphoma (PCNSL), and the 3-year OS rate were 90.1%, 75.2%, and 78.6%, respectively. OS was significantly better in the newer cohort (P < .01), but not when evaluating only patients who entered ASCT with responsive disease. Dose reductions, poor disease status, and poor ECOG-PS at ASCT entry were associated with worse outcomes across all lymphoma subtypes. In accord

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Melphalan; Retrospective Studies; Thiotepa; Transplantation, Autologous

Neutropenia postchemotherapy is associated with favorable outcomes, which was attributed to optimal dosing. However, little is known about the neutrophil decline rate as a predictor of cancer outcomes, which may reflect a dynamic marker of chemosensitivity. We assessed the association between the neutrophil decline rate and disease outcomes in a known cohort of 212 lymphoma patients, treated with thiotepa, etoposide, cyclophosphamide, cytarabine, and melphalan (TECAM) conditioning followed by autologous transplant in our center between 2000 and 2013. Slower neutrophil decline rate was correlated with worse overall survival, mediated not by shorter time to progression (TTP), but rather by worse survival post-progression, possibly pointing to chemosensitivity at each line of therapy as the responsible mechanism. The effect was seen across histologies and was independent of stronger predictors of outcome like performance status (PS) and response before transplant. Prospective research is needed to confirm our results and expand their validity to other clinical scenarios.

Topics: Antineoplastic Combined Chemotherapy Protocols; Autografts; Cytarabine; Etoposide; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Melphalan; Neoplasm Recurrence, Local; Neutrophils; Prospective Studies; Transplantation Conditioning; Transplantation, Autologous

While high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) leads to improved disease-free survival (DFS) for children and adults with relapsed/refractory Hodgkin lymphoma (HL), relapse remains the most frequent cause of mortality post-transplant. Rituximab has been successfully incorporated into regimens for other B-cell lymphomas, yet there have been limited studies of rituximab in HL patients. We hypothesized that adding rituximab to BEAM (carmustine, etoposide, cytarabine, melphalan) conditioning would reduce relapse risk in HL patients post-transplant. Here, we retrospectively review the outcomes of patients with relapsed/refractory HL who received rituximab in addition to BEAM. The primary outcome was DFS. Our cohort included 96 patients with a median age of 28 years (range, 6-76). Majority of patients (57%) were diagnosed with advanced (Stage III-IV) disease, and 62% were PET negative pre-transplant. DFS was 91.5% at 1 year [95% CI 86-98%], and 78% at 3 years [95% CI 68-88%]. NRM was 0% and 3.5% at 1-year [95% CI 0-3%] and 3-years [95% CI 0-8.5%], respectively. 25% of patients developed delayed neutropenia, with 7% requiring infection-related hospitalizations, and one death. We have demonstrated excellent outcomes for patients receiving rituximab with BEAM conditioning for relapsed/refractory HL. Future comparative studies are needed to better determine whether rituximab augments outcomes post-transplant.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Cytarabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Rituximab; Transplantation Conditioning; Transplantation, Autologous; Young Adult

Reduced-intensity conditioning (RIC) allogeneic haematopoietic cell transplantation (allo-HCT) is a curative option for select relapsed/refractory Hodgkin lymphoma (HL) patients; however, there are sparse data to support superiority of any particular conditioning regimen. We analyzed 492 adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for HL between 2008 and 2016, utilizing RIC with either fludarabine/busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) or fludarabine/cyclophosphamide (Flu/Cy). Multivariable regression analysis was performed using a significance level of <0·01. There were no significant differences between regimens in risk for non-relapse mortality (NRM) (P = 0·54), relapse/progression (P = 0·02) or progression-free survival (PFS) (P = 0·14). Flu/Cy conditioning was associated with decreased risk of mortality in the first 11 months after allo-HCT (HR = 0·28; 95% CI = 0·10-0·73; P = 0·009), but beyond 11 months post allo-HCT it was associated with a significantly higher risk of mortality, (HR = 2·46; 95% CI = 0·1.32-4·61; P = 0·005). Four-year adjusted overall survival (OS) was similar across regimens at 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy (P = 0·64), respectively. These data confirm the choice of RIC for allo-HCT in HL does not influence risk of relapse, NRM or PFS. Although no OS benefit was seen between Flu/Bu and Flu/Mel 140; Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT (possibly due to late NRM events).

Topics: Adolescent; Adult; Aged; Allografts; Busulfan; Cause of Death; Comorbidity; Cyclophosphamide; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Myeloablative Agonists; Progression-Free Survival; Recurrence; Siblings; Transplantation Conditioning; Unrelated Donors; Vidarabine; Young Adult

BACKGROUND High-dose chemotherapy followed by autologous hematopoietic stem cell transplant has proven useful in relapsed or refractory cases of Hodgkin and non-Hodgkin lymphoma. BEAM (carmustine, etoposide, cytarabine, melphalan) is frequently used as a conditioning regimen; however, the high cost and limited availability of BCNU hinders its use in Mexico. MATERIAL AND METHODS Between January 2013 and February 2019, refractory or relapsing HL and NHL patients were treated with an autologous HSCT conditioned with cisplatin+dexamethasone as substitution for BCNU in BEAM. RESULTS Four HL patients and 6 NHL patients were included; 60% were male, the average age was 34.5±15.2 years, the median follow-up was 19.1 months, and 70% had a complete response after transplant. OS at 12 months was 63% for NHL and 100% for HL. Time to hematological recovery was 17.6±2.8 days; all patients developed grade III/IV neutropenia and thrombocytopenia, and 8 patients had transplant-related infections. CONCLUSIONS This retrospective study based on real-world data introduces the option of substituting carmustine with cisplatin+dexamethasone, with a similar response, expected lower cost, and better accessibility in developing nations.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Combined Modality Therapy; Cytarabine; Dexamethasone; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Pilot Projects; Podophyllotoxin; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous; Young Adult

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Recurrence; Transplantation Conditioning; Transplantation, Autologous; Young Adult

High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (AHSCT) is a standard of care for patients with relapsed Hodgkin lymphoma. Different conditioning regimens before AHSCT have been used, with the 2 most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide). We retrospectively compared the outcomes of patients treated with BEAM (n = 128) or BUCYVP16 (n = 105) followed by AHSCT. After a median follow-up of 4.2 years for BEAM and 3.8 for BUCYVP16 from AHSCT, the 5-year cumulative incidence of relapse was 29% with BEAM compared with 56% with BUCYVP16 (P < .001). Median progression free survival (PFS) and overall survival (OS) were not reached with BEAM and were 2.0 and 7.8 years with BUCYVP16, respectively. Improved PFS (P < .001) and OS (P = .001) were observed with BEAM for patients who needed transplant within 24 months from diagnosis and for patients not in complete remission (non-CR; P = .001 and P < .001, respectively) at AHSCT. In this large retrospective comparison the use of BEAM conditioning before AHSCT resulted in a statistically significant improved PFS and OS and lower relapse compared with BUCYVP16. This supports the use of BEAM as a frontline conditioning regimen before AHSCT for early relapsed and non-CR Hodgkin lymphoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Podophyllotoxin; Transplantation Conditioning; Young Adult

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Carmustine; Case-Control Studies; Cytarabine; Diarrhea; Disease-Free Survival; Drug Resistance, Neoplasm; Etoposide; Female; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Autologous; Young Adult

Hodgkin lymphoma (HL) patients failing after high dose chemotherapy (HDC) and auto-SCT have a poor outcome. Some patients may still benefit from further treatments. From 1996 to 2016, 137 HL patients (39.5%) out of 347 transplanted experienced post auto-SCT failure. Males/female 61%:39%, median age at auto-SCT 23.4 years and median follow-up 55.6 months (9-153). Type of failure was progressive (46%), relapsed (35%) or persistent disease/refractory disease (19%). Median overall survival (OS) from the time of failure is 20 months; 35 patients (25.5%) are alive. One hundred and four patients received treatment; the response rate was 45%; complete remission in 41 (30%) and partial remission in 21 (15%) patients. 1st interventions post auto-SCT were chemotherapy (39%), radiation therapy (35%) or best supportive care (24%). Twenty-seven patients with 2nd-SCT (allogeneic (15), auto-SCT (2)) and/or brentuximab (18 patients) had superior OS (50.6 months) vs other treatments (22.5 months, P value 0.037). COX regression multivariate analysis identified post auto-SCT treatment failure before 12 months (hazard ratio (HR) 3.37, CI 1.7-6.6, P value < 0.001), presence of B symptoms (HR 2.55, CI 1.4-4.6, P value 0.002), stages III-IV (HR 2.7, CI 1.5-4.9, P value 0.001), albumin < 4 g/dl (HR 1.76, CI 1.1-2.9, P value 0.027) and tumor > 5 cm (HR 1.1.9, CI 1.13-3.25, P value 0.015) as significant risk factors; P value < 0.001. KM OS with 0-1 factor (148.6 months): 2 factors (23.6 months) and 3-5 factors (9.4 months) (P value < 0.001). OS was 63%:25%:7% respectively with 0-1:2:3-5 factors respectively (P value < 0.001). Despite high-risk factors, 2nd-SCT/brentuximab use post HDC auto-SCT failure may result in durable survival.

Topics: Adolescent; Adult; Allografts; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Brentuximab Vedotin; Carmustine; Cisplatin; Combined Modality Therapy; Cytarabine; Dacarbazine; Disease-Free Survival; Doxorubicin; Drug Resistance, Neoplasm; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunoconjugates; Kaplan-Meier Estimate; Male; Melphalan; Methylprednisolone; Middle Aged; Proportional Hazards Models; Remission Induction; Retrospective Studies; Salvage Therapy; Transplantation Conditioning; Transplantation, Autologous; Vinblastine; Young Adult

High-dose chemotherapy and autologous stem cell transplantation (ASCT) is the current standard of care for relapsed non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Conditioning regimens with high-dose carmustine have been associated with idiopathic pneumonitis syndrome. We, therefore, created a modified alternative TECAM conditioning regimen, consisting of etoposide, thiotepa, cytarabine, cyclophosphamide, and melphalan.. We retrospectively analyzed our cohort of 212 NHL and HL patients, who had undergone ASCT with the TECAM conditioning regimen from 2000 to 2013. Although toxicity and engraftment were analyzed for all 212 patients, the survival analysis was performed for the 2 largest groups of patients, those with diffuse large B-cell lymphoma (DLBCL) and those with HL (n = 127) to minimize heterogeneity.. The 3-year overall survival among the DLBCL and HL patients was 0.618 (95% confidence interval [CI], 0.490-0.722) and 0.828 (95% CI, 0.701-0.904), respectively. Stage IV disease at transplantation was a statistically significant poor prognostic factor. Higher Eastern Cooperative Oncology Group performance status and progressive disease at transplantation were found to be borderline significant. No idiopathic pneumonitis syndrome cases were reported in our cohort. Six patients died of treatment-related toxicity during the first 100 days. The 3-year progression-free survival was 0.5 (95% CI, 0.37-0.61) for HL patients and 0.49 (95% CI, 0.36-0.60) for DLBCL patients.. Our results are encouraging and justify evaluation of TECAM versus BEAM (carmustine, etoposide, cytarabine, melphalan) in a prospective multicenter study in a large homogenous patient population.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Pneumonia; Retrospective Studies; Thiotepa; Transplantation Conditioning; Transplantation, Autologous; Young Adult

Previous studies in adults have shown that peripheral blood absolute lymphocyte and monocyte count ratio (ALC/AMC) after autologous stem cell transplantation (ASCT) can predict outcome in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). We retrospectively reviewed all of our children, adolescent, and young adult (CAYA) patients (age ≤26) who underwent transplantation for R/R HL between 2004 and 2015. Seventy-six patients (median age, 21; range, 10 to 26 years) who reached day 100 disease free were analyzed; 33% of them had positron emission tomography (PET)-positive tumors before ASCT. Patients received high-dose carmustine, etoposide, cytarabine, and melphalan (n = 40) or gemcitabine/busulfan/melphalan (n = 36). Median follow-up after day 100 was 3.9 years (95% confidence interval [CI], 2.8 to 4.9). A day 100 ALC/AMC ratio >2.1 correlated with lower risk of relapse (hazard ratio,  .097; 95% CI, .03 to .29; P <.0001). Patients with day 100 ALC/AMC ratios >2.1 and ≤2.1 had 4-year relapse-free survival rates of 93% and 33%, respectively (P = .0001) and 4-year overall survival rates of 96% and 76%, respectively (P = .0001). In addition, an ALC/AMC ratio increase >1.8 from day 15 to day 100 correlated with lower risk of relapse (hazard ratio, .24; 95% CI, .08 to 0.73; P = .01). Likewise, an ALC/AMC ratio change >.26 from day 30 to day 100 also correlated with a lower likelihood of relapse (hazard ratio, .20; 95% CI,  .081 to .51; P = .0007). Multivariate analysis showed that a positive PET scan at ASCT, day 100 ALC/AMC ratio ≤ 2.1, and an ALC/AMC ratio change either ≤1.8 from day 15 to day 100 or ≤.26 from day 30 to day 100 were independent adverse predictors. In conclusion, our analysis confirms in CAYA patients prior observations in adults indicating a major prognostic effect of peripheral lymphocyte and monocyte counts at day 100 and earlier post-ASCT time points in R/R HL.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Autografts; Busulfan; Child; Deoxycytidine; Disease-Free Survival; Female; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphocyte Count; Male; Melphalan; Recurrence; Retrospective Studies; Young Adult

An adult woman developed polymorphic post-transplant lymphoproliferative disorder (PTLD) 58 months after unrelated cord blood transplantation. She was treated successfully with chemotherapy and radiation therapy but presented with lymphadenopathy and splenomegaly 74 months after transplantation. A lymph node biopsy confirmed the diagnosis of nodular sclerosis type Hodgkin lymphoma (classical Hodgkin lymphoma [CHL]-type PTLD). After salvage therapy and hematopoietic stem cell harvesting, she was subsequently treated with consolidative high-dose chemotherapy with melphalan followed by stem cell rescue, which resulted in durable remission. High-dose chemotherapy using stem cell rescue has potential as a therapeutic option for subsequent CHL-type PTLD.

Topics: Female; Fetal Blood; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoproliferative Disorders; Melphalan; Middle Aged; Salvage Therapy

We report the recent isolation of Cryptococcus laurentii from the feces of a patient with Hodgkin's lymphoma who underwent autologous hematopoietic stem cell transplant (HSCT). The organism was identified using microscopic morphology, cultural characteristics, and biochemical tests including sugar assimilation. Minimum inhibitory concentration of various antifungals was determined by microbroth dilution method. The recovery of pure culture of C. laurentii from stool culture, and the patient's response to treatment with voriconazole support its potential etiological role. To the best of our knowledge, we report the first case of diarrhea caused by C. laurentii in an HSCT recipient.

Topics: Administration, Intravenous; Administration, Oral; Adult; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; C-Reactive Protein; Carmustine; Cryptococcosis; Cryptococcus; Cytarabine; Diarrhea; Etoposide; Feces; Fluconazole; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Melphalan; Microbial Sensitivity Tests; Transplantation Conditioning; Transplantation, Autologous; Voriconazole

Topics: Allografts; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Brentuximab Vedotin; Carmustine; Combined Modality Therapy; Cytarabine; Doxorubicin; Drug Resistance, Neoplasm; Etoposide; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunoconjugates; Lenalidomide; Liposomes; Male; Melphalan; Polyethylene Glycols; Recurrence; Remission Induction; Salvage Therapy; Thalidomide; Transplantation, Autologous; Young Adult

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHCT) is a well-defined treatment modality for relapsed/refractory non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). Although there are several options in terms of conditioning regimens before AHCT, no one treatment is accepted as a standard of care. This study aimed to compare different conditioning regimens for the treatment of NHL and HL.
. Medical records of 62 patients who had undergone AHCT following BEAM (BCNU, etoposide, cytarabine, and melphalan) and high-dose ICE (hICE; ifosfamide, carboplatin, and etoposide) conditioning regimens were analyzed retrospectively and compared in terms of efficacy and adverse effects.
 
. The study included a total of 29 and 33 patients diagnosed with relapsed/refractory NHL and HL, respectively. Patients received BEAM (n=37) or hICE (n=25) regimens for conditioning. One-year overall survival was 73±6% in all patients. One-year overall survival was 71±8% and 74±9% in the BEAM and hICE groups, respectively (p=0.86). The incidences of nausea/vomiting (grade ≥2) (84% vs. 44.7%; p=0.04) and mucositis (grade ≥2) (13% vs. 3%; p=0.002) were higher in the hICE group compared to the BEAM group. In addition, we witnessed significantly more hepatotoxicity of grade ≥2 (40% vs. 2.7%; p<0.005) and nephrotoxicity of grade ≥2 (48% vs. 2.7%; p<0.005) among patients who received hICE. Significantly more patients (n=4; 25%) in the hICE group experienced veno-occlusive disease (VOD) compared to the BEAM arm, where no patients developed VOD (p=0.01).. There was no difference in terms of overall survival between the BEAM and hICE groups. We observed significantly more adverse effects among patients treated with hICE. The BEAM regimen seems to be superior to hICE in terms of toxicity profile with comparable efficacy in patients with relapsed/refractory NHL and HL.. Amaç: Otolog kök hücre nakli (OKHN) destekli yüksek doz kemoterapi relaps/refrakter non-Hodgkin lenfoma (NHL) ve Hodgkin lenfoma (HL) tedavisinde uygulanan bir yöntemdir. Hazırlama rejimleri çok çeşitli olabilse de OKHN öncesinde henüz hiçbirisi standart olarak kabul edilmemiştir. Gereç ve Yöntemler: BEAM ve yüksek doz ICE (hICE) sonrasında OKHN olan 62 hastanın tıbbi kayıtları retrospektif olarak analiz edildi ve etkinlik ile yan etki profili açısından karşılaştırıldı. Bulgular: Çalışmaya toplamda 29 relaps/refrakter NHL ve 33 HL olgusu dahil edildi. Hazırlama rejimleri BEAM (n=37) ve hICE (n=25) idi. Bir yıllık genel sağkalım (GS) %73±%6 idi. BEAM ve hICE gruplarında ise 1 yıllık GS oranı sırasıyla %71±%8 ve %74±%9 olarak bulundu (p=0,86). Bulantı/kusma (derece ≥2) insidansı (%84 vs %44,7; p=0,04) ve mukozit (derece ≥2) insidansı (%13 vs %3; p=0,002) hICE grubunda daha yüksek oranda görüldü. İlaveten, hICE alan hastalarda istatistiksel olarak derece ≥2 hepatotoksisite (%40 vs %2,7; p<0,005) ve derece ≥2 nefrotoksisite (%48 vs %2,7; p<0,005) daha fazla oranda gözlendi. hICE grubunda veno-oklüzif hastalık (VOH) sıklığı (n=4; 25%) BEAM grubu ile karşılaştırıldığında istatistiksel olarak anlamlı düzeyde daha yüksekti (p=0,01). BEAM grubunda VOH görülmedi. Sonuç: GS oranları her iki grup arasında farklı bulunmadı ancak hICE grubunda anlamlı oranda yan etki sıklığı artmıştır. Relaps/refrakter NHL ve HL hastalarında benzer etkinlik ile BEAM rejimi toksisite profili açısından hICE rejiminden üstün olarak kabul edilebilir.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cytarabine; Dose-Response Relationship, Drug; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Recurrence; Retrospective Studies; Severity of Illness Index; Transplantation Conditioning; Transplantation, Autologous; Young Adult

High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose ((18) (F) FDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had (18) (F) FDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Drug Evaluation; Etoposide; Female; Graft Survival; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Nitrosourea Compounds; Organophosphorus Compounds; Positron-Emission Tomography; Prospective Studies; Registries; Salvage Therapy; Transplantation Conditioning; Treatment Outcome; Young Adult

We compared the lomustine, cytarabine, cyclophosphamide and etoposide (LACE) and BCNU, etoposide, cytarabine, melphalan (BEAM) conditioning regimens for toxicity, engraftment kinetics, and efficacy in 139 patients undergoing autologous hematopoietic stem cell transplant for primary refractory or relapsed lymphoma. Ninety-two patients with Hodgkin lymphoma and 47 with non-Hodgkin lymphoma were enrolled. Seventy-five patients received LACE while 64 received BEAM. The incidence of grade 3-4 oral mucositis (9 vs 38%; P < 0.001) and parenteral nutrition requirement (32 vs 69%; P < 0.001) were significantly lower in the LACE cohort. The median days to myeloid (10 vs 11; P = 0.007) and platelet engraftment (13 vs 15; P = 0.026) were shorter for the LACE cohort. Transplant-related mortality in the LACE group was 9% compared to 13% in patients treated with BEAM (P = NS). The probability of overall survival (OS) and progression-free survival (PFS) at 5 years for entire cohort was 46 and 41%, respectively. Probability of OS (LACE 46% vs BEAM 47%; P = NS) and PFS (LACE 37% vs BEAM 47%; P = NS) at 5 years was comparable between two groups. We conclude that LACE has better toxicity profile compared to BEAM and results in similar long-term survival in primary refractory or relapsed lymphoma transplant.

Topics: Adolescent; Adult; Autografts; Carmustine; Child; Child, Preschool; Cohort Studies; Cyclophosphamide; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lomustine; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multicenter Studies as Topic; Retrospective Studies; Survival Rate; Transplantation Conditioning; Young Adult

It was previously postulated that pretransplant myeloablative treatment may impair thymopoiesis, contributing in this way to delayed reconstitution of T cells after hematopoietic stem cell transplantation (HSCT). On the other hand, de novo generation of T cells after HSCT requires a competent thymus. Various myeloablative conditioning regimens (total body irradiation [TBI] or high-dose chemotherapy) routinely used in clinical practice may have potentially different impacts on the thymus. However, no comparative study on thymic output and T cell repertoire in autologous (auto)HSCT model has been presented so far. Here we evaluated thymic output and TCR diversity in 45 lymphoma patients submitted to autoHSCT differing in respect to conditioning regimen: high-dose chemotherapy as monotherapy (BEAM, n = 22) or combination of total body irradiation with cyclophosphamide chemotherapy: Cy/TBI (n = 23). Thymic output was assessed before and on days +100, +180, and +365 after autoHSCT by flow cytometric counts of recent thymic emigrant (RTE) cells (CD31(+) CD62L(+) CD45RA(+) CD4(+)) and quantification of signal joint TCR receptor excision circles (sjTRECs) by quantitative PCR. T cell repertoire diversity was analyzed on day +365 after autoHSCT by spectra-typing of the CDR3 region in the TCRVβ chain. The BEAM group, in contrast to the Cy/TBI group, manifested significantly higher proportions of RTE cells and sjTREC copy numbers on days +100 and +180. Analysis of TCRVβ spectra-types on day +365 revealed more restricted (monoclonal or oligoclonal) T cell repertoires in the Cy/TBI versus BEAM group (48.8% versus 18.2%, P = .0002). In conclusion, the conditioning scheme based on BEAM chemotherapy may be performed with lower risk of thymic destruction and T cell repertoire distortion than Cy/TBI scheme. This finding may help to potentially improve conditioning schemes to efficiently perform myeloablation and maintain active thymopoiesis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Autografts; Carmustine; Cyclophosphamide; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Podophyllotoxin; Thymus Gland; Transplantation Conditioning; Whole-Body Irradiation

Treatment of refractory Hodgkin disease deserves specific considerations. Recently, alemtuzumab-BEAM has been introduced in allogeneic hematopoietic stem cell transplantation (HSCT) in these patients.. We retrospectively analyzed the outcome of 20 patients with relapsed/refractory Hodgkin's lymphoma (HL) who received allogeneic HSCT following conditioning therapy with alemtuzumab-BEAM.. Treatment-related toxicity was tolerable. Half of the patients (50 %) had infections. Of these, 50 % were found to have pneumonia or catheter-related infections. In 20 %, an oral mucositis was observed. Acute graft-versus-host disease (GvHD) (≥grade 2) was seen in three patients. Complete remission (CR) could be achieved in 17 patients (85 %), 2 patients had persistent Hodgkin disease, and 1 patient died from infection prior to CR evaluation. Median progression-free survival and overall survival were 17.9 and 67.5 months, respectively. From the 17 CR patients, 8 had a relapse after a median of 10 months. Notably, of the eight patients relapsing after HSCT, all patients received another salvage treatment and four patients are still alive, whereas the other four patients died due to further progress. Six out of the remaining nine patients are still in CR, whereas the other three died from chronic GvHD and multi-organ failure. Overall, seven patients experienced chronic GvHD.. In summary, alemtuzumab-BEAM is a well-tolerated conditioning therapy for allogeneic HSCT with high response rates in refractory HL.

Topics: Adult; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Graft vs Host Disease; Hodgkin Disease; Humans; Male; Melphalan; Recurrence; Transplantation Conditioning; Young Adult

Forty patients (median age, 31 years; range, 20 to 63) with Hodgkin lymphoma underwent an allogeneic stem cell transplant with the gemcitabine-fludarabine-melphalan reduced-intensity conditioning regimen. Thirty-one patients (77%) had undergone a prior autologous stem cell transplant, with a median time to progression after transplant of 6 months (range, 1 to 68). Disease status at transplant was complete remission/complete remission, undetermined (n = 23; 57%), partial remission (n = 14; 35%), and other (n = 3; 8%). Twenty-six patients (65%) received brentuximab vedotin before allotransplant. The overall complete response rate before allotransplant was 65% in brentuximab-treated patients versus 42% in brentuximab-naive patients (P = .15). At the latest follow-up (October 2015) 31 patients were alive. The median follow-up was 41 months (range, 5 to 87). Transplant-related mortality rate at 3 years was 17%. Pulmonary, skin toxicities, and nausea were seen in 13 (33%), 11 (28%), and 37 (93%) patients, respectively. At 3 years, estimates for overall and progression-free survival were 75% (95% CI, 57% to 86%) and 54% (95% CI, 36% to 70%). Overall incidence for disease progression was 28% (95% CI, 16% to 50%). We believe the gemcitabine-fludarabine-melphalan regimen allows moderate dose intensification with acceptable morbidity and mortality. The inclusion of gemcitabine affected nausea, pulmonary, and likely skin toxicity. Exposure to brentuximab vedotin allowed more patients to reach allogeneic stem cell transplantation in complete remission. With over 50% of patients progression-free at 3 years, allogeneic stem cell transplantation with reduced-intensity conditioning remains an effective and relevant treatment option for Hodgkin lymphoma in the brentuximab vedotin era.

Topics: Adult; Brentuximab Vedotin; Deoxycytidine; Female; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunoconjugates; Lung Diseases; Male; Melphalan; Middle Aged; Nausea; Remission Induction; Salvage Therapy; Skin Diseases; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Young Adult

Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Hodgkin Disease; Humans; Male; Melphalan; Neoplasm Metastasis; Podophyllotoxin; Programmed Cell Death 1 Receptor; Remission Induction; Salvage Therapy

To assess the outcomes of overall survival and posttransplantation survival in patients with Hodgkin lymphoma (HL) undergoing autologous stem cell transplantation (ASCT) because of the development of relapse or resistance after chemotherapy (CT) or CT plus radiotherapy (combined modality treatment, CMT).. Forty-five patients undergoing ASCT because of the development of relapse or resistance after CT or CMT for HL were enrolled in the study. Radiotherapy was given as involved-field radiotherapy. Patients were treated with CT alone (n=25) or CMT (n=20). These 2 groups were further divided into 2 subgroups: the patients with early-stage (I to II) and advanced-stage (III to IV) HL.. Median patients age was 29 years (range, 16 to 60 y) and the median follow-up was 60 months (range, 12 to 172 mo). In the patients with advanced-stage HL, there was no statistically significant difference in overall survival between irradiated and nonirradiated patients (n=18, irradiated n=4 and nonirradiated n=14). However, in the patients with early-stage disease, there was a significant difference in 5- and 10-year overall survival between the irradiated and nonirradiated groups (81% vs. 48% and 66% vs. 24%, respectively, P=0.045; n=26, irradiated n=16 and nonirradiated n=10). In the univariate analysis, irradiated group and involvement of 1 to 2 nodal regions were found to be significant for overall survival, whereas irradiated group, early stage, and involvement of 1 to 2 nodal regions were found to be significant for posttransplantation survival. However, only irradiated group was found to be significant for posttransplantation survival in multivariate analysis (P<0.05).. Addition of involved-field radiotherapy to CT in patients undergoing ASCT after relapse or recurrence failed to provide survival benefit in patients with advanced HL, while a survival benefit was observed in patients with early-stage HL. Radiotherapy should be considered as part of CMT in the patients with early-stage HL, which should not be neglected.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Carmustine; Chemoradiotherapy; Cisplatin; Cohort Studies; Cytarabine; Dacarbazine; Dexamethasone; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Ifosfamide; Male; Mediastinal Neoplasms; Melphalan; Methylprednisolone; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Retrospective Studies; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome; Vinblastine; Young Adult

Persistence of disease after salvage therapy among relapsed or refractory Hodgkin lymphoma (HL) patients predicts poor outcome. Here, we report on 41 HL patients with active disease after salvage therapy and who received high-dose melphalan (HD-PAM) and auto-SCT as a bridge to a second autologous or an allogeneic transplantation between 2002 and 2013 at our center. Disease response was based on 18-fluoro-deoxyglucose-positron emission tomography results in all patients. Overall response rate after HD-PAM was 78% and it did not differ among PR or stable/progressive disease patients (P=1.00). Response was associated with better OS: hazard ratio=0.32 (95% confidence interval: 0.13-0.77, P=0.01) irrespective of disease status before HD-PAM. Thirty-three patients (80%) were able to complete the planned treatment, intended as tandem autologous or auto-allo transplant. Hematological and extrahematological toxicity of HD-PAM was manageable, without any treatment-related death. In conclusion, HD-PAM is a valuable therapeutic option in relapsed/refractory HL patients with active disease after salvage therapy, with an impressive 78% overall response rate and 80% rate of proceeding to further transplantation. The present data may be integrated with the growing literature on new drugs in the field of relapsed/refractory HL.

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Autografts; Disease-Free Survival; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Recurrence; Stem Cell Transplantation; Survival Rate

There are limited data to guide the choice of high-dose therapy (HDT) regimen before autologous hematopoietic cell transplantation (AHCT) for patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL). We studied 4917 patients (NHL, n = 3905; HL, n = 1012) who underwent AHCT from 1995 to 2008 using the most common HDT platforms: carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) (n = 1730); cyclophosphamide, BCNU, and etoposide (CBV) (n = 1853); busulfan and cyclophosphamide (BuCy) (n = 789); and total body irradiation (TBI)-containing treatment (n = 545). CBV was divided into CBV(high) and CBV(low) based on BCNU dose. We analyzed the impact of regimen on development of idiopathic pulmonary syndrome (IPS), transplantation-related mortality (TRM), and progression-free and overall survival. The 1-year incidence of IPS was 3% to 6% and was highest in recipients of CBV(high) (hazard ratio [HR], 1.9) and TBI (HR, 2.0) compared with BEAM. One-year TRM was 4% to 8%, respectively, and was similar between regimens. Among patients with NHL, there was a significant interaction between histology, HDT regimen, and outcome. Compared with BEAM, CBV(low) (HR, .63) was associated with lower mortality in follicular lymphoma (P < .001), and CBV(high) (HR, 1.44) was associated with higher mortality in diffuse large B cell lymphoma (P = .001). For patients with HL, CBV(high) (HR, 1.54), CBV(low) (HR, 1.53), BuCy (HR, 1.77), and TBI (HR, 3.39) were associated with higher mortality compared with BEAM (P < .001). The impact of specific AHCT regimen on post-transplantation survival is different depending on histology; therefore, further studies are required to define the best regimen for specific diseases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Busulfan; Carmustine; Cyclophosphamide; Cytarabine; Drug Administration Schedule; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Myeloablative Agonists; Registries; Retrospective Studies; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Whole-Body Irradiation

Optimal conditioning remains a challenge in lymphomas. We designed a regimen consisting of Busulfex, etoposide and melphalan (BuEM). We retrospectively analyzed the outcome of patients conditioned with carmustine, etoposide, cytarabine and melphalan (BEAM) or BuEM in matched-pair analysis on a planned 2:1 ratio. Eighty-seven patients treated with BEAM who fulfilled the matching criteria were randomly selected. Two-year progression-free survival/overall survival (PFS/OS) were 63.2%/76.7% for BEAM vs. 65.6%/79.8% for BuEM after 64.7 and 42.7 months, respectively. Furthermore, marginally better PFS and OS were noted in Hodgkin lymphoma (HL) after BuEM. In multivariate analysis, PFS was superior in HL, chemosensitive disease and complete remission post-transplant. BEAM correlated with faster engraftment, reduced infections, less mucositis and liver toxicity, and BuEM with less need for blood cell and platelet transfusions and granulocyte colony-stimulating factor administration. In conclusion, BuEM was well tolerated and equally highly efficacious as BEAM for non-Hodgkin lymphoma and offered marginally significantly improved PFS and OS in HL with acceptable toxicity and zero mortality.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carmustine; Cytarabine; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Matched-Pair Analysis; Melphalan; Middle Aged; Neoplasm Staging; Podophyllotoxin; Retrospective Studies; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

Intensive chemotherapy followed by autologous stem cell transplantation is the treatment of choice for patients with hematological malignancies. The objective of the present study was to evaluate the outcomes of patients with mainly lymphoma and multiple myeloma after autologous stem cell transplant. The pretransplant workup consisted of the complete blood count, an evaluation of the liver, kidney, lung, and infectious profile, chest radiographs, and a dental review. For lymphoma, all patients who achieved at least a 25% reduction in the disease after salvage therapy were included in the study. Mobilization was done with cyclophosphamide, followed by granulocyte colony-stimulating factor, 300 µg twice daily. The conditioning regimens included BEAM (carmustine, etoposide, cytarabine, melphalan) and high-dose melphalan. A total of 206 transplants were performed from April 2004 to December 2014. Of these, 137 were allogeneic transplants and 69 were autologous. Of the patients receiving an autologous transplant, 49 were male and 20 were female. Of the 69 patients, 26 underwent transplantation for Hodgkin's lymphoma, 23 for non-Hodgkin's lymphoma, and 15 for multiple myeloma and 4 and 1 for Ewing's sarcoma and neuroblastoma, respectively. The median age ± SD was 34 ± 13.1 years (range, 4-64). A mean of 4.7 × 10⁸ ± 1.7 mononuclear cells per kilogram were infused. The median time to white blood cell recovery was 18.2 ± 5.34 days. Transplant-related mortality occurred in 10 patients. After a median follow-up period of 104 months, the overall survival rate was 86%. High-dose chemotherapy, followed by autologous stem cell transplant, is an effective treatment option for patients with hematological malignancies, allowing further consolidation of response.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multiple Myeloma; Transplantation Conditioning; Transplantation, Autologous

High-dose chemotherapy followed by autologous hematopoietic cell transplantation (HCT) improves outcomes in relapsed lymphoma, but the relative efficacy of different preparative regimens is not well defined. We included patients undergoing autologous HCT using BEAM (carmustine, 300 mg/m(2), etoposide, cytarabine, and melphalan) or BEP (carmustine 600 mg/m(2), etoposide, and cisplatin) between January 2004 and December 2013; 65 patients received BEP and 64 patients BEAM. Both cohorts were similar for advanced-stage disease, extranodal and bulky disease, and prior therapies. Median neutrophil and platelet engraftment was 10 and 20 days for both regimens, respectively. Febrile neutropenia, serum creatinine concentration increase, and electrolyte abnormalities were more frequent with BEP. Incidence of carmustine pneumonitis was not higher with BEP, likely the result of corticosteroid prophylaxis, although 2 cases of fatal pneumonitis were observed after BEP. One-year nonrelapse mortality was 6.8% after BEP and 0% after BEAM (P = .379). After a median follow-up of 39.4 months (range, 1 to 128), 4-year rates of overall survival (OS) after BEP and BEAM were 80.4% and 72.3%, respectively (P = .611). Diffuse large B cell lymphoma patients transplanted after early relapse post-rituximab-based first-line therapy presented 3-year rates of OS and progression-free survival (PFS) of 73.8% and 65%, respectively. There were no statistically significant differences in the OS and PFS of follicular lymphoma, mantle cell lymphoma, or Hodgkin lymphoma. BEP is a valid alternative to BEAM in autologous HCT. Although associated with more renal and electrolytic toxicities, BEP results in similar disease control and long-term survival as BEAM. Prospective studies are needed to confirm whether intensification of conditioning regimens for autologous HCT can improve disease control in high-risk relapsed lymphoma patients.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Cytarabine; Etoposide; Female; Graft Survival; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Recurrence; Retrospective Studies; Risk; Rituximab; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous

Relationships between pharmacokinetic (PK) parameters of etoposide and toxicity survivals were reported in cancer patients treated at standard doses. The clinical impact of PK variations of etoposide high doses has never been explored in lymphoma patients.. The primary objective of LYMPK study was to prospectively assess the impact of etoposide PK parameters on outcomes in lymphoma patients receiving high-dose chemotherapy regimen (carmustine, cytarabine, etoposide and melphalan) followed by autologous stem cell transplant (ASCT). Individual etoposide PK parameters were estimated with a previously reported bi-compartment model using NONMEM(®) program. The impact of PK parameters on toxicity and survival was assessed using univariate/multivariate analyses.. A total of 91 patients with malignant lymphoma [non-Hodgkin's lymphoma (NHL): 79; Hodgkin's lymphoma: 12] at first line (n = 49) or relapse (n = 42) were enrolled in five centers. Large inter-individual variabilities in individual PK values were found for the same administration doses. In NHL patients, cumulative higher trough concentrations over the eight administrations of the first cycle (TotC min, categorized by the median 58.71 mg/L) had significant prognostic value regarding the 5-year progression-free survival (PFS: 73.6 vs 46.5 %, P = 0.015) and 5-year overall survival (OS: 74.0 vs 52.2 %, P = 0.034). Using a Cox model analysis, integrating disease settings (first line vs recurrent disease), simplified IPI and other prognostic factors, TotC min was the only significant independent prognostic factor influencing PFS, disease-specific survival and OS.. This prospective study suggests survival of NHL patients treated with BEAM regimen and ASCT might be improved by increasing etoposide administration dose, or plasma concentration-based adjustment.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bilirubin; Carmustine; Creatinine; Cytarabine; Disease-Free Survival; Etoposide; Female; Hodgkin Disease; Humans; Kaplan-Meier Estimate; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Serum Albumin; Transplantation, Autologous; Treatment Outcome; Young Adult

High-dose therapy with autologous stem cell transplant (autoSCT) is standard therapy for relapsed/refractory Hodgkin lymphoma, although the optimal conditioning regimen remains uncertain. We conducted a retrospective analysis of 100 consecutive patients with relapsed/refractory Hodgkin lymphoma who underwent autoSCT between 1998 and 2009. There were 60 patients who received busulfan, melphalan and thiotepa (BuMelTt) conditioning and 40 who received other common regimens. There were no significant differences in patient characteristics between the two groups. With a median follow-up of 4.3 years, the 5-year overall survival (OS) was superior for patients who received BuMelTt versus other conditioning (73% vs. 44%, p = 0.05). BuMelTt was also associated with an improved 5-year progression-free survival (66% vs. 37%, p = 0.03). There were no differences in length of hospitalization, febrile neutropenia, hepatic veno-occlusive disease or 100-day non-relapse mortality (NRM). There were more cases of severe mucositis but fewer episodes of bacteremia with BuMelTt. Our results suggest that BuMelTt may be a superior conditioning regimen for autoSCT in Hodgkin lymphoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Neoplasm Staging; Prognosis; Thiotepa; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

Abstract Allogeneic transplant using reduced intensity conditioning is a therapeutic option for patients with Hodgkin lymphoma (HL) who relapse after an autograft. This was a prospective study of 31 consecutive eligible patients with HL who relapsed after an autograft and underwent an allograft using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning. At a median follow-up of 7 years the progression-free survival (PFS) was 36% (95% confidence interval [CI] 19-54%) and overall survival (OS) was 42% (95% CI 23-59%). In multivariate analysis only residual disease at the time of transplant predicted outcome, with a 4-year PFS and OS of 62% and 75% for patients with minimal residual disease versus 8% and 8% for patients with gross residual disease, respectively (p = 0.005 and p = 0.001, respectively). This benefit seemed to be irrespective of chemosensitivity, with an OS for patients with chemorefractory yet minimal disease of 71% at 4 years. BEAM allogeneic transplant is effective in producing long-term remissions after autograft failure. Regardless of chemosensitivity, minimizing tumor burden pre-transplant may improve long-term outcome.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Disease Progression; Etoposide; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Neoplasm Recurrence, Local; Neoplasm, Residual; Prognosis; Transplantation, Autologous; Transplantation, Homologous; Treatment Failure; Treatment Outcome

The purpose of this national retrospective study was to evaluate the outcome in children with relapsed or primary refractory Hodgkin lymphoma [HL] after a primary chemotherapy alone treatment strategy. Between 2000 and 2005, 80 children with relapsed [n = 69] or primary refractory [n = 11] HL were treated on a standardized treatment protocol of 4-6 cycles of EPIC [etoposide, prednisolone, ifosfamide and cisplatin] chemotherapy. Radiotherapy was recommended to all relapsed sites. High dose therapy with stem cell rescue [SCT] was recommended for patients with poor response. The 5-year overall survival [OS] and progression-free survival from relapse was 75·8% [64·8-83·9] and 59·9% [48·3-69·7] respectively. Duration of first remission was strongly associated with OS; risk of death was decreased by 53% [Hazard ratio (HR): 0·47, 95% confidence interval (CI): 0·19-1·18] for those with a time from end of treatment to relapse of 3-12 months (compared to <3 months) and reduced by 80% (HR 0·20, 95% CI: 0·04-0·90) for those >12 months after end of treatment. Other poor prognostic factors included advanced stage disease at relapse and B symptoms at first diagnosis. The most important factor associated with salvage failure was time to relapse. Survival outcome in children with primary refractory HL is poor.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Child; Chlorambucil; Cisplatin; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Dexamethasone; Disease-Free Survival; Doxorubicin; Epirubicin; Etoposide; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Ifosfamide; Kaplan-Meier Estimate; Melphalan; Multicenter Studies as Topic; Neoplasm Staging; Prednisolone; Prednisone; Procarbazine; Prognosis; Radiotherapy, Adjuvant; Recurrence; Remission Induction; Retrospective Studies; Salvage Therapy; Treatment Outcome; Vinblastine; Vincristine

The management of relapsed or refractory Hodgkin's lymphoma (RR-HL) remains a challenge for hematologists and oncologists. Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for RR-HL. However, one of the most controversial aspects is which the best salvage protocol could be. We retrospectively analyzed 82 consecutive RR-HL who received etoposide, steroids, ara-C, and cisplatin (ESHAP) as salvage therapy followed by ASCT. Fifty percent of patients were refractory and 23 % early relapses. Overall response rate (ORR) was 67 % (50 % complete remission (CR)). Ninety one percent of patients (75/82) were transplanted. With a mean follow-up of 87 ± 53 months, the median progression-free survival (PFS) and time to tumor progression (TTP) for the whole population were 52 and 56 months, respectively, and the 5-year overall survival was 72.6 %. Achieving CR after ESHAP was associated with a longer PFS (78 vs 16 % 5-year PFS, respectively, P < 0.01) and TTP (80 vs 19 % 5-year TTP, respectively, P < 0.01). However, there were no differences for overall survival (OS) when comparing CR and partial response (PR) after ESHAP. Toxicity was low and <10 % of patients developed neutropenic fever, with no toxic deaths. Mobilization was possible in 94 % of patients. ESHAP is a safe and efficient therapeutic option for patients with RR-HL who are candidates for ASCT, since it combines a high response rate and mobilizing potential with a low toxicity profile.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Cisplatin; Combined Modality Therapy; Cytarabine; Drug Evaluation; Etoposide; Febrile Neutropenia; Female; Follow-Up Studies; Hematopoietic Stem Cell Mobilization; Hodgkin Disease; Humans; Kaplan-Meier Estimate; Male; Melphalan; Methylprednisolone; Middle Aged; Radionuclide Imaging; Retrospective Studies; Salvage Therapy; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome; Young Adult

Modern treatment of Hodgkin's lymphoma (HL) has transformed its prognosis but causes late effects, including premature menopause. Cohort studies of premature menopause risks after treatment have been relatively small, and knowledge about these risks is limited.. Nonsurgical menopause risk was analyzed in 2127 women treated for HL in England and Wales at ages younger than 36 years from 1960 through 2004 and followed to 2003 through 2012. Risks were estimated using Cox regression, modified Poisson regression, and competing risks. All statistical tests were two-sided.. During follow-up, 605 patients underwent nonsurgical menopause before age 40 years. Risk of premature menopause increased more than 20-fold after ovarian radiotherapy, alkylating chemotherapy other than dacarbazine, or BEAM (bis-chloroethylnitrosourea [BCNU], etoposide, cytarabine, melphalan) chemotherapy for stem cell transplantation, but was not statistically significantly raised after adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). Menopause generally occurred sooner after ovarian radiotherapy (62.5% within five years of ≥5 Gy treatment) and BEAM (50.9% within five years) than after alkylating chemotherapy (24.2% within five years of ≥6 cycles), and after treatment at older than at younger ages. Cumulative risk of menopause by age 40 years was 81.3% after greater than or equal to 5Gy ovarian radiotherapy, 75.3% after BEAM, 49.1% after greater than or equal to 6 cycles alkylating chemotherapy, 1.4% after ABVD, and 3.0% after solely supradiaphragmatic radiotherapy. Tables of individualized risk information for patients by future period, treatment type, dose and age are provided.. Patients treated with HL need to plan intended pregnancies using personalized information on their risk of menopause by different future time points.

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Child; Child, Preschool; Cytarabine; Dacarbazine; Doxorubicin; England; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Infant; Melphalan; Menopause, Premature; Ovary; Poisson Distribution; Proportional Hazards Models; Radiotherapy Dosage; Risk Assessment; Surveys and Questionnaires; Vinblastine; Wales; Young Adult

Despite the well-defined role of autologous haematopoietic stem cell transplantation (autoHCT) in the treatment of patients with relapsed or refractory Hodgkin lymphoma (HL), relapse remains the main cause of transplant failure. We retrospectively evaluated long-term outcome and prognostic factors affecting survival of 132 patients with refractory (n = 89) or relapsed HL (n = 43) treated with autoHCT following modified BEAM. With a median follow-up of 68 months, the 10-year overall survival (OS) and progression-free survival (PFS) were 76 and 66 %, respectively. The 10-year cumulative incidence of second malignancies was 7 %. In multivariate analysis, age ≥45 years, more than one salvage regimens and disease status at transplant worse than CR were factors predictive for poor OS. In relapsed HL, age at transplant, response duration (<12 vs. ≥12 months) and the number of salvage regimens were independent predictors for PFS. In the refractory setting, disease status at autoHCT and the number of salvage regimens impacted PFS. The number of risk factors was inversely correlated with PFS in both relapsed and refractory HL (p = 0.003 and <0.001, respectively). The median PFS for patients with >1 risk factor in the relapsed and refractory setting was 5 and 11 months, respectively, in comparison with the median PFS not reached for patients with 0-1 risk factor in both settings. We conclude that high proportion of patients with relapsed/refractory HL can be cured with autoHCT. However, the presence of two or more risk factors helps to identify poor prognosis patients who may benefit from novel treatment strategies.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Disease-Free Survival; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Risk Factors; Transplantation, Autologous; Young Adult

Autologous stem cell transplantation is the standard of care for patients with relapsed HL and the long-term outcomes for survivors 2 years after ASCT have not been well described. No prospective trials have compared the effect of different conditioning regimens on outcomes.. We searched the Nebraska Lymphoma Study Group database to identify patients with HL who received ASCT from 1984 to 2007. Patients were conditioned with either CBV (cyclophosphamide, carmustine, and etoposide) or BEAM (carmustine, etoposide, cytarabine, and melphalan).. At a median follow-up of 8 (range, 2-26) years, 225 patients were alive and disease-free 2 years after ASCT. Analysis was limited to these patients. At 5 years, the progression-free survival (PFS) was 92% for BEAM and 73% for CBV (P = .002) and the overall survival (OS) was 95% for BEAM and 87% for CBV (P = .07). At 10 years, the PFS was 79% for BEAM and 59% for CBV (P = .01) and the OS was 84% for BEAM and 66% for CBV (P = .02).. Patients with HL who are disease-free and alive 2 years after ASCT have favorable outcomes. We observed lower risk of progression and longer survival associated with use of BEAM vs. CBV. Patients in the BEAM group received a transplant in more recent years so we cannot exclude the possibility that the superior outcomes seen in the BEAM group are because of better supportive care, use of peripheral blood stem cell grafts, or improvements in salvage therapies before transplantation.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Cyclophosphamide; Cytarabine; Disease-Free Survival; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Prognosis; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of Stanford clinical trials.. Patients with HL treated at Stanford with at least 5 years of follow-up after completing therapy were identified from our database. Records were reviewed for outcome and development of t-AML/MDS.. Seven hundred fifty-four patients treated from 1974 to 2003 were identified. Therapy varied across studies. Radiotherapy evolved from extended fields (S and C studies) to involved fields (G studies). Primary chemotherapy was mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in S studies; MOPP, PAVe, vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in C studies; and VbM (reduced dose of bleomycin compared with VBM) or mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) in G studies. Cumulative exposure to alkylating agent (AA) was notably lower in the G studies compared with the S and C studies, with a 75% to 83% lower dose of nitrogen mustard in addition to omission of procarbazine and melphalan. Twenty-four (3.2%) of 754 patients developed t-AML/MDS, 15 after primary chemotherapy and nine after salvage chemotherapy for relapsed HL. The incidence of t-AML/MDS was significantly lower in the G studies (0.3%) compared with the S (5.7%) or C (5.2%) studies (P < .001). Additionally, in the G studies, no t-AML/MDS was noted after primary therapy, and the only patient who developed t-AML/MDS did so after second-line therapy.. Our data demonstrate the relationship between the cumulative AA dose and t-AML/MDS. Limiting the dose of AA and decreased need for secondary treatments have significantly reduced the incidence of t-AML/MDS, which was extremely rare in the G studies (Stanford V era).

Topics: Academic Medical Centers; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; California; Chemotherapy, Adjuvant; Clinical Trials as Topic; Dacarbazine; Databases, Factual; Doxorubicin; Drug Administration Schedule; Female; Hodgkin Disease; Humans; Incidence; Leukemia, Myeloid, Acute; Male; Mechlorethamine; Melphalan; Methotrexate; Myelodysplastic Syndromes; Neoplasm Staging; Neoplasms, Second Primary; Prednisone; Procarbazine; Radiotherapy Dosage; Radiotherapy, Adjuvant; Retrospective Studies; Risk; Vinblastine; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Busulfan; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Melphalan; Risk Factors; Thiotepa; Transplantation, Autologous; Treatment Outcome

Hodgkin lymphoma (HL) is cured in the majority of children and adolescents. However, there remains a group of patients with primary refractory or relapsed disease for whom cure is more difficult to achieve. Most of these patients receive high-dose chemotherapy followed by auto-SCT, with expected cure rates ranging from 40 to 60%. Conditioning regimens often consist of multiple non-cross-resistant agents, with well-described risks of morbidity and mortality. The use of single-agent high-dose melphalan (HDM) as conditioning, before autologous rescue, has been described in adult patients at our center, with comparable efficacy and less morbidity. We present a series of eight pediatric patients conditioned with single-agent HDM before autologous stem cell rescue for relapsed and primary refractory HL. All patients engrafted with a median of 12 days to neutrophil engraftment. Two patients subsequently relapsed. Seven patients are currently alive, and seven of eight patients have no evidence of disease (one in CR3). Toxicities included grade 4 hematologic in 8/8, grade 3 mucositis in 3/8, grade 3 infectious in 2/8 and grade 4 infectious in 1/8. Our analysis suggests that this regimen is feasible in pediatric patients with acceptable engraftment and toxicity.

Topics: Adolescent; Canada; Child; Drug Resistance, Neoplasm; Female; Hodgkin Disease; Humans; Lymphoma; Male; Melphalan; Myeloablative Agonists; Recurrence; Retrospective Studies; Stem Cell Transplantation; Transplantation Conditioning

The purpose of the present study was to review retrospectively our results of double high-dose therapy with DICEP (dose-intensified cyclophosphamide 5.25 g/m(2), etoposide 1.05 g/m(2), and cisplatin 105 mg/m(2)) re-induction followed by high dose melphalan 200 mg/m(2) (HDM) and autologous stem cell transplantation (ASCT) for 73 consecutive patients with relapsed (n = 43) or refractory (n = 30) classical Hodgkin lymphoma (HL) treated between June 1995 and November 2009. DICEP chemotherapy resulted in successful stem cell mobilization in 71 patients (97%), with a median CD34 (+) cell collection of 15.6 × 10(6)/kg. With a median follow-up of 56 months post-DICEP, the 5-year progression free survival (PFS) and overall survival (OS) rates were 61% [95%CI = 49-72%] and 80% [95%CI = 69-89%], respectively. The 5-year PFS was 65% vs. 30% for DICEP responders vs. nonresponders (logrank p = 0.003) and 89% for International Prognostic Score (IPS) = 0-1, 56% for IPS = 2-3, and 24% for IPS = 4-7 (logrank p < 0.001). Response to DICEP and IPS at relapse were the only two factors that independently predicted PFS and OS in multivariate analyses. Treatment-related mortality was 1%. In conclusion, DICEP-HDM/ASCT is well tolerated double high-dose therapy associated with excellent stem cell mobilization and favorable PFS and OS outcomes for relapsed as well as primary refractory HL.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Etoposide; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Multivariate Analysis; Recurrence; Retrospective Studies; Salvage Therapy; Transplantation, Autologous; Treatment Outcome; Young Adult

The management of patients with relapsed or refractory Hodgkin's lymphoma who achieve less than a partial response to first-line salvage chemotherapy is unclear. The objective of this study was to evaluate response and outcomes to second-line salvage and autologous stem cell transplantation in patients not achieving a complete or partial response to platinum-containing first-line salvage chemotherapy.. Consecutively referred transplant-eligible patients with relapsed/refractory Hodgkin's lymphoma after primary chemotherapy received gemcitabine, dexamethasone, and cisplatin as first salvage chemotherapy. Those achieving a complete or partial response, and those with a negative gallium scan and stable disease with bulk <5 cm proceeded to high-dose chemotherapy and autologous stem cell transplantation. Patients with progressive disease or stable disease with a positive gallium scan or bulk ≥ 5 cm were given second salvage chemotherapy with mini-BEAM (carmustine, etoposide, cytarabine, melphalan). Patients who responded (according to the same definition) proceeded to autologous stem cell transplantation.. One hundred and thirty-one patients with relapsed/refractory Hodgkin's lymphoma received first-line salvage gemcitabine, dexamethasone, and cisplatin; of these patients 99 had at least a partial response (overall response rate 76%). One hundred and twelve (85.5%) patients proceeded to autologous stem cell transplantation, while the remaining 19 (14.5%) patients received mini-BEAM. Among these 19 patients, six had at least a partial response (overall response rate 32%), and nine proceeded to autologous stem cell transplantation. The remaining ten patients received palliative care. Seven of the nine patients transplanted after mini-BEAM had a subsequent relapse. Patients receiving second salvage mini-BEAM had poor outcomes, with a 5-year progression-free survival rate of 11% and a 5-year overall survival rate of 20%.. Patients who require a second salvage regimen to achieve disease control prior to autologous stem cell transplantation have a relatively poor outcome and should be considered for alternative treatment strategies.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Drug Resistance, Neoplasm; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Prospective Studies; Remission Induction; Retrospective Studies; Salvage Therapy; Survival Rate; Transplantation, Autologous; Young Adult

Topics: Adult; Busulfan; Drug Administration Schedule; Female; Fibroblast Growth Factor 7; Gastric Mucosa; Hodgkin Disease; Humans; Intestinal Mucosa; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mucositis; Retrospective Studies; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Carmustine; Cytarabine; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Platelet Count; Podophyllotoxin; Polyethylene Glycols; Recombinant Proteins; Recovery of Function; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous

Patients with relapsed or refractory lymphoma can be cured with stem cell transplantation if they are shown to have disease that is responsive to salvage chemotherapy. Patients who fail to respond to first-line salvage chemotherapy tend to do very poorly. Here we report on 39 such patients who received mini-BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy as second or subsequent-line salvage chemotherapy. Fifty-six percent of these patients had primary refractory disease and a further 28% had responses to first-line therapy that lasted <12 months. Seventy-two percent had progressive disease following the salvage chemotherapy administered immediately prior to mini-BEAM and the remaining 28% had stable disease. Overall there was a 38% response to mini-BEAM (complete response = 28%, partial response = 10%). Patients with Hodgkin lymphoma (HL) had a higher response rate compared to those with diffuse large B cell lymphoma (DLBCL) (63% vs. 20%). Seventy-four percent of HL patients were able to proceed to transplantation compared with 30% of patients with DLBCL. Mini-BEAM is a very effective bridge to transplantation in very poor risk patients with HL who have failed to respond to first-line salvage chemotherapy. Its efficacy in non-Hodgkin lymphoma is more modest.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Middle Aged; Recurrence; Salvage Therapy; Survival Analysis; Transplantation Conditioning; Treatment Outcome; Young Adult

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Biofilms; Bleomycin; Carmustine; Catheter-Related Infections; Central Venous Catheters; Cisplatin; Cross Infection; Cytarabine; Dacarbazine; Deoxycytidine; Doxorubicin; Drug Resistance, Multiple, Bacterial; Equipment Contamination; Etoposide; Female; Gemcitabine; Gram-Negative Bacterial Infections; Hodgkin Disease; Humans; Immunocompromised Host; Melphalan; Methylobacterium; Prednisone; Ribotyping; Spain; Vinblastine

Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Etoposide; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lomustine; Lymphoma, Non-Hodgkin; Melphalan

Stomatitis, including oral mucositis and ulcerations induced by HSV-reactivation are major sources of morbidity after high-dose (HD) chemotherapy and subsequent autologous hematopoietic stem cell transplantation (SCT). While increased synthesis of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α)-as well as reactivation of viral infections have frequently been observed in this setting, data on their association with the severity of mucositis is limited.. Fifteen patients with Hodgkin's or non-Hodgkin's lymphoma receiving HD conditioning chemotherapy and autologous SCT were assessed with respect to oral pain and severity of stomatitis on day -6, 0, +5 to +7, +13 to +15, and +100. On the same dates, IL-1 and TNF-α were quantified in saliva and screening for a wide range of viral pathogens was carried out by cell culture and PCR and complemented by serological analyses. t Tests were used to assess potential associations between these variables.. All but one patient had a positive HSV IgG titer at baseline. Reactivation as confirmed by HSV PCR was observed in seven patients (50%). There was a significant association between the presence of HSV in saliva samples and severity of stomatitis (t test, p = 0.015). The highest concentration of TNF-α and IL-1 coincided with the maximum intensity of stomatitis, but the association was not significant.. We found a significant association between the presence of HSV in saliva samples and severity of stomatitis in patients receiving HD chemotherapy and subsequent autologous SCT. While acyclovir prophylaxis has become standard for patients undergoing allogeneic SCT, this issue has not been sufficiently explored for other chemotherapy regimens. Based on our findings, conduction of a well-powered controlled randomized trial may be warranted.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Cytokines; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Hodgkin Disease; Humans; Inflammation; Interleukin-1; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Saliva; Severity of Illness Index; Statistics as Topic; Stem Cell Transplantation; Stomatitis; Transplantation, Autologous; Tumor Necrosis Factor-alpha; Young Adult

Hodgkin lymphoma (HL) can be aggressive and intractable in some cases. Patients who relapse after autologous HCT (auto-HCT) have limited treatment options. City of Hope reports our experience in the use of reduced intensity allogeneic hematopoietic cell transplantation (allo-HCT) in 24 heavily pretreated patients with relapsed HL, between January 2003 and December 2008. The median number of prior therapies was 5; 20/24 patients had prior auto-HCT. The conditioning regimen for all patients was fludarabine and melphalan. With a median follow-up for living patients of 39.0 months, at 2 years the overall survival (OS) was 60% (95% CI 42, 72) and the progression-free survival was 27% (95% CI 22, 32). Non-relapse mortality was 13.1% (95% CI 5.1, 31.4) at 2 years. The incidence of grade II-IV aGVHD was 45.8% and 8.3% for grade III-IV. Allo-HCT in heavily pretreated relapsed Hodgkin lymphoma is feasible, tolerable, and can induce durable clinical remissions.

Topics: Adolescent; Adult; Antineoplastic Agents; Clinical Trials as Topic; Disease Progression; Disease-Free Survival; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Recurrence; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine; Young Adult

Our purpose was to assess efficacy and toxicity of high-dose chemotherapy (HDCT) and ASCT in patients with relapsed and refractory Hodgkin's lymphoma (HL) aged 60 years and older and compare the results with a group of younger HL patients treated in a similar manner. We identified 15 consecutive patients, with HL aged 60 years and older who underwent HDCT (etoposide 60 mg/kg+ melphalan 160 mg/m(2)) and ASCT at our institution from May 2001 to March 2008. The results were compared with a cohort of 157 younger HL patients treated in a similar manner from January 1999 to December 2006. After a median follow-up of 2.5 years, PFS at 3 years after ASCT was 73% (95% confidence interval (CI) 37-90) for the older group and 56% (95% CI 46-64) for the younger group (P=0.45); OS after ASCT was 88% (95% CI 39-98) for the older group and 84% (95% CI 75-90) for the younger group (P=0.80). No transplant-related deaths were seen. Our study suggests that ASCT is feasible for selected elderly patients with HL, giving similar results to younger patients in terms of survival and toxicity.

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Etoposide; Female; Hematopoietic Stem Cell Mobilization; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Salvage Therapy; Stem Cell Transplantation; Survival Analysis; Transplantation, Autologous; Young Adult

Pulmonary Langerhans histiocytosis (PLH) is a rare disease due to the accumulation of Langerhans cells at the level of the bronchioles. These dendritic immunocytes form granulomata and destroy the wall of the airway. We report a case of PLH developing at the same time as Hodgkin's lymphoma in a young woman who smoked tobacco and cannabis. We observed a complete remission of the PLH lesions parallel to the remission of the Hodgkin's lymphoma after chemotherapy, in the absence of any change in the consumption of tobacco and cannabis. This observation leads us to discuss the potential relationships between PLH on one hand, and smoking, the lymphoma and its treatment on the other.

Topics: Accidents, Traffic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bronchioles; Carmustine; Cytarabine; Dacarbazine; Doxorubicin; Etoposide; Female; Histiocytosis, Langerhans-Cell; Hodgkin Disease; Humans; Ifosfamide; Incidental Findings; Lung Diseases; Lymphatic Diseases; Marijuana Smoking; Melphalan; Methylprednisolone; Mitoguazone; Remission Induction; Smoking; Tomography, X-Ray Computed; Vinblastine; Vindesine; Vinorelbine; Young Adult

Few diseases have a prognosis worse than Hodgkin's lymphoma (HL), patients relapsing after autologous or allogeneic stem cell transplantation. Here, we report two highly refractory patients with HL who successfully responded to a combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex). Despite the use of a very large number of different drugs (>5 different schemes) including high-dose therapy and autologous and allogeneic stem cell transplantation, both patients proved to be suffering from a highly resistant disease. Fortunately, they finally responded to the ThaCyDex combination, achieving sustained complete remission that would support the running of a trial within this setting.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Deoxycytidine; Dexamethasone; Doxorubicin; Drug Resistance, Neoplasm; Etoposide; Hodgkin Disease; Humans; Male; Mechlorethamine; Melphalan; Organoplatinum Compounds; Paclitaxel; Peripheral Blood Stem Cell Transplantation; Prednisolone; Prednisone; Procarbazine; Remission Induction; Rituximab; Salvage Therapy; Thalidomide; Topotecan; Transplantation, Autologous; Vidarabine; Vinblastine; Vincristine

To evaluate the impact of pegfilgrastim on engraftment, hospital stay and resources in patients with Hodgkin's and non-Hodgkin's lymphoma after conditioning with high-dose BEAM followed by autologous peripheral blood stem cell transplantation (APBSCT) compared with filgrastim.. We reviewed patient charts and our prospective transplantation database for clinical data from the post-transplant period. An integrated cost analysis, including the use of blood products and length of hospital stay, was also performed.. Fourteen (26%) patients with Hodgkin's lymphoma and 40 (74%) patients with non-Hodgkin's lymphoma were analyzed. Thirty-four (68%) patients received single-dose pegfilgrastim (6 mg), and 20 (32%) patients received daily filgrastim (5 μg/kg) after APBSCT. No differences were observed regarding duration of neutropenia grade 4 (pegfilgrastim median 7 days/filgrastim median 8 days; p = 0.13), thrombocytopenia grade 4 (7/9.5 days, respectively; p = 0.21), fever (4.5/2 days; p = 0.057), intravenous antibiotic treatment (11/10 days; p = 0.75) or length of hospital stay (16.5/16 days; p = 0.27) between the groups. The use of pegfilgrastim resulted in 12% higher treatment-related costs when compared to filgrastim, without reaching statistical significance (p = 0.38).. Pegfilgrastim appears to be equivalent to filgrastim after high-dose BEAM followed by APBSCT in the treatment of lymphoma patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Drug Administration Schedule; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Length of Stay; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neutropenia; Peripheral Blood Stem Cell Transplantation; Podophyllotoxin; Polyethylene Glycols; Recombinant Proteins; Severity of Illness Index; Thrombocytopenia; Time Factors; Transplantation, Autologous; Treatment Outcome; Young Adult

This study was done to evaluate the frequency and severity of mucositis in the early period of stem cell transplantation (SCT) and the relation of conditioning regimens with mucositis.. Patients with hematologic or solid tumors who underwent conditioning regimen were asked to score mucositis severity daily from the first day to the tenth day of reinfusion. Patient-reported scoring was performed according to a five-grade scale (0: no symptom; 1: mild; 2: moderate; 3: severe; 4: very severe). Total mucositis score (TMS) was defined as the addition of daily mucositis scores for 10 days. A total of 68 SCT (58 autologous and 10 allogeneic) patients, 48 men (71%) and 20 women (29%) were included to the study. Median age of patients was 32.5 (range 15-78) years. The most frequent three diagnosis were non-Hodgkin's lymphoma (37%, n = 25), Hodgkin's lymphoma (12%, n = 8), and multiple myeloma (12%, n = 8). BEAM (n = 27), ICE (n = 17), melphelan 200 mg/m(2) (M200)(n = 8), and TBI+C (total body irradiation + cyclophosphamide) (n = 16) were used as conditioning regimens.. All of the patients experienced mucositis at any grade. TMS in the sixth day was higher than TMS in the first day (p < 0.05). TMS was not related to the diagnosis or gender (p > 0.05). TMS at ICE regimen in the first 5 days after transplantation was more severe than BEAM regimen. TMS at TBI+C regimen was higher than TMS at BEAM regimen from day 4 to day 10 (p < 0.05). The mean percentages of patients who scored severe or very severe mucositis in 10 days was 7.4% in BEAM, 8.9% in ICE, 12.5% in M200, and 31.2% in TBI+C groups.. Patients experience mucositis frequently following conditioning regimen and SCT. The necessity and the timing of prophylaxis for mucositis change due to the type of conditioning regimens.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Neoplasms; Severity of Illness Index; Whole-Body Irradiation; Young Adult

Five years ago (in September, 2003), the activity of the 5th Haemopoietic Stem Cell Transplantation Centre of Hungary has begun. This centre has been registered as No 648. by the European Group for Blood and Marrow Transplantation-Centres.. To supply the needs of stem cell transplantation regions in north-east Hungary and to develop an active co-operation with the Hungarian and international centres.. Transplantations were made according to international criteria.. 150 autologous stem cell transplantations has been performed so far, including 74 patients with myeloma multiplex, 43 patients with non-Hodgkin lymphoma, 27 patients with Hodgkin's disease, 4 patients with autoimmune disease, and one patient with leiomyosarcoma. The survival rates were similar to the previous Hungarian and international data. The centre played a role in other activities using stem cell therapy at the University of Debrecen (dendritic cell vaccine program, stem cell therapy in myocardial infarction, stem cell therapy in peripheral arterial- and autoimmune diseases). This centre performed the largest quantity of the conditioning protocol Zevalin, Bischloronitrosourea, Etoposide, cytosine-Arabinoside, Melphalan in non-Hodgkin lymphoma in Hungary; ten patients were treated with this protocol.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Autoimmune Diseases; Cytarabine; Etoposide; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Hungary; International Cooperation; Kaplan-Meier Estimate; Leiomyosarcoma; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Nitrosourea Compounds; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Dimethylsulfoxide (DMSO) is a solvent commonly used for the cryopreservation of autologous peripheral blood stem cells (APBSC). Side effects upon infusion of DMSO-cryopreserved APBSC mainly consist of nausea, emesis, chills, rigors, and cardiovascular events, such as bradyarrhythmia or hypotension. We report the case of a patient who received DMSO-cryopreserved APBSC after myeloablative chemotherapy for a relapsing lymphoma. The patient developed a rare reaction during the infusion manifesting as transient global amnesia. The clinical course during the reaction is described and an explanation of the possible causes is discussed. This observation underlines the need for an adequate DMSO depletion to limit neurotoxicity or other adverse manifestations.

Topics: Adult; Alkalosis, Respiratory; Amnesia, Retrograde; Amnesia, Transient Global; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Cisplatin; Combined Modality Therapy; Confusion; Cryoprotective Agents; Cytarabine; Dacarbazine; Dexamethasone; Dimethyl Sulfoxide; Doxorubicin; Etoposide; Hippocampus; Hodgkin Disease; Humans; Hyperventilation; Ifosfamide; Magnetic Resonance Imaging; Male; Melphalan; Paresthesia; Peripheral Blood Stem Cell Transplantation; Salvage Therapy; Vinblastine; Vision Disorders

The purpose of this study was to assess prognostic factors and outcome of patients with relapsed/refractory Hodgkin's lymphoma (HL) who received high-dose chemotherapy and autologous stem-cell transplant (ASCT).. Data on 195 patients who received ASCT between 1985 and June 2005 were reviewed. Median time from first treatment to ASCT was 2.6 years (0.4-27.3). Demography at ASCT was 61% stage IV, median age 31 years (18-69), median prior treatment (tx) regimens 3 (2-7), median Hasenclever index 3 (0-6); 150 patients had responding disease [54 complete remission (CR), 96 partial remission (PR)], and 45 patients had untested relapse/refractory disease.. Post-ASCT, 61% (119/195) patients attained CR with an overall response (CR + PR) of 85%. Twelve patients had nonrelapse mortality. Of 119 patients attaining CR, 27 relapsed: 3 after attaining CR for >5 years and 1 after attaining CR for >10 years. Median overall survival (OS)/progression-free survival (PFS) from ASCT was 9 years/2.9 years. Five-year OS/PFS was 55% of 44% and 10-year OS/PFS was 49.4% of 37% for whole group. Twenty (10%) patients developed second cancer (seven secondary acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS)). Probability of developing second cancer at 10 years was 14.7% (95% confidence interval 8.9% to 23.8%) and 24.8% at 19 years.. These data provide the longest follow-up reported for patients receiving ASCT for relapsed/refractory HL. In addition to previously described prognostic factors, our data show that Hasenclever index <3 influences outcome favorably and attaining CR at ASCT leads to a better outcome.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Disease Progression; Disease-Free Survival; Etoposide; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Melphalan; Middle Aged; Multivariate Analysis; Myelodysplastic Syndromes; Recurrence; Remission Induction; Retrospective Studies; Salvage Therapy; Time Factors; Transplantation, Autologous; Treatment Outcome

Topics: Antineoplastic Agents, Alkylating; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Myeloablative Agonists; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neuroblastoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

We designed a prospective study to evaluate the feasibility and efficacy of tandem high-dose chemotherapy (HDCT) in the treatment of refractory or relapsed Hodgkin's lymphoma (HL). Thirty-two patients were treated with salvage chemotherapy (IGEV, ifosfamide, gemcitabine, and vinorelbine) and chemo-sensitive patients received a first HDCT course with melphalan 200 mg/m(2) (MEL200) and a second BEAM course. The median time interval between the two HDCT courses was 66 days. The median number of reinfused CD34(+) cells was 4.7 x 10(6)/kg after MEL200 and 5.8 x 10(6)/kg after BEAM. The hematological reconstitution after both HDCT courses did not differ. No grade III or IV renal, hepatic, lung, cardiac, and neurological toxicity was observed. Severe (grade III and IV) oral mucositis was the most prominent complication affecting 60 and 50% of patients after MEL200 and BEAM, respectively. Fever of unknown origin occurred in 65 and 70% of patients after MEL200 and BEAM, respectively. One patient died from septic shock during the aplasia period following BEAM. In an intention-to-treat analysis, the overall response rate increased after each stage of protocol, ranging from 47% to 65% and 75% after IGEV, MEL200, and BEAM, respectively. Tandem HDCT is feasible and effective in patients with relapsed or refractory HL.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Deoxycytidine; Disease-Free Survival; Etoposide; Female; Gemcitabine; Hodgkin Disease; Humans; Ifosfamide; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Podophyllotoxin; Prospective Studies; Recurrence; Remission Induction; Retrospective Studies; Salvage Therapy; Survival Rate; Transplantation, Autologous; Vinblastine; Vinorelbine

In the present study we report the clinical outcome of 27 patients with refractory or relapsed Hodgkin's lymphoma (HL) undergoing autologous peripheral stem-cell transplantation (ASCT).. On transplant, 18 patients had sensitive disease (SD) and 9 resistant disease (RD). The median time between diagnosis and ASCT was 18 months (range, 7 to 96 months). The conditioning consisted of BEAM regimen.. The 100-day mortality rate was 3%. Three months after transplant, 12 patients transplanted with SD were in complete remission (CR) and only one of the 9 patients transplanted with RD achieved CR. Overall survival and disease-free survival after 3 years were 68% and 60%, respectively.. the present results confirm the efficacy and safety of the ASCT in refractory or relapsed HL patients with SD. Other strategies should be investigated for patients with RD.

Topics: Adolescent; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Cytarabine; Data Interpretation, Statistical; Disease-Free Survival; Drug Resistance, Neoplasm; Etoposide; Follow-Up Studies; Hodgkin Disease; Humans; Melphalan; Neoplasm Staging; Peripheral Blood Stem Cell Transplantation; Recurrence; Remission Induction; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Treatment options for patients who relapse following autologous transplantation for Hodgkin's lymphoma are limited. There are anecdotal reports of lengthy remissions following second autologous procedures, although treatment-related toxicity can be significant. We report a single centre experience of second autologous transplant performed in seven highly selected patients, who relapsed following initial high-dose therapy. They were all young and had slow tempo disease, which was still sensitive to conventional dose chemotherapy. All received BEAM conditioning for the first transplant, and six of the seven received BEAM for the second. All six of these patients regenerated successfully and with no delay, the final patient dying during the procedure following alternative conditioning. Only one case of presumed carmustine-related pneumonitis was seen, which responded rapidly to corticosteroid therapy. Four patients have subsequently relapsed, of whom three have died at 29, 33, and 38 months postprocedure. One is alive with active disease at 68 months, and the final two are alive and in continuing complete remission at 104 and 68 months.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Female; Follow-Up Studies; Graft Survival; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Podophyllotoxin; Prognosis; Recurrence; Remission Induction; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous

We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients with primary refractory Hodgkin's lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%, 92% had ESHAP as salvage. Post-ASCT evaluation showed response in 50 patients (76%); complete response (CR) 37 (56%), partial response 14 (21%), no response or stable disease 3 (5%) and progressive disease in 10 (15%). Another five patients achieved CR after radiation therapy and one after surgery, making total CR 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival (OS) 78 and 57 months, respectively. Event-free survival (EFS) and OS are 36 and 64%, respectively. In all, 47% patients are in CR. Twenty-two patients (33%) died due to disease. Multivariate analysis showed elevated lactate dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Cohort Studies; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Multivariate Analysis; Neoplasm Staging; Podophyllotoxin; Prognosis; Retrospective Studies; Salvage Therapy; Stem Cell Transplantation; Survival Analysis; Treatment Outcome

Cure rates of Hodgkin's disease (HD) with chemotherapy and/or radiotherapy are high. However, a few patients are refractory to treatment or relapse. We describe a patient with mixed cellularity (MC)-type HD with frequent relapses. As all Hodgkin's or Hogan-Reed-Sternberg (HRS) cells expressed CD20, treatment with the anti-CD20 monoclonal antibody rituximab was given.. A 55-year-old man presented with cervical lymphadenopathy. Biopsy revealed HD of MC type in stage IVA (Ann Arbor classification). Complete remission (CR) was achieved after six cycles of doxorubicin-bleomycin-vinblastin-dacarbazine (ABVD) and cyclophosphamid-vincristine-procarbazine-prednison (COPP) regimens. The first relapse occurred 12 months later and was treated with DEXA-BEAM and autologous peripheral blood stem cell transplantation. 7 years later, the patient relapsed again. Histology confirmed the initial diagnosis. Staging revealed a stage IVA. A partial remission was induced with two further DEXA-BEAM cycles (dexamethasone, BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea], ectoposide, ara-C, melphalan). 4 months later, the disease progressed. Despite treatment with gemcitabine there was no response. As all Hogan-Reed-Sternberg (HRS) cells were CD20 positive, rituximab (monoclonal antibodies) was given at a dose of 375 mg/m2 once a week for 4 weeks in an outpatient setting.. Treatment was well tolerated. A complete remission was achieved 2 months later. No infectious episodes occurred. After 30 months, the patient relapsed again. A second treatment with rituximab yielded another complete remission which was maintained for 20 months.. HRS cells are derived from germinal center B-cells in more than 90% of cases, B-cell markers being present in 80% of classical HD. CD20 expressions vary from 21-80%. A few patients with HD treated with rituximab have been reported. Most of these cases had lymphocyte-predominant HD. In our patient the safety and efficacy of rituximab in relapsed CD20-positive classical HD of an MC type was demonstrated to achieve long-lasting remission.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Cyclophosphamide; Cytarabine; Dacarbazine; Dexamethasone; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Lymph Nodes; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Peripheral Blood Stem Cell Transplantation; Prednisone; Procarbazine; Remission Induction; Rituximab; Treatment Outcome; Vinblastine; Vincristine

The objective of this study was to compare the response rates, ability to mobilize autologous hematopoietic (peripheral blood) stem cells (PBSCs), and progression-free survival (PFS) after second-line chemotherapy with either gemcitabine, dexamethasone, and cisplatin (GDP) or carmustine, etoposide, cytarabine, and melphalan (mini-BEAM) followed by high-dose therapy and hematopoietic stem cell transplantation (ASCT) for patients with recurrent or refractory Hodgkin lymphoma.. The outcomes of 68 consecutive patients who were referred for salvage therapy (34 patients received mini-BEAM, and 34 patients received GDP) were compared retrospectively. Patients received mini-BEAM as inpatient treatment every 3-4 weeks, whereas GDP was administered on an outpatient basis every 3 weeks. Responding patients proceeded to stem cell mobilization, followed by high dose etoposide and melphalan, and ASCT. Patients who had disease bulk at recurrence that measured > 5 cm received involved-field radiation post-ASCT.. The response rate to GDP prior to ASCT (complete responses, unconfirmed complete responses, and partial responses) was 62% (95% confidence interval [95% CI], 45-78%) compared with 68% (95% CI, 52-83%) for mini-BEAM (P = 0.61). After mobilizing chemotherapy, the proportion of patients for whom the target PBSC number of > or = 5 x 10(6) CD34-positive cells/kg was obtained was 97% after GDP and 57% after MB (P = 0.0003). More patients completed collection with a single apheresis procedure after GDP than after mini-BEAM (73% vs. 36%; P = 0.004), and fewer patients in the GDP group required bone marrow harvesting to proceed to ASCT. After a median follow-up of 1.8 years after ASCT, PFS was significantly better for patients who received GDP compared with patients who received mini-BEAM (74% vs. 35% at 1.5 yrs, respectively; P = 0.005). Overall survival at 1.5 years was 91% after GDP and 82% after mini-BEAM (P = 0.23).. Although this was a retrospective analysis, response to GDP and early PFS after ASCT compared favorably with mini-BEAM salvage chemotherapy. Based on these data, the authors believe that a Phase III trial comparing GDP with mini-BEAM or other platinum-containing regimens is warranted.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Cytarabine; Deoxycytidine; Dexamethasone; Disease Progression; Disease-Free Survival; Etoposide; Female; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Prognosis; Recurrence; Retrospective Studies; Salvage Therapy; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Drug Administration Schedule; Etoposide; Hodgkin Disease; Humans; Melphalan; Recurrence; Salvage Therapy

Topics: Adult; Androstenes; Angiography; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Contraceptives, Oral, Synthetic; Cytarabine; Etoposide; Female; Hodgkin Disease; Humans; Immunotherapy; International Normalized Ratio; Lynestrenol; Melphalan; Mineralocorticoid Receptor Antagonists; Risk; Risk Factors; Time Factors; Venous Thrombosis; Warfarin

Despite the best available agents to prevent mucositis, most patients receiving high-dose chemoradiotherapy regimens experience severe mucositis, and new therapies are needed. In this study, we evaluated the safety and tolerability of a milk-derived growth factor extract (PV701 mouthwash) intended to prevent oral mucositis (OM) after carmustine, etoposide, cytosine arabinoside, and melphalan (BEAM) chemotherapy. PV701 mouthwash (15 mL x 13.5 mg/mL) was administered 6 times a day for 12 days, from day--6 to day +5, to patients with lymphoma, who were given BEAM on day--6 to day--2, with autologous stem cells infused on day 0. Dose de-escalation of PV701 was planned if dose-limiting toxicities occurred. The severity and duration of OM, the duration of enteral/parenteral feeding, the requirement for intravenous opiates, and admission to intensive care were recorded. Outcomes were also compared with those of historical control patients. Nine patients received PV701 13.5 mg/mL. PV701 was well tolerated, and no dose-limiting toxicities were observed. Compared with 89 historical controls, the 9 PV701-treated patients had significantly less frequent grade 2 or 3 OM ( P=.0006) and had grade>or=3 OM for an estimated 5 fewer days ( P=.0003). There was a reduction in the need for enteral/parenteral feeding ( P=.012), its duration ( P=.010), and its frequency ( P=.022) and in the duration of intravenous opiates ( P=.0006). We conclude that PV701 mouthwash is readily administered with minimal side effects at a dose of 1215 mg/d, and further investigation of this agent is warranted.

Topics: Adult; Aged; Animals; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cattle; Complex Mixtures; Cytarabine; Dose-Response Relationship, Drug; Female; Growth Substances; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Milk; Mouth Mucosa; Mouthwashes; Podophyllotoxin; Stomatitis

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carmustine; Combined Modality Therapy; Cyclophosphamide; Female; Hodgkin Disease; Humans; Melphalan; Multiple Myeloma; Neoplasms, Second Primary; Prednisone; Procarbazine; Vincristine; Whole-Body Irradiation

The IEV schedule consisted of epirubicin 100 mg/m2 on day 1, etoposide 150 mg/m2 on days 1-3, and ifosfamide 2.5 g/m2 on days 1-3. Patients who proceeded to haematopoietic stem cell transplants (HDTs) received conditioning therapy with BEAM [for the Hodgkin's Lymphoma (HL) and non-Hodgkin's Lymphoma (NHL) groups], or melphalan 100 mg/m2 and mitoxantrone [for the multiple myeloma (MM) patients]. The study consisted of 65 patients with a median age of 53 years: 27 had aggressive NHL, 20 had HL, 7 had indolent NHL, and 11 had MM. Fifty-five patients received IEV for a disease that was refractory to conventional induction regimens, or that was in first or second relapse; 4 patients were treated with IEV while in complete response (CR) after chemotherapy in order to mobilise peripheral blood stem cells (PBSCs). Ninety percent of patients with HL responded to IEV, and 85% achieved CR. Both aggressive and indolent NHLs were less responsive (ORR 50 and 33%, respectively; CRR 41 and 16.5%, respectively). MM patients displayed an intermediate responsiveness (ORR 50% and CRR 30%). IEV was well tolerated in most patients. No life- threatening infections were recorded. PBSC mobilisation was successful in 37 out of 39 patients (95%) and led to the collection of a median of 16, 12, and 13.7 x 10(6) CD34+ cells/kg in patients with HL, NHL, and MM, respectively. All 37 patients underwent an autologous stem cell transplant following a 1 to 2 month interval after the end of IEV. Two patients were submitted to an allogeneic transplant. The median overall survival rate in HL, aggressive NHL, and indolent NHL is 32 (5-60), 16 (2-46), and 14 (4-42) months, respectively. Median EFS is 31 (5-60), 7 (2-46), and 7.5 (4-42) months, respectively. In conclusion, our study confirms that IEV +/- HDT is a well-tolerated and effective salvage treatment for lymphoid malignancies, and that IEV acts as an excellent stem cell mobiliser.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Epirubicin; Etoposide; Female; Hodgkin Disease; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mitoxantrone; Multiple Myeloma; Odds Ratio; Peripheral Blood Stem Cell Transplantation; Podophyllotoxin; Recurrence; Remission Induction; Salvage Therapy; Time Factors; Transplantation Conditioning; Treatment Outcome

Despite high-dose chemotherapy and autografting, the outcome for patients with primary refractory Hodgkin's disease (HD) or multiple relapses remains unsatisfactory. Six pediatric patients (median age: 16 years, range: 11-19) received reduced intensity conditioning and allogeneic peripheral blood stem cell transplantation (PBSCT) after failure of stratified first-line chemotherapy, involved-field radiotherapy, and salvage chemotherapy including autologous PBSCT (two patients). For conditioning, fludarabine was combined with busulfan (8 or 12 mg/kg) and additional cyclophosphamide (three patients), or without cyclophosphamide (two patients), or melphalan (one patient). Two patients died of infections and one of progression. One patient remains in complete remission 59 months following transplantation. Two patients relapsed but responded after withdrawal of immunosuppression, chemotherapy, or donor lymphocyte infusions and are alive at 22 and 36 months post transplant, respectively. Allogeneic PBSCT, with reduced intensity conditioning, may be beneficial for selected patients with refractory HD.

Topics: Adolescent; Antineoplastic Agents; Busulfan; Child; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Female; Graft vs Host Disease; Hodgkin Disease; Humans; Immunosuppressive Agents; Male; Melphalan; Neoplasm Recurrence, Local; Peripheral Blood Stem Cell Transplantation; Remission Induction; Transplantation Conditioning; Treatment Outcome; Vidarabine

Topics: Adult; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Combined Modality Therapy; Cytarabine; Dacarbazine; Dermatomycoses; Dexamethasone; Doxorubicin; Etoposide; Folliculitis; Hodgkin Disease; Humans; Itraconazole; Malassezia; Male; Melphalan; Opportunistic Infections; Vinblastine

Because few patients failing autologous transplantation for Hodgkin's disease survive long-term, we explored reduced-intensity allografts using BEAM conditioning and early withdrawal of immunosuppression as an alternative to palliative chemotherapy. Ten patients with Hodgkin's disease underwent an allograft, receiving either matched sibling peripheral blood stem cells (5), partially matched sibling bone marrow (1), or matched unrelated bone marrow (4). Graft-versus-host disease (GVHD) prophylaxis was mini-methotrexate and FK-506 with weaning at day 60. The median age of patients was 35 years (range: 21 to 49 years). The median time from initial diagnosis was 73 months (range: 12 to 172 months) and from autograft was 49 months (range: 5 to 143 months). One patient was in CR, 5 patients were in partial remission, 3 were in relapse, and 1 patient had primary refractory disease. All patients' transplants engrafted rapidly, and the 100-day mortality was 0. Two patients developed acute GVHD. Five of the 9 patients beyond 100 days have developed mild chronic GVHD, of which 1 case was progressive and required systemic therapy. All 10 responded: 8 complete responses and 2 partial remissions. Three patients have relapsed (at 2, 6, and 8 months, respectively), 1 has died at 4 months. At a mean of 12 months (range: 1 to 21 months) after allograft, 9 of 10 patients are alive, with 7 in continuous remission. BEAM allogeneic transplantation with early reduction in immunosuppression is safe (no treatment-related deaths) and effective in advanced Hodgkin's disease where autografts have failed. A graft versus lymphoma effect appears to be a significant contributing factor in responding patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cytarabine; Etoposide; Female; Graft Survival; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Prospective Studies; Remission Induction; Salvage Therapy; Survival Analysis; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome

The objective of the current study was to evaluate in a multicenter setting the feasibility and efficacy of a high-dose sequential (HDS) chemotherapy regimen that combined intensive debulking and high-dose therapy (HDT) with peripheral blood progenitor cell (PBPC) autografting in patients with refractory or recurrent Hodgkin lymphoma (HL).. Data were collected from 102 patients with HL who were treated with the HDS regimen at 14 centers associated with the Intergruppo Italiano Linfomi. Twenty-four patients had primary refractory HL, 59 patients had their first recurrence of HL (within 1 year in 32 patients and > 1 year in 27 patients), and 19 patients had multiple disease recurrences. The HDS regimen included the sequential delivery of high-dose (hd) cyclophosphamide with PBPC harvesting, methotrexate, etoposide, then HDT (usually hd mitoxantrone plus L-phenylalanine mustard) with PBPC autografting. In addition, radiotherapy was delivered to 36 patients at sites of bulky or persistent disease.. Ninety-two patients (90%) completed the HDS program. There were five toxic deaths (treatment-related mortality rate, 4.9%) and six secondary malignan cies (five patients developed myelodysplastic syndrome/acute myelogenous leukemia, and one patient developed colorectal carcinoma). At a median follow-up of 5 years, the 5-year overall survival (OS) and event-free survival (EFS) projections were 64% (95% confidence interval [95% CI], 54-74%) and 53% (95% CI, 43-63%), respectively. Patients with their first recurrence had the most favorable outcome, with 5-year OS and EFS projections of 77% (95% CI, 66-88%) and 63% (95% CI, 50-76%), respectively. There were no significant differences between patients with early first recurrence and late first recurrence. The poorest outcome was observed in patients with refractory HL, with 5-year OS and EFS projections of 36% (95% CI, 16-55%) and 33% (95% CI, 14-52%), respectively. Patients who received HDS chemotherapy after multiple recurrences had an intermediate outcome. Multivariate analysis showed that refractory disease and systemic symptoms at the time of initial presentation were associated significantly associated with poor OS and EFS.. The use of HDS chemotherapy for patients with refractory and/or recurrent HL is feasible at the multicenter level. The combination of intensive debulking and HDT with PBPC autografting offers a good chance of prolonged disease free survival for patients with their first recurrence of HL.

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Methotrexate; Middle Aged; Mitoxantrone; Prognosis; Transplantation, Autologous; Treatment Outcome

High dose chemotherapy supported with hematopoietic progenitor cells gives a characteristic neutropenic period (blood neutrophils < 0.5 x 10(9) c/l) ranging from 10 to 16 days. The question of a correlation between the CFU-GM content of the transplanted CD34+ cells and time to neutrophil recovery by patients having been given high-dose chemotherapy (HD-CT) with stem cell support was addressed by means of a mathematical model of granulopoiesis. The model utilizes a convection-reaction partial differential equation (PDE) with feedback from a cytokine compartment on proliferation, maturation, and mobilization of granulocytes from bone marrow to blood. The observed number of CFU-GM cells in the transplanted CD34+ cell autograft was used as input to the model. Using this approach, the observed gross relationship between CFU-GM content in the reinfused blood product and engraftment time could be reproduced. At the same time, the effects of assumed physiological mechanisms, especially some of the effects of G-CSF on proliferation rate, maturation rate, mobilization, and cell death, could be investigated and discussed relative to observed engraftment. The model makes it possible to explain how cytokines interfere with progenitor cell mobilization from bone marrow to blood, and it points out the implications of a regulating mechanism for the granulocyte maturation rate.

Topics: Adult; Algorithms; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carmustine; Cell Differentiation; Cell Division; Computer Simulation; Cytarabine; Dose-Response Relationship, Drug; Flow Cytometry; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Kinetics; Leukocytes, Mononuclear; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; Models, Biological; Myelopoiesis; Peripheral Blood Stem Cell Transplantation; Podophyllotoxin; Transplantation, Autologous

Autologous stem cell transplantation (ASCT) is largely employed in primary resistant or recurrent Hodgkin's Lymphoma (HL), while its role early in the course of the disease is still controversial. Our purpose was to analyse the results of 51 high-risk HL patients autografted at our Institution and the role of possible prognostic risk factors for the outcome. Twelve (23.5%) patients were in complete remission at transplant and were transplanted as having an high risk disease; 20 (39.5%) patients were in partial response and 19 (37.0%) were transplanted as primary induction failure. At a median time of 38 (6-111) months from ASCT, 36 (70.5%) patients are alive in complete remission, 8 (15.5%) patients are alive with disease and 7 (14.0%) died for progression. Thirty out of 32 (94.0%) patients transplanted with responsive disease (either complete or partial response) are alive without disease. Six out of 19 (32.0%) patients transplanted with resistant disease are alive in complete remission. The overall survival of the entire population is 77.0% at 60 (14-151) months from diagnosis. Disease free survival of the 22 patients that achieved a complete remission after ASCT (16 in partial response and 6 with resistant disease) is 100%. In our experience, more than 90% of patients transplanted with responsive but high risk disease, seem achieving and maintaining a durable complete remission, and more than 30.0% of patients submitted to ASCT with refractory disease can be potentially rescued by transplant.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Italy; Lymph Nodes; Male; Melphalan; Middle Aged; Prognosis; Remission Induction; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

We report the outcome of reduced-intensity allogeneic progenitor cell transplantation (alloPCT) for 188 patients with lymphoma from the Working Party Lymphoma of the European Group for Blood and Bone Marrow Transplantation (EBMT). The median age of the patients was 40 years, the median number of prior treatment courses was 3, and 48% of patients had undergone a prior autologous transplantation. Eighty-four percent of the patients received conditioning with fludarabine-based regimens and 10% with the BEAM (BCNU, etoposide, cytosine arabinoside, melphalan) protocol. Full donor chimerism was confirmed in 71% of 100 patients assessed. Acute graft-versus-host disease (GVHD) developed in 37% of patients and chronic GVHD in 17%. A disease response to donor leukocyte infusion (DLI) was seen in 10 of 14 patients. With a median follow-up of 283 days, the overall survival rates at 1 and 2 years were 62% and 50%, respectively. The 100-day and 1-year transplantation-related mortality (TRM) rates were 12.8% and 25.5%, respectively, and were significantly worse for older patients. The probability of disease progression at 1 year for patients with chemoresistant and chemosensitive disease were 75% and 25%, respectively (P =.001). The progression-free survival at 1 year was 46% and was significantly better for those with chemosensitive disease, Hodgkin disease (HD), and low-grade non-Hodgkin lymphoma (NHL). Patients with high-grade NHL, mantle cell lymphoma, or chemoresistant disease had a poor outcome. Reduced-intensity progenitor cell transplantation is associated with a reduced TRM and may control advanced HD and low-grade NHL. A longer period of follow-up is required to determine the benefit of DLI and the graft-versus-lymphoma effect.

Topics: Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antilymphocyte Serum; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cohort Studies; Cytarabine; Disease Progression; Drug Resistance, Neoplasm; Europe; Female; Follow-Up Studies; Graft Survival; Graft vs Host Disease; Hodgkin Disease; Humans; Immunosuppressive Agents; Life Tables; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Podophyllotoxin; Proportional Hazards Models; Salvage Therapy; Survival Analysis; Survival Rate; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine

The role of high-dose chemotherapy; with subsequent autologous bone marrow rescue (AutoBMR) for high risk or recurrence of advanced solid tumor was evaluated in 16 children (August 1998-March 2001). At present, 11 (69%) patients are still alive, showing no evidence of the disease, 11-31 mo after therapy (median follow-up of 17 mo). Tumor progression was reported in 5 (31%) at months 5, 6, 8, 9 and 11 (after AutoBMR rhabdosarcoma--3; Ewing's sarcoma--2). Overall and recurrence-free survival among all patients was 74 and 66%, respectively.

Topics: Adolescent; Age Factors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Carboplatin; Carmustine; Child; Child, Preschool; Cytarabine; Dacarbazine; Data Interpretation, Statistical; Disease-Free Survival; Doxorubicin; Female; Follow-Up Studies; Hodgkin Disease; Humans; Infant; Lymphoma, Non-Hodgkin; Male; Melphalan; Podophyllotoxin; Rhabdomyosarcoma; Sarcoma, Ewing; Sex Factors; Statistics, Nonparametric; Time Factors; Transplantation, Autologous; Vinblastine

We have determined the predictive value of [18F]2-fluoro-2-deoxy-glucose (FDG-PET) in patients with Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) scheduled for high-dose therapy with stem cell transplantation (HDT/SCT). Inclusion criteria were the presence of an FDG-PET scan after chemotherapy (ChT) within 8 weeks prior to HDT/SCT and available follow-up data. Sixteen patients (10 NHL and six HD) were observed during a follow-up period of 4 to 28 months (median 13 months). Before SCT, five patients had a negative PET, three were weakly positive, two moderately positive, and six strongly positive. None of the five patients with a negative PET before HDT/SCT relapsed and two of three patients with a weakly positive scan are still in remission after HDT/SCT. Of eight patients with a moderate or high positive PET before HDT/SCT, seven relapsed and one died of early HDT/SCT related complications (P< 0.01). Three of eight relapsing patients died of lymphoma 5 to 10 months after SCT and in one additional patient not responding to HDT/SCT, the main cause of death was chronic toxicity 4 months after transplantation. After 12 months, in PET-negative patients the overall and relapse-free survival was 100%, in PET-positive patients 55% and 18%, respectively. In NHL, two patients with negative PET, but with an age-adjusted international prognostic index (AaIPI) of 2 and one with AaIPI = 1 are still in remission. In the seven PET-positive subjects, one patient with AaIPI = 0, three with AaIPI = 1, and two with AaIPI = 2 relapsed. We conclude that FDG-PET is accurate in the prediction of relapse prior to HDT/SCT in patients with lymphoma. It provides additional information when compared with the AaIPI.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Disease-Free Survival; Etoposide; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Podophyllotoxin; Prognosis; Radiopharmaceuticals; Survival Analysis; Survival Rate; Tomography, Emission-Computed; Transplantation Conditioning; Treatment Outcome; Whole-Body Irradiation

Several studies have focused on investigation of the optimal salvage regimen to induce maximum response before autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin's disease (HD). However, in most of these studies, the follow-up is relatively short. In the present study, we report on long-term results of 55 consecutive patients with HD who received Mini-BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] as salvage therapy before ASCT. Eleven patients were refractory to front-line therapy, 17 were partial responders, and 27 patients had relapsed from HD. Twenty-eight patients achieved complete response, and 18 achieved partial response with a median of two cycles of Mini-BEAM, giving a total response rate of 84%. Significant factors predicting poor response (P < 0.05) were: initial treatment with MOPP (mechloroethamine, oncovin, procarbazine, prednisolone), > or = two previous chemotherapy regimens and three disease characteristics at Mini-BEAM treatment: presence of B symptoms, extranodal involvement or low serum albumin. However, only the last two factors retained independent influence on multivariate analysis. In total, 45/55 patients have been transplanted. Median follow-up after Mini-BEAM administration for living patients is 68 months. At the time of reporting, 31 out of 55 patients (56.4%) are still alive, 21 patients (38%) have relapsed, three (5.4%) have developed secondary neoplasias, and five have died of other complications not related to disease progression. The actuarial 7-year overall survival (OS) was 52%, the progression-free survival (PFS) 54% and the event-free survival (EFS) 36%. The response to Mini-BEAM was the most important prognostic factor for predicting the long-term probability of surviving the disease: none of the eight patients who did not respond to Mini-BEAM were alive at 3 years. On multivariate analysis, response to Mini-BEAM and extranodal involvement before Mini-BEAM had a significant influence on OS. Our results show the safety and efficacy of Mini-BEAM before ASCT for refractory or relapsed HD patients.

Topics: Adolescent; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Blood Sedimentation; Carmustine; Cytarabine; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Podophyllotoxin; Prognosis; Recurrence; Salvage Therapy; Sex Factors; Survival Analysis; Transplantation, Autologous

Residual mediastinal masses are frequently observed in patients with Hodgkin disease (HD) after completed therapy, and the discrimination between active tumor tissue and fibrotic residues remains a clinical challenge. We studied the diagnostic value of metabolic imaging by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting active mediastinal disease and predicting relapse. Twenty-eight HD patients with a residual mediastinal mass of at least 2 cm after initial therapy or after salvage chemotherapy were prospectively assigned to 29 examinations with FDG PET and were evaluated as 29 "subjects." Patients were monitored for at least 1 year after examination and observed for signs of relapse. Median follow-up was 28 months (range, 16 to 68 months). A PET-negative mediastinal tumor was observed in 19 subjects, of whom 16 stayed in remission and 3 relapsed. Progression or relapse occurred in 6 of 10 subjects with a positive PET, whereas 4 subjects remained in remission. The negative predictive value (negative PET result and remission) at 1 year was 95%, and the positive predictive value (positive PET result and relapse) was 60%. The disease-free survival for PET-negative and PET-positive patients at 1 year was 95% and 40%, respectively. The difference was statistically significant. A negative FDG PET indicates that an HD patient with a residual mediastinal mass is unlikely to relapse before 1 year, if ever. On the other hand, a positive PET result indicates a significantly higher risk of relapse and demands further diagnostic procedures and a closer follow-up.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Dexamethasone; Diagnosis, Differential; Disease-Free Survival; Doxorubicin; Etoposide; False Negative Reactions; False Positive Reactions; Fibrosis; Fluorodeoxyglucose F18; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Life Tables; Mediastinal Neoplasms; Melphalan; Neoplasm Recurrence, Local; Predictive Value of Tests; Prednisone; Procarbazine; Prospective Studies; Radiopharmaceuticals; Radiotherapy, Adjuvant; Remission Induction; Salvage Therapy; Tomography, Emission-Computed; Transplantation, Autologous; Vinblastine; Vincristine

Register data suggest that patients with Hodgkin's disease (HD) given high-dose therapy (HDT) with peripheral blood progenitor cells (PBPC) have a less favourable prognosis as compared to those given bone marrow as stem cell support. Since this can be due to infusion of tumour cells contaminating the PBPC grafts, we initiated a feasibility study in which PBPC grafts from HD patients were purged by CD34(+) cell enrichment. Controversy exists about whether the use of CD34(+) enriched stem cells leads to a delayed haematological and immune reconstitution. We compared these parameters, including risk of infections and clinical outcome after HDT, in patients with HD given either selected CD34(+) cells or unmanipulated PBPC as stem cell support. From October 1994 to May 2000, 40 HD patients with primary refractory disease or relapse were treated with HDT and supported with either selected CD34(+) cells (n = 21) or unmanipulated PBPC (n = 19) as stem cell support. All patients had chemosensitive disease at the time of transplantation. A median of 5.8 (range 2.7-20.0) vs 4.5 (range 2.3-17.6) x 10(6) CD34(+) cells per kilo were reinfused in the CD34(+) group and PBPC group, respectively. No difference was observed between the two groups with regard to time to haematological engraftment, reconstitution of B cells, CD56(+) cells and T cells at 3 and 12 months and infectious episodes after HDT. Two (5%) treatment-related deaths, one in each group, were observed. The overall survival at 4 years was 86% for the CD34(+)group and 74% for the PBPC group with a median follow-up of 37 months (range 1-61) and 46 months (range 4-82), respectively (P = 0.9). The results of this study demonstrate that the use of CD34(+) cells is safe and has no adverse effects either with respect to haematological, immune reconstitution or to infections after HDT.

Topics: Adolescent; Adult; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Etoposide; Feasibility Studies; Female; Follow-Up Studies; Graft Survival; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Infections; Male; Melphalan; Middle Aged; Neutropenia; Radiotherapy, Adjuvant; Retrospective Studies; Risk; Safety; Salvage Therapy; Survival Analysis; Survival Rate; Transplantation Conditioning; Treatment Outcome

Systemic mycosis is among the most feared opportunistic infections in the immunocompromised host. Difficulty and delay in diagnosis and treatment often result in poor outcomes. In this communication a metastatically spreading form of subcutaneous aspergillosis developed in a patient with a history of allogeneic stem cell transplantation for relapsed Hodgkin's lymphoma. Strikingly, necrotizing cutaneous papules or ulcerating lesions were absent. Diagnosis was accomplished after excision of a clinically non-suggestive subcutaneous nodule. Despite prompt initiation of antimycotic therapy the outcome was fatal; dosage of conventional and liposomal amphotericin B was limited due to treatment-related toxicities. This case report describes a novel form of aspergillosis and underlines the need for an aggressive diagnostic approach in severely immunocompromised patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bleomycin; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Deoxycytidine; Dexamethasone; Doxorubicin; Etoposide; Fatal Outcome; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases, Fungal; Male; Melphalan; Neoplasm Recurrence, Local; Opportunistic Infections; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prednisone; Procarbazine; Salvage Therapy; Skin; Transplantation, Homologous; Vinblastine; Vincristine

The use of autologous peripheral blood progenitor cells (PBPC) expedites hematologic recovery and reduces the costs of transplantation in comparison with autologous bone marrow; however, its efficacy in patients with Hodgkin's disease has been questioned. We evaluated the results of autologous PBPC transplantation in a population of unselected and uniformly treated patients with primary refractory or relapsed Hodgkin's disease.. Forty consecutive adult patients with primary refractory (n = 7) or relapsed (n = 33) Hodgkin's disease received high-dose BEAM (BCNU, etoposide, ara-C, and melphalan) followed by autologous PBPC infusion. Twenty-four patients (60%) received high-dose BEAM as outpatients. Consolidative radiation therapy was administered to 14 patients (35%).. Thirty-seven patients (92%) achieved a post transplant complete response. The 3-year progression-free survival (PFS) was 69%, and the 3-year overall survival (OS) was 77%, with a median follow-up of surviving patients of 28 months. Severe non-hematologic toxicities included gastrointestinal side effects (diarrhea 17%, mucositis 25%), and interstitial pneumonitis (15%). One patient died of acute transplant-related complications (mortality rate 2.5%). Strong predictors of poor PFS were chemoresistant versus chemosensitive/untested disease (actuarial PFS 89% versus 22%, P = 0.0000) and stage IIB-IV versus I-IIA at relapse/progression (86%, versus 46%, P = 0.005). All five patients with elevated lactate dehydrogenase at the time of transplantation died of their disease. There was a trend toward worse PFS for patients receiving a higher number of CD34+ cells (> or = 11 x 10(6) per kg).. High-dose BEAM chemotherapy with autologous PBPC transplantation is associated with low mortality and results in satisfactory PFS for patients with primary refractory or relapsed Hodgkin's disease. The subset of patients with progressive disease at the time of transplantation performs poorly and may benefit from alternative strategies.

Topics: Adolescent; Adult; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; L-Lactate Dehydrogenase; Male; Melphalan; Middle Aged; Prognosis; Recurrence; Transplantation, Autologous

We previously reported a 50% (95% CI = 33-76%) 5 year event-free survival (EFS) rate for 23 patients with Hodgkin's disease (HD) who received salvage therapy with single agent high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT). Predictors of poor outcome included bulky disease and initial remission <1 year. Since 1995, similar poor prognosis patients have been treated with double high-dose therapy consisting of dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2, cisplatin 105 mg/m2 (DICEP) for tumor cytoreduction and stem cell mobilization followed by HDM/ASCT. The purpose of the present study is to determine if the use of DICEP is associated with improved event-free (EFS) and overall survival (OAS) for patients treated with HDM/ASCT. From February 1981 to June 1999, 46 consecutive patients received HDM/ASCT for relapsed (n = 35) or refractory (n = 11) HD. DICEP re-induction and blood stem cell mobilization was used for 21 patients. Factors considered for univariate and multivariate analyses included age at transplant, number of failed chemotherapy regimens, prior radiotherapy, length of initial remission, relapsed or refractory disease status, extranodal relapse, B symptoms at relapse, bulk, post-ASCT radiotherapy, and DICEP re-induction therapy. Cox proportional hazards models were constructed for both event and death. DICEP and HDM were well tolerated with no early treatment-related mortality or toxicity requiring life-sustaining measures. For all 46 patients, the projected 5 year EFS was 52% (95% CI = 38-72%) and OAS was 57% (95% CI = 40-82). Factors independently associated with relapse in multivariate analysis included bulk >5 cm (RR = 6.38, P = 0.002), prior radiotherapy (RR = 3.59, P = 0.027), and not using DICEP (RR = 5.29, P = 0.005). Factors independently associated with death included bulk >5 cm (RR = 5.13, P = 0.009), > or =3 prior chemotherapy regimens (RR = 4.72, P = 0.019), and not using DICEP (RR = 7.49, P = 0.015). This study demonstrates that DICEP re-induction prior to HDM/ASCT is feasible. The preliminary data are sufficiently encouraging to warrant a multicenter phase II or a phase III trial evaluating DICEP followed by HDM/ASCT as salvage therapy for HD.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Component Removal; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Etoposide; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Melphalan; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Risk Factors; Survival Rate; Transplantation, Autologous; Treatment Outcome

To achieve a maximal complete remission rate in patients with recurrent and refractory Hodgkin's disease. To find out a group of patients in whom surgical removal of the residual mediastinal mass would be most effective.. 46 patients with Hodgkin's disease received Dexa-BEAM chemotherapy followed by radiotherapy. Surgical removal of the residual mediastinal mass was made in 12 patients.. Second-line Dexa-BEAM therapy produced a 50% complete remission rate. Overall survival was 45.5%, the disease-free survival--43.5%. Removed mediastinal masses were indicative of Hodgkin's disease in 7 cases and fibrosis in 4 cases.. Dexa-BEAM is an effective program in the treatment of recurrent and refractory Hodgkin's disease. Surgical removal of the residual mediastinal mass with radiotherapy and high-dose chemotherapy improves prognosis in very unfavorable, primary progressive form of Hodgkin's disease.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Chemotherapy, Adjuvant; Cytarabine; Dexamethasone; Etoposide; Female; Hodgkin Disease; Humans; Male; Mediastinal Neoplasms; Melphalan; Middle Aged; Neoplasm, Residual; Prognosis; Radiotherapy, Adjuvant; Recurrence; Salvage Therapy

High dose chemotherapy and autologous stem cell transplantation are widely used in relapsed and primary refractory Hodgkin's disease. We transplanted 42 patients with Hodgkin's disease between 1990-1998. Median follow-up was 31 months (range 1-102). 29 (69%) were transplanted after relapse and 13 (31%) were refractory to first line therapy. Median age at transplantation was 29 years (range 19-58) and 23 (55%) were males. All were treated with the BEAM protocol (carmustine, etoposide, cytarabine and melphelan). 18 who were in remission received radiotherapy following transplantation. The source of the stem cells was bone marrow in 17% and peripheral blood in 83%. At initial diagnosis: 57% had stage III-IV disease and B symptoms were present in 52%. 75% were treated with MOPP, ABVD or with related versions. Radiotherapy followed in 52%. Prior to transplantation, 45% of the relapsed group were in the advanced stage. 33% and 12% of all patients had lung and bone involvement, respectively. The complete remission rate was 86% for the 2 groups. 2 (5%) died from transplant-related complications and MDS/AML developed in 2 (5%) after transplantation. The 3-year overall survival (OS) and disease-free survival (DFS) were 68% and 60%, respectively. The 3-year OS for the relapsed group was 64% compared with 76% for the refractory group, and the 3-year DFS for the relapsed group was 60% vs. 42% for the refractory group (neither difference significant). Radiotherapy following transplantation did not have a beneficial effect on DFS. No prognostic factors for outcome of transplantation were found, most probably due to the limited number of patients and the high variability of disease characteristics. We conclude that high dose chemotherapy and autologous stem cell transplantation are effective and relatively safe for relapsed or primary refractory Hodgkin's disease. The DFS at 3 years was longer for those transplanted after relapse than those with primary refractory disease, but not significantly. Patients with primary refractory disease can be salvaged with high dose chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Combined Modality Therapy; Cytarabine; Dacarbazine; Doxorubicin; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Mechlorethamine; Melphalan; Middle Aged; Podophyllotoxin; Prednisone; Procarbazine; Recurrence; Retrospective Studies; Survival Rate; Time Factors; Vinblastine; Vincristine

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Blood Component Removal; Combined Modality Therapy; Disease-Free Survival; Female; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multiple Myeloma; Portugal; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies

In 1995-1999, 67 patients with relapsed Hodgkin's disease or refractory to chemotherapy (group A--first relapse, B--primary refractory disease, and C--repeated relapse) received cytoreductive (dexaBEAM, DHAP) therapy followed by high-dose BEAM chemotherapy and autologous bone marrow or blood cell transplantation. Early postoperative transplant-related mortality rate was 4.5%. At day 100, complete remission rates were: group A--95.6%; B--74.1%; and C--76.5%. Survival for all patients was: overall--61.9%; event-free--43.9%; disease-free--46%; and relapse-free survival--49.5%. Such factors as primary refractory disease, age over 30 years and response to cytoreductive therapy had significant influence on overall survival prognosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cytarabine; Dexamethasone; Drug Administration Schedule; Drug Resistance, Neoplasm; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Retrospective Studies; Risk Factors; Survival Analysis; Transplantation, Autologous; Treatment Outcome

The aim of this study was to assess the relationship between radiation therapy (RT) and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT) for recurrent/refractory Hodgkin's disease (HD). Between December 1986 and December 1992, 59 patients previously treated at the Princess Margaret Hospital underwent HDCT (etoposide 60 mg/kg, melphalan 160 mg/m2) and ABMT, performed for refractory (13 patients) or relapsed (46 patients) HD. RT was incorporated in the salvage treatment with the intent to achieve complete control of disease prior to ABMT. RT was given before ABMT in 33 patients, and after ABMT in 4 patients. Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. With a median follow-up of 4.6 years (range 1.2-7.4 years), the actuarial overall survival was 41% +/- 14% at 5 years. We observed 37 deaths, and 10 of these were TR deaths. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, 3 of these solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure with complicating sepsis as a major medical problem. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 survivors (mean 105 days; range 0-263 days) (P = 0.026). Among 9 patients with ABMT within 50 days of thoracic RT, 6 had TR death. In contrast, among the 35 patients without thoracic RT (26 no RT, 9 non-thoracic RT), there were only 2 TR deaths. The 4 patients treated with mantle RT post-ABMT had no serious pulmonary complications. The use of thoracic RT before HDCT and ABMT was associated with a high post-transplant mortality rate. It was most evident in patients who received thoracic RT within 50 days prior to ABMT, or when the target volume included large volume of lung. We recommend that the use of post-transplant RT be investigated to decrease TR mortality.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Chronic Disease; Combined Modality Therapy; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Prognosis; Radiotherapy; Recurrence; Survival Analysis; Transplantation, Autologous

A retrospective analysis was performed on 100 patients with non-Hodgkin's lymphoma (NHL, n = 75) or Hodgkin's disease (HD, n = 25) who underwent peripheral blood progenitor cell transplant (PBPCT) following high-dose chemotherapy (HDCT) with BCNU, etoposide, cytarabine and melphalan (BEAM) between March 1994 and June 1997. Following PBPCT and until engraftment all patients received oral ciprofloxacin and fluconazole, patients with positive Herpes simplex virus serology received acyclovir and 91 patients received filgrastim. The median days of neutropenia and days to an absolute neutrophil count (ANC) >500/mm3 were 6 and 9, respectively. Febrile neutropenia occurred in 68 patients. Gram-positive bacteremia occurred in 14 patients. No gram-negative infections, invasive fungal infections, intensive care visits or deaths occurred during the period of neutropenia or in the first 30 days following transplant. In multivariate logistic regression the risk of development of any infection was associated only with the duration of neutropenia (P = 0.02) and the risk of bacteremia was associated only with the number of CD34+ cells infused (P = 0.046). Among 49 patients treated in the outpatient setting, 14 (28%) were never admitted. High-dose chemotherapy with BEAM supported by PBPCT, prophylactic antibiotics and filgrastim resulted in a low incidence of infections and no acute mortality. WBC engraftment occurred rapidly allowing for a predictable course during which lengthy hospital stays and amphotericin therapy could be avoided.

Topics: Adult; Ambulatory Care; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Dose-Response Relationship, Drug; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; Neutropenia; Podophyllotoxin; Retrospective Studies

Hodgkin's disease is curable in the majority of patients, although a proportion of patients are resistant to or relapse after initial therapy. High-dose therapy with autologous stem cell support has become the standard salvage therapy for patients failing chemotherapy, but there have been reports of a high incidence of myelodysplasia/acute myeloid leukaemia (MDS/AML) following such treatment. Patients who receive such therapy form a selected group, however, who have already been subjected to other leukaemogenic factors, such as treatment with alkylating agents. In order to ascertain the true risk of MDS/AML, comparison must be made with other patients subjected to the same risks but not undergoing transplantation. We report a retrospective comparative study of 4576 patients with Hodgkin's disease from the BNLI and UCLH Hodgkin's databases, which includes 595 patients who have received a transplant. Statistical analysis including Cox's proportional hazards multivariate regression model with time-dependent covariates was employed. This analysis reveals that the risk of developing MDS/AML was dominated by three factors, namely quantity of prior therapy (relative risk [RR] 2.01, 95% confidence intervals [CI] 1.49-2.71, for each treatment block, P < 0.0001) and whether the patient had been exposed to MOPP (RR 3.61, 95% CI 1.64-7.95, P = 0.0009) or lomustine chemotherapy (RR 4.53, 95% CI 1.96-10.44, P = 0.001). Following adjustment for these factors in the multivariate model the relative risk associated with transplantation was 1.83 (95% CI 0.66-5.11, P = 0.25). This study provides no evidence of a significantly increased risk of MDS/AML associated with BEAM therapy and autologous transplantation in Hodgkin's disease. Concern over MDS/AML should not mitigate against the timely use of this treatment modality.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Child, Preschool; Chlorambucil; Cohort Studies; Combined Modality Therapy; Cytarabine; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Incidence; Infant; Leukemia, Myeloid; Life Tables; Lomustine; Male; Mechlorethamine; Melphalan; Middle Aged; Myelodysplastic Syndromes; Neoplasms, Second Primary; Podophyllotoxin; Prednisolone; Prednisone; Procarbazine; Retrospective Studies; Risk; Salvage Therapy; Vinblastine; Vincristine

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antigens, Neoplasm; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Cyclophosphamide; Cytarabine; Dacarbazine; Dexamethasone; Doxorubicin; Drug Resistance, Neoplasm; Etoposide; Hodgkin Disease; Humans; Idarubicin; Ifosfamide; Immunization, Passive; Interleukin-2; Male; Melphalan; Middle Aged; Prednisone; Procarbazine; Remission Induction; Rituximab; Salvage Therapy; Vinblastine; Vincristine

Limited information is available regarding the cardiac and pulmonary effects of high dose chemotherapy (HDCT) and autologous peripheral blood progenitor cell (PBPC) transplantation.. The authors evaluated cardiac and pulmonary function after BEAM (BCNU 300 mg/m2, etoposide 400 mg/m2/day x 3 days, cytosine arabinoside 200 mg/m2/day x 4 days, and melphalan 140 mg/m2), HDCT, and PBPC transplantation in 26 patients with non-Hodgkin's lymphoma or Hodgkin's disease. Therapy prior to BEAM included doxorubicin (25 patients), bleomycin (6 patients), and mediastinal irradiation (4 patients). All patients had pulmonary function tests (PFTs) and equilibrium radionuclide angiography before and at a median of 57 weeks after transplantation.. Prior to high dose therapy, 8 patients had abnormal PFTs, including 6 with a diffusing capacity of the lung for carbon monoxide (DLCO) <70% of predicted value. At the time of reevaluation after HDCT, all patients included in the study were in complete remission, and none had received additional therapy after transplantation. At a median of 77 weeks after transplantation, none of the patients had cardiac or pulmonary symptoms. Moreover, there were no significant changes in total lung capacity, forced vital capacity, forced expiratory volume in 1 second/forced vital capacity, DLCO, or left ventricular ejection fraction values when compared with baseline studies.. The authors concluded that HDCT with BEAM and PBPC transplantation did not result in significant cardiac or pulmonary toxicity, even in patients with borderline pretransplantation PFT values. Further studies of patients undergoing HDCT and PBPC transplantation are needed.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Female; Heart; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lung; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neutropenia; Neutrophils; Podophyllotoxin; Respiratory Function Tests; Retrospective Studies; Ventricular Function, Left

Many centers use CY and G-CSF to mobilize PBPC. In this study we explored whether a standard chemotherapy regimen consisting of mitoguazon, ifosfamide, MTX and etoposide (MIME) combined with G-CSF was capable of mobilizing PBPC in lymphoma patients. Twelve patients with Hodgkin's disease (HD) and 38 patients with non-Hodgkin's lymphoma (NHL) were mobilized with MIME/G-CSF. Most patients were heavily treated with different chemotherapy regimens receiving a median of 11 cycles (range 3 to 20) of chemotherapy prior to mobilization. It was found that the optimal time of PBPC harvest was at days 12 and 13 after initiating the mobilization regimen. The median number of collected CD34+ cells per kg body weight was 7.1 x 10(6) (range 0.5-26.2). More than 2.0 x 10(6) CD34+ cells/kg were achieved in 69% of the patients after one apheresis. When additional cycles of apheresis were done, only 6% failed to harvest this number of CD34+ cells. There was a statistically significant inverse correlation between the number of prior chemotherapy cycles and CD34+ cell yield (P = 0.003). No such association was found between CD34+ cell yield and prior radiotherapy. When MIME/G-CSF was compared with Dexa-BEAM/G-CSF, it was found that MIME/G-CSF tended to be more efficient in mobilizing PBPC in spite of being less myelotoxic. All patients transplanted with MIME/G-CSF mobilized PBPC had fast and sustained engraftment. These results demonstrate that an ordinary salvage chemotherapy regimen, such as MIME combined with G-CSF can be successfully used to mobilize PBPC.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Dexamethasone; Etoposide; Female; Graft Survival; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Mitoguazone; Salvage Therapy; Time Factors

The purpose of this study was to determine the effectiveness of second mobilization strategies in patients who yielded < 2.5 x 10(6) CD34+ PBSC/kg after initial mobilization. Repeat mobilization attempts were made with chemotherapy and G-CSF (n = 61) or G-CSF alone (n = 58) in patients who failed initial mobilization with chemotherapy and G-CSF (n = 92) or G-CSF alone (n = 27). A median of 0.27 x 10(6) CD34+ cells/kg per apheresis was collected after the second mobilization, compared with 0.16 with initial harvests (p = 0.0001). Forty-eight percent achieved a target CD34+ cell dose > or = 2.5 x 10(6)/kg when harvests from the first and second mobilizations were combined. Fifteen of 17 patients (88%) with > or = 1.5 x 10(6) CD34+ cells/kg harvested after first mobilization had > or = 2.5 x 10(6) CD34+ cells/kg collected when first and second harvests were combined, as compared with 42 of 102 (41%) achieving < 1.5 x 10(6) CD34+ cells/kg with first PBSC harvests (p = 0.0001). Second mobilizations with chemotherapy and G-CSF or G-CSF alone resulted in similar CD34+ cell yields. Toxicities of second mobilizations were comparable with those of first mobilizations. Seventy-nine patients (66%) received high-dose chemotherapy with PBSC support, with recovery of neutrophils and platelets in a median of 11 and 15 days, respectively. Transplant-related mortality was 4%, and event-free survival at 2 years was 0.34. It was concluded that second mobilization attempts in patients who fail to achieve > or = 2.5 x 10(6) CD34+ cells/kg on initial mobilization were successful in 48% of patients. G-CSF alone was as effective as chemotherapy plus G-CSF in mobilizing CD34+ cells and was associated with less morbidity.

Topics: Adult; Antigens, CD; Antigens, CD34; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Cytapheresis; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Staging

Twenty patients with resistant and relapsed Hodgkin's disease were included into this investigation. The treatment effectiveness and regimen-related toxicity of BEAM-protocol were evaluated. Stem cell transplantation (SCT) was carried out either as bone marrow transplantation (BMT) in 11 patients or peripheral blood stem cell transplantation (PBSCT) in 9 patients. A comparison of the results pointed to a significant decrease in neutropenia duration, fewer blood transfusions needed and shorter stay in hospital in the PBSCT group. Complete remission was observed in 90% of patients of the SCT group, 91%-in BMT and 89%-PBSCT groups. It was found that high-dose chemotherapy followed by SCT is more effective in the treatment of resistant and relapsed Hodgkin's disease and, in certain situations, it is a treatment of choice. As to the toxicity of BEAM-protocol, it does not exceed those of the other chemotherapy modalities used in SCT.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Carmustine; Child; Cytarabine; Female; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Length of Stay; Male; Melphalan; Podophyllotoxin; Recurrence; Treatment Outcome

In the present paper, we evaluate tolerability, outcome and prognostic factors in patients with poor prognosis non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) when uniformly treated with BCNU, etoposide, cytarabine and melphalan (BEAM) and autologous stem cell transplant (ASCT). On hundred and forty-eight patients with NHL (n = 112) or HD (n = 36) received BEAM followed by infusion of bone marrow (n = 55), peripheral blood stem cells (n = 79) or both (n = 14). Twenty-eight patients had low-grade lymphoma (LGL), 68 intermediate- and 16 high-grade lymphoma (IGL). Within the NHL group, 21 patients were in 2nd or subsequent complete remission (CR) at transplant, 34 had sensitive disease and 11 resistant disease; 46 patients were transplanted in 1st CR due to the presence of > or = 2 adverse prognostic features at diagnosis or to a slow CR. Of the HD patients at transplant 17 had active disease, 16 were in > or = 2 CR and three in 1st CR. The overall percentage of toxic deaths was 5.4%, while in the group of patients transplanted with PBSC it was only 1.3%. NHL patients: 78% were in CR following ASCT, including 25 out of 45 patients (56%) who were transplanted with active disease. Only two of the 11 patients transplanted with resistant disease achieved CR. Incidence of overall survival (OS) and disease-free survival (DFS) at 3 years was 65 and 75%, respectively. As far as histology was concerned, OS was significantly better for patients with LGL in comparison with IGL (88 vs 56%) (P = 0.002). DFS was significantly higher for patients transplanted in first CR or first partial remission (PR) than it was for those transplanted in a later CR or PR (86 vs 53%) (P = 0.02). Multivariate analysis for OS showed that histology, bulky disease, poor performance status at transplant and achievement of CR were independent prognostic factors. In addition, a high number of infused MNC was associated with poor DFS. HD patients: 30 (83%) were in CR after transplantation, with 25 maintaining CR at the end of the study. Only one of the four patients transplanted with resistant disease reached CR. Incidence of OS and DFS at 3 years was 78 and 81%. DFS was similar for patients transplanted with early or late relapse (95 and 93%). With multivariate analysis, the only independent variable for OS was CR after transplant. In conclusion, the present results demonstrate the efficacy and low toxicity of the BEAM regimen in high-risk lymphoma patients with sensitive disease. Other

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Child; Child, Preschool; Cytarabine; Female; Graft Survival; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Prognosis; Treatment Outcome

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Prognosis; Remission Induction; Transplantation Conditioning; Transplantation, Autologous

The purpose of this study was to evaluate the efficacy of high-dose chemotherapy with busulfan (Bu), melphalan (Mel), and thiotepa (TT), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or relapsed Hodgkin's disease (HD). Forty patients, 23 with intermediate (n= 18) or high-grade (n=5) NHL and 17 with HD received Bu (12 mg/kg), Mel (100 mg/kg), TT (450-500 mg/m2) [corrected], and autologous PBSC infusion. Of 27 patients with more advanced disease, 16 had primary refractory disease, 8 were in refractory relapse, and 3 were in third remission. Of 13 patients with less advanced disease, 7 were in untreated or responding first relapse and 3 were in second remission, whereas 3 with high-grade NHL were in first remission. Twenty-nine patients (73%) had received prior radiotherapy (RT) prohibiting a total-body irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival, and relapse for all patients were 0.60, 0.46, and 0.31 (0.85, 0.85, and 0.15 for patients with less advanced disease and 0.48, 0.30, and 0.37 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.17. Severe idiopathic pneumonia syndrome was not observed in any patients with less advanced disease and in only one patient with more advanced disease. A regimen of BuMelTT is well tolerated in patients with aggressive NHL or relapsed HD, and results obtained to date are at least equivalent to other published regimens, including TBI-based regimens. This regimen appears to be a particularly attractive alternative for patients who have already received dose-limiting RT and should be evaluated further in prospective, randomized studies.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Combined Modality Therapy; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Remission Induction; Salvage Therapy; Survival Analysis; Thiotepa; Transplantation Conditioning; Treatment Outcome; Whole-Body Irradiation

Eighteen patients with relapsed or refractory Hodgkin's disease (HD) have been treated with high-dose chemotherapy (BEAM regimen) followed by autologous peripheral stem cells and/or bone marrow rescue. There were no treatment-related deaths. Overall response rate was 82%. With a median follow-up of 10 months (3-24 months) overall survival and freedom from progression were 100 and 94% (95% confidence interval 58-97%), respectively. The use of peripheral stem cells in addition to bone marrow resulted in a significant shortening of the time to engraftment (p < 0.01). The BEAM regimen is an effective conditioning schedule which is well tolerated.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Prognosis; Radiotherapy, Adjuvant; Recurrence; Remission Induction; Transplantation, Autologous

We studied the pharmacokinetics and toxicity of 220 mg/m2 melphalan (HDM 220) followed by autologous stem cell transplantation in 16 patients with advanced haematological malignancies. Pharmacokinetic parameters (mean values of steady-state volume of distribution 14.6 l/m2, total body clearance 313 ml/min/m2, elimination half-life 46 min) were the same as those of 140 or 200 mg/m2 melphalan in previous reports. HDM 220 was feasible. Extramedullary toxicity was mainly W.H.O. grade 4 mucositis (13/16 patients). The median duration of 41 d (10, not reached) of thrombocytopenia < 25 x 10(9)/l was long. In multiple myeloma the response rate was 89% in heavily pretreated patients, suggesting that HDM 220 could be considered earlier in the course of the disease as an alternative consolidation therapy.

Topics: Adolescent; Adult; Combined Modality Therapy; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Melphalan; Multiple Myeloma; Pilot Projects; Transplantation, Autologous

Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many patients with relapsed or refractory lymphoma are candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be taken into account. In a retrospective study, we have analyzed the influence of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other factors. Progenitor cells were collected from 96 patients with HD or high-grade NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose chemotherapy. Compared with patients autografted with BM, hematopoietic recovery was significantly accelerated in recipients of PBPC. For PBPC, the number of Dexa-BEAM cycles ( > or = v > 1) was the predominate prognostic factor affecting colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P = .0001), CD34+ cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery to > 0.5 x 10(9)/L (9 v. 11 days, P = .0086), platelet recovery to > 20 x 10(9)/L (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation (190 v 107 x 10(9)/L, P = .031) using univariate analysis. Previous radiotherapy was associated with significantly lower CFU-GM and CD34+ cell yields but had no influence on engraftment. Patient age, patient sex, disease activity, or chemotherapy other than Dexa-BEAM did not have any prognostic impact. Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding factor adversely influencing CFU-GM yield (P < .0001), CD34+ cell yield (P < .0001), and platelet engraftment (P < .0001). BM grafts were not significantly affected by previous Dexa-BEAM chemotherapy or any other variable tested. However, prognostic factors favoring the use of BM instead of PBPC were not identified using joint regression models involving interaction terms between the graft type (PBPC or BM) and the explanatory variables investigated. We conclude that, in contrast to previous radiotherapy or other chemotherapy, exposure to salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is a critical factor adversely affecting yields and performance of PBPC grafts. Marrow progenitor cells appear to be less sensi

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Blood Cells; Bone Marrow; Bone Marrow Transplantation; Carmustine; Cell Survival; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Female; Glyoxal; Graft Survival; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multivariate Analysis; Prednimustine; Prednisolone; Prednisone; Procarbazine; Radiotherapy; Retrospective Studies; Salvage Therapy; Vinblastine; Vincristine

Administration of high-dose cytotoxic therapy with autologous bone marrow transplantation (BMT) results in prolonged cytopenia and significant morbidity and mortality. Several groups have reported that the administration of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with delayed haematological recovery following autologous BMT may accelerate neutrophil recovery and decrease mortality. We have determined the prevalence and natural history of delayed neutrophil recovery following BEAM chemotherapy and autologous BMT for malignant lymphoma in 261 patients treated at a single institution without the use of haemopoietic growth factors. Forty of 261 (15%) patients took > 28 days to reach an absolute neutrophil count (ANC) > 0.5 x 10(9)/L; 29 of these 40 (73%) with delayed engraftment reached an ANC > 0.5 x 10(9)/L by day +42. Five patients with delayed engraftment died before day +100, two of progressive lymphoma, one from unirradiated blood product-related GVHD and two of interstitial pneumonitis (IP). The patients with IP had negative culture and bronchoscopic examinations and onset of assisted ventilation was day +15 and +18, respectively. These results show a high rate of relatively rapid spontaneous recovery in individuals with delayed neutrophil recovery after BEAM plus autologous BMT with a low incidence of death from infection.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cell Count; Combined Modality Therapy; Cytarabine; Etoposide; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; Neutropenia; Opportunistic Infections; Survival Analysis

Conditioning regimens for allogeneic bone marrow transplantation are designed to eradicate malignant cells and to provide sufficient immunosuppression for engraftment of donor marrow. Total body irradiation and high-dose cyclophosphamide are the most established immunosuppressive agents used for this purpose. It is uncertain whether other alkylating agent-based conditioning regimens are sufficiently immunosuppressive to allow engraftment of allogeneic marrow. We report four patients who had prompt engraftment after conditioning with melphalan-based chemotherapy regimens (BEAM or busulfan/melphalan). Two patients survived without disease for a prolonged period, indicating that these melphalan regimens are sufficiently immunosuppressive to allow sustained engraftment and donor hematopoiesis.

Topics: Adult; Bone Marrow Transplantation; Female; Graft Rejection; Hodgkin Disease; Humans; Male; Melphalan; Precursor Cell Lymphoblastic Leukemia-Lymphoma

We have assessed the potential use of the mononuclear cell (MNC) content as the sole assessment of graft quality in 35 patients receiving BEAM (carmustine, etoposide, cytosine arabinoside, melphalan) chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation for malignant lymphoma. PBPCs were mobilized with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), and each patient underwent two (n = 20) or three (n = 15) apheresis procedures. Median cell yields were 5.08 x 10(8) MNC/kg (range 1.59-15.70 x 10(8)) and 73.10 x 10(4) CFU-GM/kg (range 0.09-346.72 x 10(4)). All patients achieved hematologic recovery. Median days to neutrophils > or = 0.1 x 10(9)/L, neutrophils > or = 0.5 x 10(9)/L, and platelets > or = 25 x 10(9)/L were 11 (range 8-15), 13 (range 10-37), and 11 (range 7-41), respectively. A close correlation was observed between the MNC and CFU-GM dose (r = 0.79, p < 0.0001). We have previously defined a minimum threshold CFU-GM dose of 20 x 10(4)/kg for patients undergoing high-dose therapy. This corresponds with an MNC dose of 3 x 10(8)/kg. Comparison of engraftment in patients receiving 3 x 10(8) MNC/kg with those receiving lower doses demonstrated significantly longer times to recovery of neutrophils to > or = 0.5 x 10(9)/L and platelets to > or = 25 x 10(9)/L. All patients receiving an MNC dose of > or = 3 x 10(8)/kg achieved neutrophil and platelet recovery by days 12 and 24, respectively. These preliminary data demonstrate that for patients with lymphoma undergoing PBPC mobilization according to this protocol and treatment with BEAM chemotherapy, assessment of MNC dose alone is sufficient to predict early hematologic recovery. Additional assays such as CFU-GM or CD34+ cell counts may not be necessary if this MNC dose is reinfused.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Graft Survival; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leukapheresis; Leukocyte Count; Leukocytes, Mononuclear; Lymphoma; Lymphoma, Non-Hodgkin; Macrophages; Male; Melphalan

A prospective study was conducted to assess the efficacy and toxicity of a salvage regimen consisting of CCNU, Melphalan, and VP-16 (CAV) given at 28-day intervals in patients with Hodgkin's disease (HD) relapsing after primary therapy or refractory to the alternating MOPP/ABVD regimen.. This study included 58 patients (median age: 34 years), with resistant or relapsing HD. Primary therapy had consisted of alternating MOPP/ABVD (81%) or MOPP alone (19%); 38% of patients were relapsing from prior complete remission (CR) while 62% had resistant disease. Extranodal disease was present in 55% and B-symptoms in 72% of patients; one-fifth had bulky disease and/or bone marrow involvement. The CAV was used as first salvage in half of the patients.. Complete remission was obtained in 17 patients (29%); unfavorable factors for CR in univariate analysis were the presence of bulky disease and the failure to achieve CR with prior therapy. Nine patients (53% of remitters) have subsequently relapsed with a 10-month median duration of CR. The 3-year overall survival after CAV was 25% with an 18-month median survival; significant differences in survival were found according to the extent of disease, the presence of B-symptoms and the HD status (prior sensitive or resistant disease, first or subsequent relapse). Seven patients are long-term remitters (12%), and one of them has been given high-dose chemotherapy and autologous bone marrow transplantation at relapse after CAV. The CAV toxicity was mostly hematological; severe pancytopenia occurred in six cases with two cases of fatal infections and one of fatal hemorrhage.. CAV therapy was moderately effective as third-line salvage in patients with HD resistant to alternating MOPP/ABVD or previously given two different regimens for relapse; the toxicity was mostly hematological and supportive therapy was needed in one-third of the patients.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Doxorubicin; Drug Resistance; Etoposide; Female; Hodgkin Disease; Humans; Lomustine; Male; Mechlorethamine; Melphalan; Middle Aged; Pancytopenia; Prednisone; Procarbazine; Prospective Studies; Recurrence; Remission Induction; Salvage Therapy; Survival Rate; Vinblastine; Vincristine

In the present paper, we report two cases of normal pregnancy after high dose chemotherapy and autologous stem cell transplantation (ASCT) in two of the 72 women belonging to a group of 188 patients transplanted in our unit for advanced malignant lymphoma. These pregnancies occurred 19 and 33 months after high dose therapy in two women aged 27 and 28, neither of whom had received previous total body irradiation or pelvic radiotherapy. There are several reasons for the relatively low frequency of pregnancies after ASCT. In particular, the median age of the patients is 35 years, most of these women are transplanted in relapse and have received previous pretreatment with alkylating agents and the disease free survival rate does not exceed 40%. The preservation of long term fertility should be taken into account when deciding therapeutic options for young women with curable disease.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Infant, Newborn; Lymphoma, Large B-Cell, Diffuse; Mechlorethamine; Melphalan; Podophyllotoxin; Prednisone; Pregnancy; Pregnancy Outcome; Procarbazine; Remission Induction; Salvage Therapy; Vincristine

A simplified schedule of high-dose chemotherapy (HDC) consisting of melphalan (140 mg m-2) plus VP16 (2.5 g m-2) given over 12-18 h together with autologous non-cryopreserved autologous bone marrow transplant (ABMT) was used for treatment of relapsed (37 patients) and refractory (seven patients) patients and as first-line treatment (four patients) for poor-prognosis Hodgkin's disease. Two patients had a second HDC-ABMT after relapse following prior HDC-ABMT, giving a total of 50 procedures among 48 patients. The haematological recovery rate was 98% with a complete response rate of the Hodgkin's disease of > 90%. Factors significantly influencing response rate were performance status and the presence of liver involvement. Thirty-nine patients are alive, with 37 in continuous complete remission. The median duration of survival and median duration of remission have not been reached at a median follow-up time of 45 months. Adverse prognostic factors for survival were disease status at the time of HDC-ABMT (refractory versus relapse, with primarily refractory patients showing significantly poor survival) and the presence of liver involvement. High-dose chemotherapy with short-duration chemotherapy and non-cryopreserved bone marrow is an effective and safe treatment modality for patients with relapsed and poor-prognosis Hodgkin's disease.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Combined Modality Therapy; Cryopreservation; Dose-Response Relationship, Drug; Drug Administration Schedule; Etoposide; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Prognosis

To assess results, complications, treatment techniques, and patterns of failure in patients with bulky mediastinal Hodgkin's disease treated with combined modality therapy.. Between 1980 and 1988, 48 patients with Hodgkin's disease who had large mediastinal masses were treated at Stanford University. All patients were staged with clinical studies which included computed tomographic scans of the chest and bipedal lymphograms. Initially, 10 patients underwent staging laparotomy and splenectomy, subsequently all patients were staged by clinical criteria alone. Mediastinal mass ratios ranged from .35 to .85 (mean .46). The majority of patients had at least one site of extralymphatic extension (E-lesion) within the chest. Combined modality therapy included MOPP (prednisone deleted after mediastinal irradiation) in 15, ABVD in 14, and PAVe in 19 patients. All patients received mantle irradiation (mean dose 44 Gy) but only patients with abdominal disease received subdiaphragmatic irradiation.. The actuarial survival and freedom from relapse were 84% and 88% at 9 years. There was an intrathoracic component of failure in all seven patients who either failed to achieve an initial complete response or who experienced a relapse after a complete response. Both patients who experienced a relapse after a complete response achieved durable second responses with subsequent chemotherapy. Two of five patients who failed to achieve an initial complete response were treated successfully with alternative chemotherapy.. Routine combined modality therapy is the treatment of choice for patients with Hodgkin's disease who have large mediastinal masses.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; Male; Mechlorethamine; Mediastinal Neoplasms; Melphalan; Middle Aged; Prednisone; Procarbazine; Radiotherapy; Radiotherapy Dosage; Survival Rate; Vinblastine; Vincristine

Currently no treatment has proved successful in inducing ovarian steroidogenic and/or gametogenic recovery in patients with haematological malignancies treated by cytotoxic chemotherapy once biochemical failure becomes manifest i.e., when FSH levels exceed 40 IU/L. This paper reports two such cases with classical biochemical ovarian failure in which ovarian function was induced by brief stimulation with Human Menopausal Gonadotrophin (HMG).

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Carmustine; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Female; Follicle Stimulating Hormone; Hodgkin Disease; Humans; Leukemia, Myelomonocytic, Acute; Luteinizing Hormone; Melphalan; Menotropins; Ovulation Induction; Podophyllotoxin; Prednisone; Pregnancy; Pregnancy, Multiple; Primary Ovarian Insufficiency; Remission Induction; Teniposide; Thioguanine; Vincristine

Fifty-one consecutive patients with Hodgkin's disease (HD) have been treated with high-dose chemotherapy (HDT) and transplantation of autologous bone marrow (BM) (n = 44), autologous BM plus peripheral blood stem cells (PBSC) (n = 2), PBSC (n = 1), syngeneic (n = 1), or allogeneic BM (n = 3). All patients had received standard salvage chemotherapy prior to HDT and were classified as sensitive (n = 33) or resistant (n = 17) to this treatment; one patient was in untreated relapse prior to BMT. The preparative regimens for patients receiving autologous BM and/or PBSC consisted of cyclophosphamide, VP 16, and BCNU (CVB) (n = 44) or BCNU, etoposide, ara-C, and melphalan (BEAM) (n = 3). The patients receiving allogeneic transplants were treated with the CVB regimen (n = 2) or busulfan (16 mg/kg body wt.) and cyclophosphamide (200 mg/kg body wt.). With a median follow-up of 12 months, overall survival for 44 patients grafted with autologous BM is 61% +/- 9%, progression-free survival for patients with sensitive disease is 44% +/- 11%; no patient with resistant relapse survived beyond 1 year post transplant. Two of three patients grafted with allogeneic BM still survive 15 and 24 months after BMT with Karnofsky performance scores of 70% and 100%, respectively. The main toxicity encountered with the CVB regimen was interstitial pneumonia (IP), seen in four of 15 patients (27%) receiving > or = 600 mg/m2 of BCNU. Three of these patients have died. The results show that HDT followed by hematopoietic stem cell rescue may effectively salvage an important fraction of patients with relapsed HD who respond to standard chemotherapy. The same approach is largely unsuccessful in patients with proven refractoriness to standard chemotherapy. Whether HDT followed by BMT or PBSC support is superior to intensive chemotherapy without stem cell support can be answered only by a prospectively randomized trial.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Survival Rate

To evaluate an intensive therapy regimen of high-dose etoposide and melphalan and autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; and to determine possible prognostic factors that predict for long-term disease-free survival (DFS).. Seventy-three patients with advanced Hodgkin's disease who had failed to achieve remission with front-line chemotherapy (n = 16) or who had relapsed (n = 57) were treated with high-dose etoposide 60 mg/kg and melphalan 160 mg/m2 and ABMT. Previous therapy included mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), or hybrid MOPP/ABV. All patients received pretransplant cytoreduction with conventional-dose salvage chemotherapy and 40 also received pretransplant extended-field radiation to areas of bulky nodal disease (> 5 cm).. Response to high-dose etoposide and melphalan was determined at 3 months post-ABMT. The complete response (CR) rate was 75% (95% confidence interval [CI], 64% to 84%), including 35 of 50 patients with measurable disease before ABMT (70%; 95% CI, 60% to 86%). There were three early deaths (septicemia) and four late deaths (three interstitial pneumonitis, one intracerebral hemorrhage). Actuarial DFS is 38.6% at 4 years. Multivariate regression analysis showed that disease status at the time of ABMT (no evidence of disease [NED], nonbulky residual disease [NBRD], or bulky disease) was the most important factor determining DFS: 68% of those transplanted with NED versus 26% for patients with NBRD and 0% for bulky disease (P = .0002, log-rank test). Relapse in a previous radiation field was the only other significant prognostic factor.. Etoposide and melphalan is an effective and well-tolerated intensive therapy regimen in advanced Hodgkin's disease. Patients in complete remission after conventional-dose salvage therapy transplanted with this regimen enjoy superior long-term DFS.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Etoposide; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Survival Rate

Thirty-eight patients with refractory or relapsed non-Hodgkin's lymphoma (19 patients) or Hodgkin's disease (19 patients) were treated with salvage therapy. The peripheral stem cell collection was performed during hematologic recovery after myeloablative chemotherapy. In eight patients with Hodgkin's disease the number of CFU-GM collected was less than 0.5 x 10(4)/kg and these patients were excluded for stem cell transplantation. In the remaining 30 patients, a median of 4 x 10(4) CFU-GM/kg was collected (range 0.8-100 x 10(4)/kg) by three leukaphereses in 25 patients and six to 11 leukaphereses in five patients. Conditioning regimens were CBV (eight), BEAM (six), BEAC (10) and cyclophosphamide + total body irradiation (TBI) (six). Without TBI, the mean time for reaching a granulocyte count greater than 0.5 x 10(9)/l was 18 days and for a platelet count greater than 50 x 10(9)/l was 19 days in 23 out of 24 patients. With TBI, in five patients the mean time for reaching a granulocyte count greater tahn 0.5 x 10(9)/l was 37 days and for a platelet count greater than 50 x 10(9)/l was greater than 100 days. Complications were minor. There was only one toxic death. The outcome in these patients was similar to that observed in patients who received autologous bone marrow transplantation for advanced lymphomas. In conclusion, we observed good hematologic recovery except when TBI was used in the conditioning regimen.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion, Autologous; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Etoposide; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leukapheresis; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Salvage Therapy; Whole-Body Irradiation

The results of high-dose chemotherapy with melphalan or melphalan (carmustine) etoposide for 66 consecutive patients with relapsed or resistant Hodgkin's disease are described. 55 patients were evaluable for response and 22% of these achieved complete remission and 59% partial remission. The actuarial survival at 2 years was 45% and the principal factors determining survival were the sensitivity of the disease to therapy given before high-dose chemotherapy and the type of treatment received. Intensive chemotherapy with autologous bone marrow transplantation can produce long-term survivors among patients for whom long-term survival would otherwise be improbable. However, this treatment remains toxic with an uncertain place in management.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Drug Administration Schedule; Etoposide; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Survival Rate; Transplantation, Autologous

High dose chemotherapy and autologous bone marrow transplantation (ABMT) is an effective form of salvage therapy in patients with relapsed or resistant Hodgkin's disease. Patients with large tumour masses at the time of ABMT have a poorer prognosis and we have therefore administered intermediate dose BCNU, etoposide, cytarabine and melphalan (mini-BEAM) prior to high dose therapy with the same agents (BEAM) and ABMT in such patients. In addition we have used the same strategy in patients with bone marrow infiltration at the time of relapse in an attempt to clear the bone marrow for transplant. A total of 23 patients received mini-BEAM and 21 proceeded to BEAM and ABMT. Platelet engraftment was delayed compared to BEAM recipients who had not received mini-BEAM (P = 0.008) but there was only one procedure related death. Responses to BEAM and ABMT were not predicted by the response to mini-BEAM indicating a dose response effect at the upper end of the dose intensity spectrum. At 2 years, the overall survival and progression free survival are 61% and 46% respectively for this group of Hodgkin's patients with extremely poor prognosis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cytarabine; Etoposide; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Risk Factors; Time Factors

Optimum methods of harvesting circulating hematopoietic progenitors for autologous transplantation to support myeloablative cancer therapy are still uncertain, mostly because of the lack of an assay for marrow-repopulating stem cells. The CFU-GM assay, the commonly used indirect indicator of the quality of the graft, is poorly standardized and provides results evaluable only retrospectively. Based on the knowledge that hematopoietic progenitors express CD34 and CD33 differentiation antigens, we developed a dual-color direct immunofluorescence flow cytometry assay with the aim of replacing the CFU-GM assay advantageously. For this purpose, we applied both assays to 157 blood samples obtained daily throughout 20 different recoveries from pancytopenia induced by high-dose cyclophosphamide or etoposide cancer therapy with or without recombinant human GM colony-stimulating factor (rhGM-CSF). The appearance of CD34+ cells in the circulation indicated that hematopoietic progenitors had increased to more than 500 CFU-GM/mL, a level clinically adequate for large-scale harvest by leukapheresis. Total CD34+ cells correlated well with CFU-GM (r = .89), and data could be fitted by a linear regression line described by the equation y = 388.3 + 64.0x, where y = CFU-GM/mL and x = CD34+ cells per microliter. Moreover, in a series of six patients treated with myeloablative chemoradiotherapy, early hematopoietic recovery of marrow functions was predicted more accurately by the number of transplanted CD34+/CD33+ cells than by either total nucleated cells, CFU-GM, CD34+/CD33- cells, or CD34-/CD33+ cells. Data presented in this article favor clinical use of the CD34/CD33 flow cytometry assay to guide harvesting of circulating hematopoietic progenitors for autologous transplantation and contribute to better understanding of the role played by circulating hematopoietic progenitor cell subsets in marrow recovery after myeloablative cancer therapy.

Topics: Antigens, CD; Antigens, CD34; Antigens, Differentiation; Antigens, Differentiation, Myelomonocytic; Cell Separation; Colony-Forming Units Assay; Flow Cytometry; Fluorescent Antibody Technique; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Leukapheresis; Leukocyte Count; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Regression Analysis; Sialic Acid Binding Ig-like Lectin 3; Transplantation, Autologous

Although effective in achieving durable remission in selected tumors incurable by conventional-dose chemotherapy, high-dose regimens requiring bone marrow transplantation remain too toxic for widespread use. With the aim to improve the therapeutic index of high-dose therapy, we have developed a novel program whereby several non-cross-resistant agents (including total body irradiation at myeloablative dose) were delivered sequentially rather than concurrently. The regimen has been tested in 25 patients with Hodgkin's disease refractory to primary chemotherapy (MOPP and ABVD) or relapsed within 12 months after first complete remission. The efficacy of the sequential regimen (72% complete response rate, 49% event-free survival and freedom from progression at four years, with a median observation of 3.5 years for patients remaining alive) compares favorably with the activity so far reported for the most effective high-dose regimens. Toxicity was low; no toxic deaths occurred and only three life-threatening adverse events were documented after autografting. The excellent tolerability of the final myeloablative course most likely reflects the speed and completeness of haematologic recovery that followed the use of peripheral blood progenitors as the sole or additional source of myeloid stem cells. The reduction of haematologic toxicity was further emphasized when rhG-CSF was employed to both shorten post-chemotherapy neutropenic intervals and to collect large amounts of peripheral blood stem cells. We expect that the use of growth factors will have a major impact on the therapeutic index of high-dose regimens. This, in turn, will confirm their safety as primary treatment in selected high-risk subsets.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Male; Melphalan; Methotrexate; Prognosis; Recombinant Proteins; Remission Induction; Survival Rate; Transplantation, Autologous; Vincristine; Whole-Body Irradiation

Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: a) cyclophosphamide (7 g/m2); b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); c) total body irradiation (TBI; 12.5 gy, 5 fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Italy; Lung; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Prospective Studies; Pulmonary Gas Exchange; Total Lung Capacity; Transplantation, Autologous; Whole-Body Irradiation

The technique of total body irradiation (TBI) developed at Istituto Nazionale Tumori, Milan, Italy, is described. This technique consists of i) administration of 12.5 Gy and 14.85 Gy TBI for autologous and allogeneic bone marrow transplantation respectively; ii) in all cases in vivo dosimetry of absorbed TBI dose; and iii) radiation doses to lungs higher than previously described. As of June 1988, seventeen patients with Hodgkin's disease and four with lymphoblastic lymphoma received TBI and 120-180 mg/m2 melphalan. Respiratory function was prospectively evaluated demonstrating moderate and transient reduction of pulmonary function.

Topics: Adolescent; Adult; Bone Marrow Transplantation; Child; Combined Modality Therapy; Hodgkin Disease; Humans; Italy; Melphalan; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiotherapy Dosage; Whole-Body Irradiation

Based on observations that bulky disease at autologous bone marrow transplantation (ABMT) may be correlated with poor outcome in Hodgkin's disease, we have assessed the ability of conventional-dose chemoradiotherapy to reduce tumour burden to a minimum prior to ABMT. Thirty-seven patients with relapsed or refractory Hodgkin's disease referred for intensive therapy and ABMT were treated initially with one to five cycles of DHAP chemotherapy. All patients had previously received MOPP and ABVD chemotherapy or similar regimens. Four patients achieved complete remission (CR) and 12 partial remission (PR), for a total response rate of 43%. Eight partial responders and four non-responders to DHAP achieved significant further tumour reduction with local radiotherapy (five CR, seven PR). Six of 10 non-responders to DHAP responded to alternative salvage chemotherapy (mini-BEAM, CEP or augmented CVP). Overall, 24/37 patients (65%) achieved effective cytoreduction (nine CR, 15 PR with minimal disease) and have proceeded to ABMT. Patients with bulky disease at relapse or limited stage (II, IIIA) at diagnosis were less likely to respond to DHAP, but some of these could be cytoreduced with alternative therapy. In addition, the number of prior chemotherapy regimens correlated inversely with likelihood of response to DHAP. The results indicate that approximately two-thirds of patients with Hodgkin's disease who relapse after MOPP and ABVD-like regimens can achieve effective cytoreduction with conventional-dose chemoradiotherapy and proceed to ABMT in CR or PR with minimal disease.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Chi-Square Distribution; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Epirubicin; Etoposide; Evaluation Studies as Topic; Hodgkin Disease; Humans; Male; Melphalan; Prednisone; Premedication; Remission Induction; Vincristine

Between October 10, 1981 and December 31, 1987, we used the Hodgkin POF 81/12 protocol to treat 235 patients aged from 5 to 65 years (mean 30 years) with localized Hodgkin's disease clinically classified as stage IA (n = 6), stage IIA (n = 128) and stage IIB (n = 53). A contiguous lesion was present in 22 cases and a mediastinal lesion in 170 cases. The patients received 3 monthly courses of ABVD-MP (doxorubicin 25, bleomycin 10, vinblastine 6, dacarbazine 375 and methylprednisolone 120 mg per sq.m intravenously on days 1 and 15), except for stage IA non-mediastinal patients who received only one course. Thereafter, in the absence of failure (lack of changes or progression under chemotherapy), a 40 Gy wide focal irradiation and a 30 Gy prophylactic lumbo-splenic irradiation were performed. Complete remission (CR) was obtained in 229 patients, and the 6 failures (4 after ABVD-MP, 2 after radiotherapy) were treated with specific programmes. On December 1, 1988 (median survival 42 months, range 12-86 months) we had recorded 9 relapses (after 9 to 51 months) and 7 deaths (2 failures, 2 relapses and 3 patients in CR: ovarian carcinoma, road accident, exploratory pleural puncture). The current actuarial relapse and survival rates at 7 years are 5 and 94 respectively. Two unfavourable forms of the disease were identified: infra-diaphragmatic with massive lumbo-aortic lesions (5 cases: 1 failure, 1 relapse) and supra-diaphragmatic with a mediastinum/chest ratio of 0,45 or more (30 cases: 5 failures, 5 relapses). In the 200 patients devoid of these 2 risk factors the results obtained were: CR 100 percent, only 2 relapses and survival at 7 years 98 percent.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Child, Preschool; Dacarbazine; Doxorubicin; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Prednisone; Radiation Dosage; Vinblastine; Vincristine

Thirty-eight patients with previously treated Hodgkin's disease were given high dose combination chemotherapy using melphalan and BCNU and autologous bone marrow transplantation. In 25 patients etoposide was added in conventional dosage. During the course of the study the dose of melphalan was increased from 80 to 140 mg m-2 and the dose of BCNU from 300 to 600 mg m-2. The response rate was 76% with 53% complete remission. Forty-five per cent of the patients are free of disease at 4-20 months follow-up. There were eight (26%) treatment-related deaths due to lung damage (seven cases) and irreversible cardiac failure (one case). Fatal lung damage occurred only in patients receiving 600 mg m-2 of BCNU with high dose melphalan. The dose of BCNU given with high dose melphalan should not exceed 500 mg m-2. This treatment is effective against relapsed Hodgkin's disease but must be used cautiously. The best time for its use remains to be determined.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Etoposide; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged

Twenty patients with Hodgkin's disease which had relapsed at least once after chemotherapy, were treated with melphalan 140-220 mg/m2 i.v. followed by reinfusion of non-cryopreserved autologous bone marrow. Four patients (20%) remain alive and disease-free 28, 45, 52, and 96 months after treatment respectively. There were no treatment-related deaths. This appears to be the only reported series of patients treated with a single agent in this situation. The results are comparable to those achieved by multi-agent regimens with autologous or allogeneic bone marrow transplantation.

Topics: Adult; Bone Marrow Transplantation; Cell Survival; Dose-Response Relationship, Drug; Female; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Transplantation, Autologous

Topics: Antineoplastic Agents; Chlorambucil; Hodgkin Disease; Humans; Leukemia; Melphalan; Neoplasms; Risk Factors

Seventeen patients with advanced lymphoma were treated with high-dose chemotherapy with autologous bone marrow rescue. In 11 patients with non-Hodgkin's lymphoma (NHL) there were 2 complete remissions (CRs) and 2 partial remissions (PRs), and in 6 patients with Hodgkin's disease there were 5 CRs. Three patients remain well in unmaintained remission (days 874, 446 and 351), and a further 2 are alive and still receiving treatment (days 650 and 558). This type of therapy appears useful and should now be considered earlier in the course of the disease.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cyclophosphamide; Cytarabine; Female; Hodgkin Disease; Humans; Lymphoma; Male; Melphalan; Methotrexate; Middle Aged; Podophyllotoxin

Topics: Bone Marrow Transplantation; Combined Modality Therapy; Hodgkin Disease; Humans; Melphalan

Experience with 19 autologous bone marrow transplantations shows that this approach may produce a high proportion of complete remissions in otherwise resistant tumours. Although most responses are of short duration, they suggest that longterm disease-free survival may be achieved in patients with poor prognosis if treated earlier in the course of disease.

Topics: Adult; Bone Marrow Transplantation; Child; Cyclophosphamide; Female; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Male; Melphalan; Middle Aged; Postoperative Complications; Remission Induction

Vindesine (desacetyl vinblastine amide sulfate, DVA) was used in combination with CCNU (lomustine) and melphalan (Alkeran) (CAD) to treat 15 heavily pretreated patients with Hodgkin's disease in relapse. The patients were treated with up to six cycles, depending upon their response. Two patients (13%) achieved a complete remission (CR) and five (33%) patients a partial remission (PR). The major toxicity was prolonged thrombocytopenia, which was decreased by a reduction in the initial drug doses for patients who had received extensive prior chemotherapy and radiotherapy (RT). The CAD regimen was then alternated with nitrogen mustard or cyclophosphamide, vincristine, procarbazine, and prednisone (MOPP, C-MOPP) and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV) for a total of nine cycles in 25 patients with Hodgkin's disease in relapse with somewhat more favorable prognostic features. Two patients also received low-dose RT to areas of bulky nodal disease. Eleven patients (44%) achieved a CR and seven (28%) a PR. Of the 11 CR patients, six remain in remission. The serious toxicity was comparable to that seen with other combination chemotherapy regimens. These results indicated that the CAD/MOPP/ABVD regimen is as active as other so-called 'salvage' regimens for Hodgkin's disease in relapse, and suggest that it might be useful for newly diagnosed Hodgkin's disease.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Doxorubicin; Female; Hodgkin Disease; Humans; Lomustine; Male; Mechlorethamine; Melphalan; Middle Aged; Prednisone; Procarbazine; Vinblastine; Vincristine; Vindesine

Topics: Asparaginase; Child; Cyclophosphamide; Cytosine; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Melphalan; Mercaptopurine; Methotrexate; Neoplasms; Nitrogen Mustard Compounds; Osteosarcoma; Prednisone; Procarbazine; Prognosis; Remission, Spontaneous; Rhabdomyosarcoma; Teniposide; Thioguanine; Vincristine; Wilms Tumor

Acute myelocytic leukemia occurring many years after intensive radiotherapy and/or chemotherapy has been reported in 82 patients with Hodgkin's disease, 58 patients with multiple myeloma, and 40 patients with chronic lymphocytic leukemia. The precise incidence of this occurrence is uncertain, since the total number of patients at risk is unknown. Most patients with Hodgkin's disease had received intensive radiation therapy. Many also received chemotherapy. One-third of the patients with myeloma were treated only with melphalan. Acute leukemia may occur as part of the natural history of Hodgkin's disease and multiple myeloma; it has been seen with increasing frequency in recent years due to improved survival secondary to better treatment. It is also possible that radiotherapy and/or chemotherapy may be causally related to the development of acute leukemia.

Topics: Antineoplastic Agents; Hodgkin Disease; Humans; Leukemia, Lymphoid; Melphalan; Multiple Myeloma; Neoplasms; Radiotherapy

Topics: Adenine Nucleotides; Adenosine Diphosphate; Amidines; Antibiotics, Antineoplastic; Bleomycin; Blood Platelets; Breast Neoplasms; Bronchial Neoplasms; Cyclophosphamide; Doxorubicin; Firefly Luciferin; Fluorouracil; Glyoxal; Hodgkin Disease; Humans; Hydrazones; Leukemia; Luciferases; Lymphocytes; Melphalan; Methotrexate; Neoplasms; Nephelometry and Turbidimetry; Plasmacytoma; Platelet Aggregation; Vinca Alkaloids

Topics: Animals; Antineoplastic Agents; Biological Assay; Carmustine; Cyclohexanes; Cyclophosphamide; Cytarabine; Daunorubicin; Disease Models, Animal; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Fluorouracil; Hodgkin Disease; Humans; Leukemia; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Male; Mechlorethamine; Melphalan; Mice; Mice, Inbred AKR; Multiple Myeloma; Nitrosourea Compounds; Prednisone; Remission, Spontaneous; Vinblastine; Vincristine

Topics: Adult; Antineoplastic Agents; Bence Jones Protein; Hodgkin Disease; Humans; Immunoglobulin D; Male; Melphalan; Plasma Cells; Plasmacytoma; Radiotherapy; Skin Neoplasms; Testicular Neoplasms

Topics: Agammaglobulinemia; Antibodies; Antigens, Bacterial; Blood Protein Disorders; Blood Proteins; Busulfan; Chlorambucil; Electrophoresis, Paper; Hodgkin Disease; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulins; Immunosuppression Therapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mannomustine; Melphalan; Primary Myelofibrosis; Radiation Effects; Saliva; Skin Tests; Spleen; Time Factors

Topics: Adolescent; Aged; Bone Neoplasms; Female; Hemangiosarcoma; Hodgkin Disease; Humans; Leukopenia; Lymphoma, Large B-Cell, Diffuse; Male; Melanoma; Melphalan; Neoplasms; Ovarian Neoplasms; Sarcoma, Ewing; Testicular Neoplasms; Thrombocytopenia; Tonsillar Neoplasms; Uterine Neoplasms

Topics: Adenocarcinoma; Antineoplastic Agents; Chlorambucil; Colchicine; Culture Techniques; Cyclophosphamide; Dactinomycin; Female; Floxuridine; Fluorouracil; Hodgkin Disease; Humans; Melphalan; Mercaptopurine; Methotrexate; Nandrolone; Neoplasms; Nitrogen Mustard Compounds; Norethindrone; Prednisolone; Progesterone; Testosterone; Thiotepa; Uterine Neoplasms; Vinblastine

Topics: Antimetabolites; Antineoplastic Agents; Breast Neoplasms; Carcinoma; Chlorambucil; Choriocarcinoma; Cyclophosphamide; Female; Fluorouracil; Hodgkin Disease; Humans; Hydrazines; Intestinal Neoplasms; Melphalan; Methotrexate; Multiple Myeloma; Ovarian Neoplasms; Pregnancy; Thiotepa; Vinblastine

Topics: Adult; Antineoplastic Agents; Busulfan; Chlorambucil; Hodgkin Disease; Humans; Leukemia; Lymphoma; Male; Mechlorethamine; Melphalan; Vinblastine

Topics: Adenocarcinoma; Aged; Breast Neoplasms; Colonic Neoplasms; Cyclophosphamide; Female; Hodgkin Disease; Humans; Intestinal Neoplasms; Liver Neoplasms; Male; Melphalan; Middle Aged; Neoplasms; Palliative Care; Stomach Neoplasms; Thiotepa

Topics: Adult; Alkylating Agents; Antimetabolites; Antineoplastic Agents; Dactinomycin; Female; Fluorouracil; Hodgkin Disease; Humans; Lung Neoplasms; Male; Melphalan; Methotrexate; Middle Aged; Neoplasms; Phytotherapy; Plants, Medicinal; Plants, Toxic; Podophyllum; Radiography; Sarcoma, Ewing; Thiotepa; Vincristine

Topics: Breast Neoplasms; Carcinoma, Bronchogenic; Dysgerminoma; Female; Gastrointestinal Neoplasms; Hodgkin Disease; Humans; Liver Neoplasms; Lymphoma; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melanoma; Melphalan; Multiple Myeloma; Neoplasms; Ovarian Neoplasms; Sarcoma

Topics: Abdomen; Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Colonic Neoplasms; Cyclophosphamide; Female; Geriatrics; Hodgkin Disease; Humans; Hypothermia; Hypothermia, Induced; Leiomyosarcoma; Mechlorethamine; Melanoma; Melphalan; Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Pelvis; Rectal Neoplasms; Retroperitoneal Neoplasms; Uterine Cervical Neoplasms; Vaginal Neoplasms

Topics: Geriatrics; Hodgkin Disease; Iatrogenic Disease; Leukopenia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Neoplasms; Radiography, Thoracic; Sarcoma; Thrombocytopenia; Toxicology

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Drug Therapy; Hodgkin Disease; Lymphatic System; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mannomustine; Melphalan; Neoplasms; Piperazines; Sarcoma

Topics: Chlorambucil; Cyclophosphamide; Genetic Diseases, X-Linked; Hodgkin Disease; Humans; Leukemia, Hairy Cell; Lymphatic Diseases; Melphalan; Nitrogen Mustard Compounds; Peptide Nucleic Acids; Prednisolone; Prednisone; Severe Combined Immunodeficiency; Thiotepa

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antineoplastic Agents; Aziridines; Bone Marrow Transplantation; Colchicine; Cyclophosphamide; Dactinomycin; Hodgkin Disease; Mechlorethamine; Melphalan; Neoplasms; Radioisotopes; Radiotherapy, High-Energy; Triethylenemelamine; Vinblastine

Topics: Adolescent; Child; Geriatrics; Head and Neck Neoplasms; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mandibular Neoplasms; Maxillary Neoplasms; Melanoma; Melphalan; Multiple Myeloma; Neoplasms; Orbital Neoplasms; Plasmacytoma; Sarcoma; Sarcoma, Kaposi

Topics: Antineoplastic Agents; Aziridines; Breast Neoplasms; Cell Nucleus; Coloring Agents; Cyclophosphamide; Female; Hodgkin Disease; Humans; Hyperplasia; Hypertrophy; Mathematics; Melphalan; Ovarian Neoplasms; Pathology; Staining and Labeling; Thiotepa; Triethylenemelamine; Uterine Neoplasms; Vaginal Smears

Topics: Hodgkin Disease; Humans; Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mechlorethamine; Melphalan; Multiple Myeloma; Nitrogen Mustard Compounds; Phenylalanine; Plasma Cells; Sarcoma