melphalan and Lymphoma--B-Cell

Patients suffering from refractory aggressive B-cell lymphoma not responding to salvage chemotherapy have a dismal prognosis. CAR T-cells or allogeneic stem cell transplantation (SCT) are potentially curative approaches. However, obtaining a remission, and lowering tumor burden before consolidation seems crucial for long-term efficacy of both treatment modalities.. In this retrospective analysis, we reviewed patients with chemoresistant aggressive B-cell lymphoma, defined as being refractory or progressive to at least second line salvage chemotherapy including the regimen immediately preceding autologous stem cell transplantation (ASCT), treated at 2 tertiary centers, who were eligible for intensive treatment using single agent high-dose (HD) melphalan to obtain a remission before consolidating therapy.. We identified 36 patients that received single agent HD melphalan and ASCT as remission induction followed by CAR T-cells or allogeneic stem cell transplantation (SCT). Thirteen of the evaluable patients (39.4%) achieved a partial remission and 9 patients (27.73%) a complete remission, resulting in an overall response rate (ORR) of 66.7%. High remission rates were seen across all subgroups including patients with primary refractory lymphoma (ORR 58.3%), uncontrolled disease and high tumor burden as indicated by increased LDH levels (ORR 66.7% for patients with elevated LDH above 2 times upper limit of norm). 22 patients proceeded to allogeneic SCT and 5 to CAR T-cell therapy. Treatment related mortality of ASCT was 5.5% (2 patients, both due to infections). Two-year overall survival of all patients was 15.8%, primarily due to a high non-relapse mortality (45.5%) of allogeneic SCT patients treated with myeloablative conditioning chemotherapy.. Single agent HD melphalan produces high remission rates in patients with chemoresistant, uncontrolled aggressive B-cell lymphoma and provides a window of opportunity for consolidation therapy.. Patient with refractory/relapsed aggressive B-cell lymphoma after salvage therapy are an unmet medical need because of their very poor prognosis. In our retrospective analysis of 36 patients we showed that single agent high-dose melphalan can achieve high response rates (ORR 66.7%) even in uncontrolled disease enabling consolidation therapy e.g. with allogeneic stem cell transplantation or CAR T-cell therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Consolidation Chemotherapy; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma; Lymphoma, B-Cell; Melphalan; Neoplasm Recurrence, Local; Retrospective Studies; Salvage Therapy; Stem Cell Transplantation; Transplantation, Autologous

Growing understanding of the important role of B lymphocytes in alloreactivity has paved the way for evaluating anti-B cell therapy with rituximab in patients undergoing allogeneic hematopoietic cell transplantation. Data suggesting a beneficial reduction in incidence and severity of acute graft-versus-host disease (GVHD) are limited to non-randomized studies from single institutions using higher than conventional doses of rituximab. Additionally, rituximab is used as an effective treatment of corticosteroid-refractory chronic GVHD with good responses, particularly in cases of dermatologic and mucosal involvement. Post-transplant administration of rituximab appears to reduce the rate of chronic GVHD in preliminary studies.

Topics: Adrenal Cortex Hormones; Adult; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Clinical Trials as Topic; Drug Administration Routes; Drug Administration Schedule; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, B-Cell; Melphalan; Middle Aged; Procarbazine; Rituximab; Transplantation Conditioning; Transplantation, Homologous; Vinblastine

A few prospective trials in HIV-positive patients with Burkitt lymphoma (BL) or high-grade B-cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicentre phase II trial addressing a new dose-dense, short-term therapy aimed at maintaining efficacy and improving tolerability. The experimental programme included a 36-day polychemotherapy induction followed by high-dose cytarabine-based consolidation and response-tailored BEAM (carmustine, etoposide, cyatarabine, and melphalan)- conditioned autologous stem cell transplantation (ASCT). This therapy would be considered active if ≥11 complete remissions (CR) after induction (primary endpoint) were recorded among 20 assessable patients. HIV-positive adults (median age 42, range 26-58; 16 males) with untreated BL (n = 16), HGBL (n = 3) or double-hit lymphoma (n = 1) were enrolled. All patients had high-risk features, with meningeal and bone marrow infiltration in five and nine patients respectively. The experimental programme was safe and active in a multicentre setting, with only two episodes of grade 4 non-haematological toxicity (hepatotoxicity and mucositis), and no cases of systemic fungal infections; two patients died of toxicity (bacterial infections). Response after induction (median duration: 47 days; interquartile range 41-54), was complete in 13 patients and partial in five [overall response rate = 90%; 95% confidence interval (CI) = 77-100]. All responders received consolidation, and five required autologous stem cell transplant. At a median follow-up of 55 (41-89) months, 14 patients are relapse-free and 15 are alive, with a five-year progression-free survival and an overall survival of 70% (95% CI = 60-80%) and 75% (95% CI = 66-84) respectively. No patient with cerebrospinal fluid (CSF)/meningeal lymphoma experienced central nervous system recurrence. With respect to previously reported regimens, this programme was delivered in a shorter period, and achieved the main goal of maintaining efficacy and improving tolerability.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Burkitt Lymphoma; Carmustine; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; HIV Infections; Humans; Lymphoma, B-Cell; Male; Melphalan; Middle Aged; Transplantation, Autologous

Chemo-refractory NHL has a very poor outcome; the addiction of RIT to salvage regiment pre ASCT had recently demonstrated promising results.We performed a retrospective sequential study to determine the feasibility of standard Zevalin with BEAM in high-risk relapse/refractory NHL. A matched cohort analysis with a group treated with standard BEAM without Zevalin was performed as secondary endpoint. Between October 2006 and January 2013, 37 NHL patients at high risk for progression or early (< 1 year) or multiple relapses were treated with Z-BEAM and ASCT after R-DHAP or R-ICE as salvage therapy. Clinical characteristics were 19 refractory and 18 early or multiple relapse; 16 patients received 1, and 21 had 2 or more previous rituximab-containing chemotherapy. At the end of treatment, response was CR 22 (59%), PR 10 (27%), PD 4 (11%), and toxic death (TD) 1 (3%). With a median follow up of 61 months, 3-year PFS was 61% and OS 61%. Fifteen patients died, 12 of lymphoma. Comparison with 21 treated with BEAM alone showed a numerical higher 3-yr PFS rate in favor of Z-BEAM but not statistically significant (57 vs 48%). With the limitation of the small sample subgroup analysis, a significant benefit was observed in relapsed patients for PFS (78% Z-BEAM vs 22% BEAM p = 0.016) and OS (83% Z-BEAM vs 22% BEAM p = 0.001). In relapsed/refractory high-risk NHL, Z-BEAM+ASCT is able to achieve a good ORR. Three-year PFS is promising for early relapsed patients but is not satisfactory for those with refractory disease.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Drug Resistance, Neoplasm; Female; Hematopoietic Stem Cell Transplantation; Humans; Italy; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Invasiveness; Podophyllotoxin; Recurrence; Retrospective Studies; Salvage Therapy; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult; Yttrium Radioisotopes

Salvage therapy followed by high-dose therapy (HDT) remains a mainstay for patients with relapsed lymphoma, however no optimal regimen has been defined. Here we report on the results of R-DexaBEAM (rituximab, dexamethasone, carmustine, etoposide, cytarabine, melphalan) followed by HDT. Patients aged 18-65 years, Eastern Cooperative Oncology Group performance score 0-2, with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) were eligible. R-Dexa-BEAM was given for two cycles followed by stem cell mobilization and HDT. Primary endpoint of the trial was progression-free-survival (PFS). One hundred and three patients were included: aggressive NHL (aNHL): diffuse large B-cell lymphoma 55, mantle cell lymphoma 7, follicular lymphoma (FL) grade 3: 5, indolent Lymphoma (iNHL): FL grade 1-2: 29, marginal zone lymphoma 6, Immunocytoma 1. The overall response rate after salvage therapy was 62% for aNHL and 78% for iNHL patients. 66% of patients with aNHL and 86% with iNHL underwent HDT. Treatment-related mortality for HDT was 1·3%. For aNHL patients, the median PFS was 0·83 years with 44% alive at the median follow-up of 7·3 years. Corresponding figures for iNHL were: median PFS 3·7 years and 72% alive after 8 years. The combination of rituximab with DexaBEAM followed by HDT resulted in high response rates and sustained remissions in responders. R-DexaBEAM followed by HDT can be considered a valid salvage option for NHL.

Topics: Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Dexamethasone; Dose-Response Relationship, Drug; Drug Administration Schedule; Etoposide; Female; Hematopoietic Stem Cell Mobilization; Humans; Kaplan-Meier Estimate; Lymphoma, B-Cell; Male; Melphalan; Middle Aged; Patient Selection; Prospective Studies; Recurrence; Remission Induction; Rituximab; Salvage Therapy; Young Adult

A phase II trial evaluated safety, feasibility and efficacy of a sequential tandem approach combining myeloablative BEAM chemotherapy and autologous stem cell transplantation (ASCT) with myeloablative radioimmunotherapy (HD-RIT), with (131)I-anti-CD20 antibody ((131)I-rituximab), followed by a second ASCT in patients with relapsed or refractory CD20+ B-cell lymphoma. According to protocol, 16 patients with relapsed (n = 14) and refractory (n = 2) CD20+ B-cell lymphoma received salvage therapy with rituximab and Dexa-BEAM, followed by BEAM (HD chemotherapy) and high-dose myeloablative radioimmunotherapy 2-6 months after BEAM. Nine of 16 patients received HD-RIT; seven patients were excluded before HD-RIT because of toxicity or progressive disease. Disease histologies were follicular lymphoma (FL) grades 1 and 2 (n = 4), transformed follicular (FL 3b; n = 6), diffuse large B-cell (DLBCL; n = 4), mantle cell (n = 1) and marginal zone lymphoma (n = 1). After a median follow-up of 50.4 months for OS and 39.7 months for progression-free survival (PFS), estimated 4-year OS and PFS were 67% and 64%, respectively. The estimated 4-year OS and PFS for patients with FL were 80% and 78%, respectively. Toxicity was significant, including one fatal outcome due to pneumonitis. Tandem transplants consisting of HD chemotherapy followed by HD-RIT with (131)I-coupled anti-CD20 are manageable and effective but toxic treatment modalities for relapsed poor prognosis CD20+ B-NHL.

Topics: Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Dexamethasone; Disease-Free Survival; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Etoposide; Humans; Iodine Radioisotopes; Kaplan-Meier Estimate; Lymphoma, B-Cell; Male; Melphalan; Middle Aged; Myeloablative Agonists; Prospective Studies; Radioimmunotherapy; Recurrence; Rituximab; Salvage Therapy; Stem Cell Transplantation

This study was designed to evaluate the safety and efficacy of a conventional dose of yttrium-90 ((90)Y) ibritumomab tiuxetan combined with the etoposide rabinoside acytarabine melphalan (BEAM) regimen before autologous stem cell transplantation (ASCT) in chemosensitive relapsed or refractory low-grade B-cell lymphomas.. From March 2005 to August 2006, 77 prospective patients were included, 69 (90%) with follicular lymphomas.. The last salvage chemotherapy regimen included rituximab for 74 patients and ASCT for 75 patients. Before ASCT, rates of complete response/unconfirmed response (CR/CRu) and partial response were 77% and 23%, respectively. After zevaline-BEAM (Z-BEAM), time to >1 × 10(9)/L neutrophils was 12 days (range, 9-35 days), and time to >20 × 10(9)/L platelets was 12 days (range, 3-42 days). No other significant extrahematologic toxicity was observed. Three months after ASCT, 68 patients (88%) were in CR/CRu. After a median follow-up of 28 months, 2-year event-free survival (EFS) and overall survival were 63% and 97%, respectively, but EFS for first-relapsed patients was 72%. When using patients as their own controls, 2-year EFS was superior after ASCT and compared favorably with the duration of response of last chemotherapy (62% vs. 37%, P = .007) (Point 1.10).. Z-BEAM appears safe and needs to be further evaluated in a randomized trial.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, B-Cell; Melphalan; Middle Aged; Neoplasm Staging; Podophyllotoxin; Rituximab; Survival Analysis; Transplantation, Autologous; Treatment Outcome; Young Adult

To determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 ((90)Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation.. Eligible patients had relapsed or refractory CD20+ non-Hodgkin's lymphoma (NHL). Individualized (90)Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of (90)Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation.. Forty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively.. Dose-escalated (90)Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.

Topics: Adult; Aged; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cytarabine; Female; Humans; Kaplan-Meier Estimate; Lymphoma, B-Cell; Male; Maximum Tolerated Dose; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Podophyllotoxin; Radioimmunotherapy; Radiotherapy Dosage; Salvage Therapy; Transplantation, Autologous

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 investigated the efficacy and safety of administering high-dose rituximab (HD-R) in combination with high-dose carmustine, cytarabine, etoposide, and melphalan chemotherapy and autologous stem-cell transplantation (SCT) in patients with recurrent B-cell aggressive non-Hodgkin's lymphoma (NHL).. Sixty-seven consecutive patients were treated. Rituximab was administered during stem-cell mobilization (1 day before chemotherapy at 375 mg/m(2) and 7 days after chemotherapy at 1,000 mg/m(2)), together with granulocyte colony-stimulating factor 10 mug/kg and granulocyte-macrophage colony-stimulating factor 250 microg/m(2) administered subcutaneously daily. HD-R of 1,000 mg/m(2) was administered again days 1 and 8 after transplantation. The results of this treatment were retrospectively compared with those of a historical control group receiving the same preparative regimen without rituximab.. With a median follow-up time for the study group of 20 months, the overall survival rate at 2-years was 80% (95% CI, 65% to 89%) for the study group and 53% (95% CI, 34% to 69%) for the control group (P = .002). Disease-free survival was 67% (95% CI, 51% to 79%) for the study group and 43% (95% CI, 26% to 60%) for the control group (P = .004). The median time to recovery of absolute neutrophil count to >/= 500 cells/microL was 11 days (range, 8 to 37 days) for the rituximab group and 10 days (range, 8 to 17 days) for the matched control group (P = .001). However, infections were not significantly increased in patients treated with rituximab.. The results of this study suggest that using HD-R and autologous SCT is a feasible and promising treatment for patients with B-cell aggressive NHL.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Disease-Free Survival; Etoposide; Female; Humans; Infusions, Intravenous; Injections, Subcutaneous; Lymphoma, B-Cell; Male; Melphalan; Middle Aged; Rituximab; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Autografts; Carmustine; Cytarabine; Humans; Lymphoma, B-Cell; Male; Melphalan; Podophyllotoxin; Renal Insufficiency; Severity of Illness Index; Stem Cell Transplantation; Transplantation Conditioning

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Female; Humans; Intraocular Lymphoma; Intravitreal Injections; Lymphoma, B-Cell; Male; Melphalan; Retinal Neoplasms; Tomography, Optical Coherence; Visual Acuity

Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours.. Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively.. The four patients with in-transit MCC had three complete responses (CR) and one partial response (PR); the two patients with SCC had one CR and one stable disease (SD); the patients with desmoid tumours had two PR and one SD. A CR was also observed for the patient with a giant cell tumour, but the patient with PVNS had a SD. The patient with cutaneous metastases of B-cell lymphoma showed a CR, however with rapid systemic progression. Local toxicity according to Wieberdink was grade II in 10 patients (83%) and grade III in two patients (17%).. These results show that ILP can be used as a treatment option also for more rare disease entities when other treatments have failed.

Topics: Abdominal Neoplasms; Adenomatous Polyposis Coli; Antineoplastic Agents, Alkylating; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Extremities; Fibromatosis, Aggressive; Giant Cell Tumors; Humans; Hyperthermia, Induced; Lymphoma, B-Cell; Melphalan; Perfusion; Rare Diseases; Synovitis, Pigmented Villonodular; Tumor Necrosis Factor-alpha

Eighty-eight dogs with relapsed lymphoma were treated with the MOMP (mechlorethamine, vincristine, melphalan and prednisone) protocol on a 28-day treatment cycle. The overall response rate (ORR) to the MOMP protocol was 51.1% for a median of 56 days (range 7-858 days). Twelve percent of dogs experienced a complete response for a median of 81 days (range 42-274 days) and 38.6% experienced a partial response for a median of 49 days (range 7-858 days). Dogs with T-cell lymphoma had an ORR of 55% for a median of 60 days (range 49-858 days) while those with B-cell lymphoma had an ORR of 57% for a median of 81 days (range 7-274 days) (P = 0.783). The overall survival time for all dogs was 183 days (range 17-974 days). Fifty-four percent of dogs experienced toxicity with the majority classified as grade I. The MOMP protocol seems well-tolerated and is an option for dogs with relapsed lymphoma.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Dog Diseases; Dogs; Female; Lymphoma; Lymphoma, B-Cell; Lymphoma, T-Cell; Male; Mechlorethamine; Melphalan; Prednisone; Recurrence; Survival Analysis; Vincristine

We have studied the feasibility and efficacy of intensified R-MegaCHOP-ESHAP-BEAM therapy in high-risk aggressive B-cell lymphomas. Altogether 105 patients (19-64 years) with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBL) or follicular lymphoma grade 3 (FL3) with an age-adjusted International Prognostic Index of 2-3 were recruited. Treatment consisted of three cycles of high-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), followed by three cycles of R-ESHAP (rituximab, etoposide, methylprednisolone, cytarabine, cisplatin) and high-dose consolidation with BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem cell transplant. The 5-year progression-free survival (PFS) was 72% (DLBCL 60%, PMBL 89%) and overall survival (OS) was 74% (DLBCL 61%, PMBL 89%) after a median follow-up of 85 months. However, an independent prognostic factor was age only, with patients ≤ 45 years having 5-year PFS 90% and patients > 45 years having PFS 54%. PMBL had better prognosis than DLBCL/FL3 in patients > 45 years (PFS, 88% vs. 48%), but not in younger patients (PFS, 91% vs. 94%).

Topics: Adult; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Consolidation Chemotherapy; Cyclophosphamide; Cytarabine; Disease Progression; Doxorubicin; Etoposide; Female; Humans; Induction Chemotherapy; Lymphoma, B-Cell; Male; Melphalan; Methylprednisolone; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Podophyllotoxin; Prednisone; Prognosis; Rituximab; Treatment Outcome; Vincristine; Young Adult

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, B-Cell; Melphalan; Radioimmunotherapy; Treatment Outcome; Yttrium Radioisotopes

Topics: Administration, Oral; Animals; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Disease Progression; Drug Therapy, Combination; Hematologic Diseases; Hematology; Humans; Lenalidomide; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Melphalan; Multiple Myeloma; Prednisone; Pyrazines; Quinolones; Recurrence; Stem Cell Transplantation; Thalidomide; Transplantation Conditioning; Transplantation, Autologous

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Drug Hypersensitivity; Female; Fibroblast Growth Factor 7; Foot Dermatoses; Hand Dermatoses; Humans; Lymphoma, B-Cell; Melphalan; Middle Aged; Mitogens; Podophyllotoxin

Recently, the standard treatments for hematological malignancies have shown dramatic improvement. For chronic myeloid leukemia, imatinib has become the treatment of choice in initial treatment, and its long-term effectiveness and safety have been confirmed. For acute myelogenous leukemia, cytarabine with anthracycline agent is believed to be the standard treatment in first remission induction therapy. To improve the efficacy of the first remission induction chemotherapy, the addition of gemutuzumab ozogamicin has been investigated intensively all over the world. However, there are many obstacles to conducting its clinical trial in Japan. The addition of rituximab to CHOP improves the survival of patients with diffuse large B-cell lymphoma. For follicular lymphoma patients, rituximab with conventional chemotherapies are considered the standard treatments, but the question of which conventional chemotherapy is better is unsolved. MP therapy had long been the standard treatment for elderly patients with multiple myeloma, but MP therapy plus thalidomide with MP therapy has been found to be superior. In patients who are candidates for autologous stem-cell transplantation, VAD therapy or high-dose dexamethasone therapy followed by autologous stem-cell transplantation is considered the treatment of choice. But the number of transplantations and the timing of second transplantation need more investigation. Considering the overall situation with regard to the standard treatments of hematological malignancies in Japan, there is little difference in practice from western countries. However, the framework of conducting clinical trials to investigate standard treatment in Japan is unsatisfactory.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Melphalan; Multiple Myeloma; Prednisone; Rituximab; Survival Rate; Vincristine

A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Disease-Free Survival; Etoposide; Feasibility Studies; Female; Humans; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Middle Aged; Mitoxantrone; Peripheral Blood Stem Cell Transplantation; Prospective Studies; Rituximab; Transplantation, Autologous; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cryoglobulins; Cytarabine; Humans; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Podophyllotoxin; Transplantation, Autologous

Previously, we have shown that patients with diffuse large B-cell lymphoma (DLBCL) transplanted with contaminated bone marrow (BM) generally have a poor outcome. Whether this is also the case when peripheral blood progenitor cell (PBPC) grafts are used is not known. Forty-three patients with chemosensitive DLBCL or follicular lymphoma grade 3 (FLgr3) were treated with high-dose therapy (HDT) and autologous stem cell support. Nine patients received purged grafts. Quantitative real-time polymerase chain reaction (QRT-PCR) for either the BCL2/IgH translocation or allele specific oligonucleotide (ASO) QRT-PCR for the immunoglobulin heavy chain (IgH) complementarity-determining region 3 were used. Nine of 25 (36%) PBPC grafts contained tumour cells as tested by QRT-PCR, including two grafts purged by CD34(+) cell enrichment combined with B-cell depletion. The level of contamination of the PBPC/CD34(+) cells ranged from 0 to 8.28%. No relationship could be shown between the total number of tumour cells infused and relapse. Patients receiving PCR-positive or PCR-negative PBPC grafts had similar progression-free survival (PFS) (P = 0.49). However, a significant difference was seen in PFS and overall survival (OS) for the patients given >/=6.1 x 10(6) CD34(+) cells/kg compared with those given <6.1 x 10(6) CD34(+) cells/kg (P = 0.01 and P < 0.05 respectively).

Topics: Adult; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Etoposide; Female; Graft Survival; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Middle Aged; Salvage Therapy; Treatment Outcome

From January 1st 1995 to March 31st 2003 a total of 51 autologous stem-cell transplantations (auto-HSCT) in 49 children with non Hodgkin lymphomas (NHL) were carried out in the transplantation centres of the Polish Pediatric Group for Treating Leukemias and Lymphomas (PPGLBC). In 2 patients the transplantations were carried out twice. The age of children at the moment of the transplantation ranged from 2.8 to 17.3 years (median 10.0), with higher representation of boys than girls. Twenty eight of the procedures were carried out in children with the diagnosis of B-cell non Hodgkins lymphoma (B-NHL), eight--in children with non B-cell non Hodgkins lymphoma (NB-NHL) and thirteen--in patients with anaplastic large cell lymphoma (LCAL). 16 procedures were performed in children who at the moment of transplantation were in their first complete remission (CR), another 16 were carried out while in their 2nd and 3rd CRs, and 17 transplants were performed at partial remission (PR). In addition, two children received transplants in the phase of the disease relapse. In most cases (44) the BEAM protocol was applied as megachemotherapy. In 49 procedures peripheral blood was the source of stem-cells, in one--bone marrow, in one--bone marrow + peripheral blood. The number of CD34/kg cells transplanted ranged from 1.2 x 10(6) to 8.0 x 10(6) (median 4.2 x 10(6)). Hematologic reconstitution occurred in all but one patient who died on the 10th day from HSCT. 42 out of the 49 children (87%) survived with the observation time ranging from 1 to 94 months (median 47 months). During the observation time, 34 of children were in CR. In 15, disease relapses or progression were noted within the time ranging from 3 to 22 months from HSCT (median 6 months). Seven children died (14%) including 5 due to relapse. Expected overall survival (OS) at 5 years from transplantation for the whole group of patients was 0.85 and varied only slightly for individual categories of NHL. The probability of 5-year disease-free survival (DFS) for the whole group was 0.67 and was the highest in B-NHL (0.84) and was much lower in LCAL and in NB-NHL, 0.5 and 0.47 respectively. Our results suggest that BEAM megachemotherapy with autologous transplantation in children with NHL is a safe procedure, which at the same time improves the results of standard treatment, especially in children with NHL primary resistant to chemotherapy.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Child; Child, Preschool; Cytarabine; Disease-Free Survival; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Infant; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Melphalan; Podophyllotoxin; Poland; Retrospective Studies; Survival Analysis; Time Factors; Transplantation, Autologous; Treatment Outcome

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Catheterization, Central Venous; Catheters, Indwelling; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, B-Cell; Mediastinal Neoplasms; Melphalan; Podophyllotoxin; Radiography; Thrombosis; Transplantation, Autologous

The ability to generate reactive oxygen species, the so-called oxidative burst, is essential for neutrophils to kill infectious micro-organisms. Flow cytometry was used to study oxidative burst prior to, during, and after cytostatic therapy. Seven patients were treated according to the DexaBEAM regimen with 12 cycles monitored. Four patients were treated according to the B-NHL regimen in which nine cycles were monitored. Ten healthy volunteers were chosen as a control group without any treatment. Neutrophils were collected from heparinized peripheral blood and were stimulated by phorbol-12-myristate-13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP), and Escherichia coli. The oxidative burst was estimated by the amount of nonfluorescent dihydrorhodamine 123 converted to green fluorescent rhodamine 123. Measurements were done daily. The FMLP-induced burst was enhanced in patients before therapy as compared with the control group, whereas PMA-induced burst was decreased slightly. E. coli-, FMLP-, and PMA-induced oxidative burst decreased in both groups during cytostatic therapy. E. coli-induced burst increased again within 2 days of G-CSF treatment in vivo. FMLP-induced burst increased in the B-NHL group but decreased in the DexaBEAM group. In patients who have recovered from leukopenia the oxidative burst is still partly suppressed. PMA-induced oxidative burst measured at the start of therapy correlates with infectious complications. Thus, PMA-induced burst may be used as a simple method for evaluating the individual risk of infections during therapy. The results demonstrate the modulating effect of cytostatic drugs on the oxidative burst and may explain why some patients suffer from severe bacterial infections although the total number of granulocytes is normal.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Dexamethasone; Escherichia coli; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine; Prognosis; Respiratory Burst; Tetradecanoylphorbol Acetate

Due to their homing properties, extranodal marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT) type remain localized for long periods of time, and therefore have an excellent prognosis. However, if generalization and/or transformation into a diffuse large-cell lymphoma occurs, the prognosis deteriorates and no established treatment concepts are yet available. We report about a 57-year-old female patient with relapsed transformed stage-IV extranodal MZBL of MALT type of the entire gastrointestinal tract who was successfully treated using salvage chemotherapy followed by BEAM conditioning [BCNU 1,3-bis-2-(chloroethyl-1-nitrosourea), etoposide, cytosine arabinoside, and melphalan] and autologous peripheral stem cell transplantation. Follow-up revealed a sustained complete remission for 22 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Dose-Response Relationship, Drug; Etoposide; Female; Gastrointestinal Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Melphalan; Middle Aged; Remission Induction; Transplantation, Autologous

We encountered a 65-year-old woman with diffuse large B-cell lymphoma showing t(8;14)(q24;q32) and c-myc gene rearrangement that developed following 12 years of melphalan-based chemotherapy for multiple myeloma. Short-term remission was obtained by CHOP chemotherapy. However, shortly thereafter the patient died of an aggressive progression of lymphoma. It was suspected that the lymphoma was a secondary malignancy related to the treatment with cytotoxic agents and radiation for prolonged multiple myeloma. The chromosomal abnormality t(8;14)(q24;q32) is rare in secondary malignancies. Overexpression of c-myc by gene rearrangement may be associated with clinical courses manifested by the rapid progression of lymphoma.

Topics: Aged; Antineoplastic Agents, Alkylating; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 8; Fatal Outcome; Female; Gene Rearrangement; Genes, myc; Humans; Lymphoma, B-Cell; Melphalan; Multiple Myeloma; Neoplasms, Second Primary; Translocation, Genetic

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Doxorubicin; Hematopoietic Stem Cell Transplantation; Humans; Immunophenotyping; Lymphoma, B-Cell; Male; Melphalan; Podophyllotoxin; Prednisone; Remission Induction; T-Lymphocyte Subsets; Vincristine

Lymphomatous polyposis is a rare primary gastrointestinal lymphoma. It morphologically and immunohistochemically resembles mantle cell lymphoma, with which it shares a disappointing response rate and duration following conventional anthracyclin-containing combination chemotherapy, with a short median survival and virtually no long-term survivors. We report the use of high-dose chemotherapy with autologous stem cell transplantation in second partial remission in three patients with lymphomatous polyposis treated at the Royal Marsden Hospital. All patients achieved a complete response, and one patient remains well and disease-free 64 months following transplantation and 76 months after diagnosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Intestinal Polyps; Lymphoma, B-Cell; Male; Melphalan; Middle Aged; Prednisone; Transplantation, Autologous; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Chromosome Aberrations; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 7; Cyclophosphamide; Cytarabine; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Lymphoma, B-Cell; Lymphoma, Follicular; Melphalan; Middle Aged; Podophyllotoxin; Retrospective Studies

Chemotherapy induces high remission rates in high-grade lymphoma. However relapse remains a major problem. One approach to this is myeloablative chemotherapy with transplantation of autologous bone marrow or peripheral blood progenitor cells (PBPC). Immunological mechanisms have been suggested to play a role in the prevention of relapse after transplantation. We investigated the recovery of cellular immune functions after high-dose chemotherapy and PBPC transplantation in 5 patients with high grade non-Hodgkin's lymphoma. All patients showed rapid reconstitution of natural killer (NK) and inducible lymphokine-activated killer (LAK)-activity 10-14 days after transplantation. Four of 5 patients showed higher levels of LAK-generation in the post-transplant period compared with levels prior to myeloablative treatment. Absolute lymphocyte counts in peripheral blood reached 1.0 x 10(9)/l between days 10 and 13 with a predominance of CD8+ cells and an inversion of the CD4/CD8 ratio. Four of 5 patients had a transient increase in CD56+ and CD16+ cell counts post-transplant. No change in the proportion of CD25+ cells was noted. These results show that PBPC transplantation leads to a rapid recovery of cellular immune functions after myeloablative chemotherapy and provides evidence for an increased presence of LAK precursor cells early in the post-transplant period which can be activated by IL-2 to exert high levels of cytotoxicity.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Diseases; Busulfan; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Leukapheresis; Lymphocyte Count; Lymphocyte Subsets; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Melphalan; Mesna; Middle Aged; Podophyllotoxin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Time Factors; Treatment Outcome; Vincristine

Twenty-four children with relapsed or refractory non-Hodgkin's lymphoma underwent high-dose chemotherapy (HDC) with bone marrow transplantation (BMT). HDC comprised in all cases busulfan (16 mg/kg or 600 mg/m2), with either cyclophosphamide (200 mg/kg or 4.4 g/m2) and/or melphalan (140 mg/m2). Twenty-three of these children had received second-line therapy before receiving HDC. There were 16 B cell and eight T cell lymphomas. Twenty-three patients were evaluable at day 30 post-BMT; 19 were in complete remission, four did not respond. Eight patients are long-term survivors between 62 and 296 weeks after BMT. Among the seven children with resistant disease before HDC, only one is a long-term survivor. No toxic deaths occurred. The main adverse side effect was hepatic veno-occlusive disease which occurred in four patients, but resolved completely in all cases. Comparisons with other classic HDC regimens in relapsed childhood lymphomas show that HDC containing busulfan with BMT appears reasonably safe and is effective in refractory or relapsed lymphomas, even in these highly previously treated patients.

Topics: Adolescent; Busulfan; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hepatic Veno-Occlusive Disease; Humans; Incidence; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Male; Melphalan