melphalan and Lymphoma--Non-Hodgkin

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: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Female; Humans; Incidence; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Podophyllotoxin; Prognosis; Risk Factors; Stomatitis; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous

A patient with a stage IV mantle cell lymphoma (according to the REAL classification) was treated with high-dose chemotherapy and autologous bone marrow transplantation. One year later while on alpha-interferon immunotherapy she suffered from progressive loss of short-term memory and reported difficulties in recognizing objects. Magnetic resonance imaging (MRI) showed a vast ring-enhancing lesion of the left postcentral parietal area. Serial stereotactic biopsies disclosed progressive multifocal leukoencephalopathy without JC-virus in the cerebrospinal fluid. Therapy with subcutaneous interleukin-2 (IL-2) every other day and intrathecal cytarabine once a week was started. After 4 weeks the patient refused further treatment. Nevertheless her condition improved over the next 8 months and MRI scans showed a marked improvement in the lesions.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Encephalitis; Etoposide; Female; Humans; Immunoglobulins, Intravenous; Immunosuppression Therapy; Injections, Spinal; Interferon-alpha; Interleukin-12; Leukoencephalopathy, Progressive Multifocal; Lymphoma, Non-Hodgkin; Magnetic Resonance Imaging; Melphalan; Memory Disorders; Middle Aged; Podophyllotoxin; Transplantation Conditioning; Transplantation, Autologous; 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

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin's lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL.. Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days -7, -6, and -5, etoposide (400 mg/m2 intravenously) on days -5 and -4, and melphalan (50 mg/m2/day intravenously) on days -3 and -2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days -7, -6, and -5, etoposide (400 mg/m2/day intravenously) on days -5 and -4, and cyclophosphamide (50 mg/kg/day intravenously) on days -3 and -2. The primary endpoint was 2-year progression-free survival (PFS).. Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation.. There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.

Topics: Antineoplastic Combined Chemotherapy Protocols; Behavior Therapy; Busulfan; Cyclophosphamide; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Melphalan; Transplantation, Autologous

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

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

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

Treatment of relapse and primary progression in aggressive lymphoma remains unsatisfactory; outcome is still poor. Better treatment strategies are much needed for this patient population. The R1 study is a prospective multi-center phase I/II study evaluating a dose finding approach with a triple transplant regimen in four BEAM dose levels in patients with relapsed aggressive non-Hodgkin lymphoma. The aim of the study was to determine feasibility, toxicity, and remission rate. In a total of 39 patients (pts.) enrolled in the study, 24 pts. were evaluated in the following analysis. Twenty pts. had aggressive B cell lymphoma, and two pts. had T cell lymphoma. All evaluated patients responded to DexaBEAM with a sufficient stem cell harvest. The phase I/II study was started with BEAM dose level II. Four patients were treated at dose level II, and 20 pts. were treated at dose level III. Due to the early termination of the study, dose levels I and IV were never administered. Sixteen pts. completed therapy according to protocol, and eight pts. (33.3 %) stopped treatment early. Infections (27 %) and stomatitis (13 %) were the most frequent grade III/IV non-hematologic toxicities. Thirteen percent of patients presented with severe grade III/IV lung toxicity during modified BEAM (m-BEAM). Fourteen pts. achieved a complete response (CR), one pt. achieved no change (NC), six pts. had progressive disease (PD), and two pts. died; for one pt., outcome is not known. One-year and 3-year event-free survival (EFS) was 38 and 33 %, respectively. Overall survival (OS) after 1 and 3 years was 50 and 38 %. In conclusion, dose escalation of standard BEAM is not feasible due to toxicity.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Podophyllotoxin; Prospective Studies; Salvage Therapy; Transplantation, Autologous; Young Adult

A phase I/II trial was designed to evaluate the safety and efficacy of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT). Eligible patients had relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete remission (CR). Patients received bortezomib on days -11, -8, -5, and -2 before ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m(2)) and 3 patients were accrued to each. Any nonhematological ASCT-related toxicity >2 on the Bearman scale occurring between day -11 and engraftment defined the maximum tolerated dose (MTD). After the MTD has been reached, another 20 patients were enrolled at this dose to determine a preliminary overall response rate (ORR). Patients who were in CR or PR at day +100 were considered responders. The study enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to 73) years, with 33 males and 9 females. The most common diagnoses were MCL (23 patients) and follicular lymphoma (7 patients). The median number of prior therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to 6.98) years. Thirteen patients were treated in phase I and 29 patients were treated in phase II. The MTD was initially determined to be 1.5 mg/m(2) but it was later decreased to 1 mg/m(2) because of excessive gastrointestinal toxicity and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all 38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1 year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79% to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%), peripheral neuropathy (19%), orthostatic hypotension/vasovagal syncope (16%), and 1 patient failed to engraft. Compared with 26 MCL in CR1 historic controls treated with BEAM and ASCT, PFS was 85% and 43% for the BEAM group versus 87% and 57% for those who received bortezomib in addition to standard BEAM (V-BEAM) at 1 and 5 years, respectively (log-rank P = .37). OS was 88% and 50% for the BEAM group versus 96% and 72% for V-BEAM at 1 and 5 years, respectively (log-rank P = .78). In conclusion, V-BEAM and ASCT is feasible. T

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Carmustine; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Male; Maximum Tolerated Dose; Melphalan; Middle Aged; Pyrazines; Recurrence; Remission Induction; Survival Analysis; Transplantation, Autologous

Transformation from indolent non-Hodgkin lymphoma (NHL) to diffuse large B cell lymphoma (DLBCL) has historically been associated with a poor prognosis. A small series of autologous stem cell transplantation (ASCT) studies using conventional conditioning regimens has demonstrated durable progression-free survival (PFS) rates ranging from 25% to 47%, but data in the rituximab era are lacking. Here we report the results of a multicenter retrospective trial evaluating ASCT in patients with transformed lymphoma using the Z-BEAM conditioning regimen, which combines yttrium-90-labeled ibritumomab tiuxetan (Zevalin) with high-dose BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy. Sixty-three patients from 4 institutions were treated between 2003 and 2011. Histological confirmation of transformation was required and defined as a diagnosis of DLBCL in patients with either a prior history or concomitant diagnosis of low-grade B cell NHL. Median patient age at ASCT was 59.5 years, median number of prior regimens was 2, and all patients were exposed to rituximab. Disease status at ASCT was as follows: first complete remission (CR) (n = 30), first partial remission (n = 11), first relapse (n = 14), and at least second CR (n = 8). The median time from diagnosis of histological transformation to ASCT was 7.5 months (range, 2.8 to 116). Two-year nonrelapse mortality was 0%. Median follow-up for living patients was 28 months (range, 5 to 103). Two-year PFS was 68% (95% confidence interval, 58% to 75%), and overall survival was 90% (95% confidence interval, 80% to 95%). In conclusion, the Z-BEAM conditioning regimen for ASCT is well tolerated by patients with transformed lymphoma and demonstrates encouraging clinical outcomes.

Topics: Adult; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Autografts; Carmustine; Cytarabine; Disease-Free Survival; Female; Follow-Up Studies; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Stem Cell Transplantation; Survival Rate; Transplantation Conditioning

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Combined Modality Therapy; Cytarabine; Drug Resistance, Neoplasm; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Melphalan; Nitrogen Mustard Compounds; Transplantation, Autologous

We conducted a phase I-II study of transplantation conditioning with clofarabine-melphalan-alemtuzumab for patients with advanced hematologic malignancies. Ten patients were accrued to the phase I portion, which utilized an accelerated titration design. No dose-limiting toxicity was observed, and clofarabine 40 mg/m(2) × 5, melphalan 140 mg/m(2) × 1, and alemtuzumab 20 mg × 5 was adopted for the phase II study, which accrued 72 patients. Median age was 54 years. There were 44 patients with acute myelogenous leukemia or myelodysplastic syndromes, 27 with non-Hodgkin lymphoma, and nine patients with other hematologic malignancies. The largest subgroup of 35 patients had American Society for Blood and Marrow Transplantation high-risk, active disease. All evaluable patients engrafted with a median time to neutrophil and platelet recovery of 10 and 18 days, respectively. The cumulative incidence of treatment-related mortality was 26% at 1 year. Cumulative incidence of relapse was 29% at 1 year. Overall survival was 80% (95% confidence interval [CI], 71-89) at 100 days and 59% (95% CI, 47-71) at 1 year. Progression-free-survival was 45% (95% CI, 33-67) at 1 year. Rapid-onset renal failure was the main toxicity in the phase II study and more frequent in older patients and those with baseline decrease in glomerular filtration rate. Grade 3-5 renal toxicity was observed in 16 of 74 patients (21%) treated at the phase II doses. Clofarabine-melphalan-alemtuzumab conditioning yields promising response and duration of response, but renal toxicity poses a considerable risk particularly in older patients.

Topics: Acute Kidney Injury; Adenine Nucleotides; Adult; Age Factors; Aged; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Arabinonucleosides; Clofarabine; Female; Glomerular Filtration Rate; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Recurrence; Risk; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous

High-dose chemotherapy combined with autologous stem-cell transplantation (ASCT) is the standard therapy for refractory/relapsed aggressive lymphoma. In the era of rituximab-containing frontline regimens, it is becoming more challenging to salvage patients in this setting, and novel approaches are required. This is a randomized study evaluating the safety and efficacy of standard-dose ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy (Z-BEAM) and ASCT in refractory/relapsed aggressive lymphoma.. Forty-three patients with CD20(+) -aggressive lymphoma were randomized to a treatment arm (Z-BEAM, n = 22) or control arm (BEAM alone, n = 21). Ibritumomab tiuxetan was given at 0.4 mCi/kg on day -14 before ASCT.. Patient characteristics, engraftment kinetics, and toxicity profile were similar between the 2 groups. Two-year progression-free survival (PFS) for all patients was 48% (95% confidence interval, 32%-64%): 59% and 37% after Z-BEAM and BEAM alone, respectively (P = .2). Multivariate analysis identified advanced age (hazard ratio [HR], 8.3; P = .001), high-risk disease (relapse within 12 months of diagnosis and/or secondary International Prognostic Index >2; HR, 2.8; P = .04), positive positron emission tomography-computed tomography pretransplant (HR, 2.4; P = .07), and BEAM alone (HR, 2.8; P = .03) as poor prognostic factors. Intermediate-risk patients with 1 or 2 risk factors had better PFS with Z-BEAM compared with BEAM: 69% and 29%, respectively (P = .07). Two-year overall survival was 91% and 62% after Z-BEAM and BEAM, respectively (P = .05). Similar prognostic factors determined survival. The HR for BEAM alone in the multivariate analysis was 8.1 (P = .01).. Standard-dose ibritumomab tiuxetan combined with BEAM high-dose chemotherapy is safe and possibly more effective than BEAM alone as a conditioning regimen for ASCT in the era of rituximab-containing chemotherapy regimens.

Topics: Adult; Aged; Analysis of Variance; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Disease-Free Survival; Drug Administration Schedule; Early Termination of Clinical Trials; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Odds Ratio; Prognosis; Proportional Hazards Models; Recurrence; Risk Factors; Sample Size; Stem Cell Transplantation; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

A total of 20 patients enrolled in a multicenter phase II dose escalation study of radioimmunotherapy (RIT) using yttrium-90-ibritumomab tiuxetan at two dose levels (22 and 30 MBq/kg) in 10 patients, combined with reduced intensity conditioning (RIC) using fludarabine, melphalan and alemtuzumab followed by allogeneic hematopoietic cell transplantation (HCT) from either matched-related (n=5) or matched-unrelated donors (n=15). Postgrafting immunosuppression with cyclosporine was administered. Diagnoses were diffuse large B-cell lymphoma (n=13), transformed CLL (n=4), blastic mantle cell lymphoma (n=2) and follicular lymphoma grade 3 (n=1). Median age was 51 (range, 29-69) years. All patients were high risk with relapsed/refractory disease or relapse after preceding autologous HCT. Median follow-up of patients alive was 1115 (range, 1006-1252) days. No directly RIT-related toxicities were observed. The cumulative incidence of non-relapse mortality was 30%. Incidences of grade II-IV acute and chronic GvHD was 45% and 70%, respectively. Kaplan-Meier estimated 3-year OS and EFS were 20% for both dose levels. In conclusion, dose escalation of RIT and combined use with RIC is feasible with no additional toxicity due to dose escalation. This study is registered on http://clinicaltrials.gov as NCT00302757.

Topics: Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cyclosporine; Dose-Response Relationship, Radiation; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Grading; Prognosis; Prospective Studies; Radioimmunotherapy; Radiopharmaceuticals; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Yttrium Radioisotopes

A standard salvage therapy of relapsed/refractory aggressive non-Hodgkin lymphoma (NHL) comprises autologous stem cell transplantation (ASCT) after chemotherapy conditioning with carmustine, etoposide, cytarabine, and melphalan (BEAM) regimen. However, the achievement of long-term disease-free survival remains challenging. We have introduced concomitant (131)I-rituximab radioimmunotherapy (RIT) in an attempt to effect the elimination of lymphoma cells. Our phase II physician-sponsored study of 16 consecutive patients with relapsed, refractory, aggressive B-cell NHL reports a median 44 month follow-up after (131)I-rituximab-BEAM conditioning therapy and ASCT. Prospective personalized dosimetry performed in each patient limited the whole body radiation absorbed dose to 0.75 Gy. RIT (131)I-rituximab was administered on an outpatient basis on day -15 before ASCT. The BEAM conditioning regimen was commenced on day -6. Evaluable engraftment data are available for 15 patients who had 16 ASCTs. Engraftment was achieved in all patients, 15 out of 16 ASCTs achieved a complete response, and 1 out of 15 ASCTs achieved a partial response. Twelve out of sixteen patients remained alive and disease free at a median of 44 months (range 4-108 months) post-ASCT. This study suggests that the addition of (131)I-rituximab RIT to BEAM conditioning, before ASCT, for relapsed or primary refractory B-cell NHL improves disease eradication, compared with BEAM conditioning alone, without significant additional toxicity. In particular, there is an impression of improved disease control in the subset of patients with transformed follicular and mantle cell lymphomas.

Topics: Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Disease-Free Survival; Etoposide; Humans; Iodine Radioisotopes; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; Radioimmunotherapy; Rituximab; Salvage Therapy; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Autologous

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 compared the efficacy and toxicity of BEAM (BCNU, etoposide, cytarabine and melphalan) and BuCyE (busulfan, cyclophosphamide and etoposide), given prior to autologous stem cell transplantation (ASCT), in 65 patients with non-Hodgkin's lymphoma. Of these 65 patients, 43 received BEAM and 22 received BuCyE. Their age, gender distribution, International Prognostic Index, status of disease at ASCT and median number of infused CD34(+) cells/kg were similar. Neutrophil and platelet engraftment were significantly faster in the BuCyE group. Rates of mucositis, nausea/vomiting, diarrhea, bleeding and infections were similar in the two groups. Median overall survival and event-free survival did not differ significantly between the two groups. These findings indicate that BuCyE is an effective conditioning regimen, showing similar survival outcomes and toxicity profiles as BEAM. Furthermore, hematologic recovery is significantly faster in patients given the BuCyE conditioning regimen.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carmustine; Cyclophosphamide; Cytarabine; Disease-Free Survival; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

The introduction of plerixafor has enabled successful collection of stem cells in the majority of patients with lymphoma or myeloma in whom previous attempts at mobilization have failed. However, a proportion of patients have been shown to be resistant to this mobilization regimen. To identify the factors that impair stem cell mobilization and collection with plerixafor, we reviewed the data for 197 patients who had undergone mobilization with plerixafor and granulocyte-colony stimulating factor in Central Europe. Predictors of mobilization failure were evaluated using logistic regression analysis. Among the 197 patients mobilized, the target of ≥2.0 × 10(6) CD34+ cells/kg was collected from 133 (67.5%). Our analysis revealed that previous treatment with lenalidomide, bortezomib, melphalan, radiotherapy, or autologous stem cell transplantation and regimen of plerixafor use in combination with chemotherapy had no significant effect on the efficiency of collection. In contrast, an age ≥65 years (odds ratio 0.331, 95% CI: 0.112-0.977, P < 0.05), a diagnosis of non-Hodgkin's lymphoma (odds ratio 0.277, 95% CI: 0.124-0.622, P < 0.01), and treatment with ≥ four chemotherapy regimens (odds ratio 0.366, 95% CI: 0.167-0.799, P < 0.05) were associated significantly with failed mobilization. The rate of successful mobilizations was decreased in patients treated with purine analogues (odds ratio 0.323, 95% CI: 0.096-1.094, P = 0.07) but increased in female patients (odds ratio 1.961, CI: 0.943-4.080, P = 0.07). Patients who are characterized by the above negative features could benefit potentially from further improvement in the mobilization strategy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Antineoplastic Agents; Benzylamines; Boronic Acids; Bortezomib; Child; Cyclams; Europe; Female; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Heterocyclic Compounds; Humans; Lenalidomide; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Myeloablative Agonists; Prognosis; Pyrazines; Thalidomide; Transplantation, Autologous; Transplantation, Homologous

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

Evaluation of therapeutic response in non-Hodgkin's lymphoma (NHL) patients with autologous stem cell transplantation (ASCT) is of great clinical significance. But the exact role of (18)F-fluorodeoxyglucose (FDG) imaging in NHL associated with ASCT is unclear. This study assessed the predictive value of (18)F-FDG hybrid PET/CT imaging for the clinical outcome such as progression-free survival (PFS) in patients with NHL prior to and after ASCT.. (18)F-FDG hybrid PET/CT was performed in 31 patients (24 male and 7 female) with pathologically confirmed NHL prior to and after ASCT. Mean age was 43.1+/-13.8 years. No patients were lost to follow-up earlier than 1 year from ASCT. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of (18)F-FDG hybrid PET/CT before ASCT were compared to the results after ASCT. The results of pre- and post-ASCT FDG hybrid PET/CT findings were correlated to PFS using Kaplan-Meier survival analysis. Regression analyses were employed to test for independence of established prognostic factors.. Sixteen of 31 patients (52%) progressed/relapsed or died after a median follow-up of 7 months, the remaining 15 patients (48%) were disease free after a median follow-up of 24 months. Both pre- and post-ASCT, (18)F-FDG hybrid PET/CT findings showed high PPV, NPV and accuracy (85.7 versus 92.3%, 76.5 versus 77.8% and 80.6 versus 83.9%). Both pre- and post-ASCT, (18)F-FDG hybrid PET/CT findings were strongly correlated with PFS (P<0.0005, significant). Of pre- ASCT FDG finding, the 1-year PFS rate for FDG-negative and FDG-positive patients was 88.2 and 28.6%. Of post-ASCT FDG finding, the 1-year PFS rate for FDG-negative patients and FDG-positive patients was 88.9 and 23.1%. The regression model showed that the predictive value of FDG imaging owed its significance to the very high hazard ratio between patients with positive FDG imaging and negative FDG imaging (P<0.005) both pre- and post-ASCT.. (18)F-FDG hybrid PET/CT imaging prior to and following autologous stem cell transplantation in NHL contains predictive information on the long-term clinical outcome.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Child; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Disease-Free Survival; Doxorubicin; Etoposide; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Positron-Emission Tomography; Predictive Value of Tests; Prednisolone; Prednisone; Proportional Hazards Models; Radiopharmaceuticals; Rituximab; Teniposide; Tomography, X-Ray Computed; Transplantation, Autologous; Treatment Outcome; Vincristine; Young Adult

Alpha interferon has proven efficacy in prolonging remissions in patients with follicular non-Hodgkin lymphoma (NHL) when given concurrently with or after conventional-dose anthracycline-based chemotherapy, but there are limited data on its use after myeloablative conditioning. We prospectively evaluated the toxicity and efficacy of interferon given thrice weekly for up to 5 years post-engraftment in patients with relapsed follicular NHL undergoing autologous stem cell transplant using busulfan-melphalan conditioning. Thirty-seven patients were enrolled in this Australasian Leukaemia & Lymphoma Group study and transplanted between 1995 and 1999. Only one patient had received prior rituximab. Two patients died of transplant-related toxicity; 28 of the remainder commenced interferon, but it was discontinued prematurely in most patients due to toxicity (mainly fatigue and depression) or relapse. While the majority of patients (29/36 evaluable: 81%) achieved a complete remission based on clinical and CT scan criteria post-transplant, most relapsed relatively early, with a median progression-free survival of 2.4 years. The overall survival at 7 years was 49%. Eight patients (22%), however, remain alive a median of 9.3 years post-transplant, having never relapsed, and another six patients (16%) remain alive in durable remission after salvage therapy. These results demonstrate that interferon is poorly tolerated post-autograft and hence is unlikely to positively contribute to patient outcome. Long-term follow-up demonstrates that autografting may result in durable remissions in a meaningful minority of patients with relapsed follicular NHL.

Topics: Adult; Busulfan; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Interferons; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Prognosis; Recurrence; Remission Induction; Salvage Therapy; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Young Adult

Filgrastim decreases the time to neutrophil recovery after autologous peripheral blood stem cell transplantation (PBSCT). We hypothesized that single-dose pegfilgrastim would mimic multiple daily doses of filgrastim, resulting in an equivalent shortening of post-PBSCT neutropenia.. Patients who were eligible for PBSCT and aged >or= 18 years were identified before high-dose chemotherapy, after the harvesting and cryopreservation of peripheral blood progenitor cells (ie, > 2.5 x 10(6) CD34-positive cells/kg). Eligible patients received either standard carmustine/etoposide/cytarabine/melphalan (BEAM) or carmustine/etoposide/cytarabine/cyclophosphamide (BEAC) high-dose chemotherapy. Before high-dose chemotherapy, patients were randomly assigned to receive pegfilgrastim 6 mg on day 1 (arm A) or weight-based, dose-adjusted filgrastim beginning on day 1 (arm B) after transplantation until neutrophil engraftment.. One-hundred and one patients were enrolled between April 2003 and April 2007. Three patients were not treated. Demographics were well-balanced in terms of stage at diagnosis, Eastern Cooperative Oncology Group performance status, histology, and lines of previous therapy. Results (arm A/arm B) pertained to mean doses received (1.0/12.6), mean absolute neutrophil count recovery days (9.3/9.8), red blood cell transfusions (1.7/1.9), red blood cell transfusion units (3.1/3.8), platelet transfusions (3.1/2.8), positive blood culture rate (18%/29.2%), febrile neutropenia (FN; 18%/16.7%), and duration of FN (days; 7.1/6.9). Transplantation-related mortality and grade 3 or 4 adverse events were comparable between arms.. Pegfilgrastim after PBSCT appears equivalent to multiple daily doses of filgrastim. This approach might be considered in lieu of filgrastim, thus obviating the need for multiple daily injections.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Staging; Neutropenia; Podophyllotoxin; Polyethylene Glycols; Recombinant Proteins; Transplantation, Autologous; Young Adult

This phase II trial evaluated the safety and efficacy of combining yttrium-90 (90Y) ibritumomab tiuxetan with high-dose carmustine, cytarabine, etoposide, and melphalan (BEAM) and autologous stem-cell transplantation in patients with non-Hodgkin's lymphoma who were considered ineligible for total-body irradiation because of older age or prior radiotherapy.. Between May 2002 and January 2006, 14 days before autologous stem-cell transplantation, 41 patients with non-Hodgkin's lymphoma received standard-dose 90Y ibritumomab tiuxetan (14.8 MBq/kg [0.4 mCi/kg]) followed by high-dose BEAM.. The median age was 60 years (range, 19 to 78 years), and the median number of previous therapies was two (range, one to six). Disease histologies were diffuse large B-cell (n = 20), mantle cell (n = 13), follicular (n = 4), and transformed lymphoma (n = 4). With a median follow-up of 18.4 months (range, 5.5 to 53.3 months) the estimated 2-year overall and progression-free survival were 88.9% (95% CI, 75.3% to 95.2%) and 69.8% (95% CI, 56.4% to 79.7%). The median time to WBC engraftment was 11 days (range, 9 to 26 days) and time to platelet engraftment was 12 days (range, 3 to 107 days). Adverse events were similar to those seen historically with high-dose BEAM alone, and included grade 3 or 4 pulmonary toxicity in 10 patients.. Adding 90Y ibritumomab tiuxetan to high-dose BEAM with autologous stem-cell transplantation is feasible and has a toxicity and tolerability profile similar to that observed with BEAM alone. Rates of progression-free survival seen in these patients are promising and warrant additional study.

Topics: Adult; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Female; Humans; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Podophyllotoxin; Radioimmunotherapy; Stem Cell Transplantation; Treatment Outcome; Yttrium Radioisotopes

Growth factors are frequently used to aid peripheral blood progenitor cell mobilization from bone marrow. This phase 2 study examined the efficacy and safety of pegfilgrastim for mobilizing peripheral blood progenitors cells for autologous transplantation.. Patients with non-Hodgkin's lymphoma received one cycle of mobilizing chemotherapy (ifosfamide, carboplatin and etoposide, ICE). Twenty-four hours later they were randomized, double-blind, to receive a single dose of pegfilgrastim 6 mg or 12 mg, or filgrastim 5 mug/kg/day (until the end of leukapheresis). Following leukapheresis (collection phase), patients rested or received one or two 'salvage' cycles of ICE. High-dose BEAM chemotherapy was then given before peripheral blood progenitor cell transplantation. The primary end-point was the patients' mean yield of CD34(+) cells/kg during the collection phase.. Ninety patients were randomized and received a study drug; 63% completed the collection phase. The patients' mean (95% CI) CD34(+) cell harvest per leukapheresis was 0.8 (0.5-1.4), 0.8 (0.5-1.6) and 1.2 (0.7-2.0)x10(6) cells/kg for the pegfilgrastim 6 mg, pegfilgrastim 12 mg and filgrastim groups, respectively. Twenty (69%), 17 (59%) and 23 (72%) patients in these three groups achieved the targeted minimum harvest (>/=2 x 10(6) cells/kg). The mean total harvests were 1.7, 1.4 and 2.2 x 10(6) cells/kg, respectively. Post-transplantation, the median days to absolute neutrophil count recovery (>/=0.5 x 10(9)/L) were 12, 11, and 11, respectively. Pegfilgrastim and filgrastim were generally well tolerated.. Pegfilgrastim (6 or 12 mg) was effective for mobilizing peripheral blood progenitors cells in patients with non-Hodgkin's lymphoma. These data may aid the design of studies to clarify optimal dosing and leukapheresis with pegfilgrastim.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Carboplatin; Carmustine; Cytarabine; Double-Blind Method; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Polyethylene Glycols; Recombinant Proteins; Transplantation, Autologous

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

To determine the safety and outcome following standard-dose ibritumomab tiuxetan followed by BEAM high-dose chemotherapy and autologous stem cell transplantation (ASCT) in patients with chemo-refractory aggressive non-Hodgkin's lymphoma.. The study included 23 patients, median age 55 years (range, 35-66) with chemo-refractory lymphoma, either primary refractory (n = 11) or in refractory relapse (n = 12). Rituximab 250 mg/m(2) followed by ibritumomab tiuxetan 0.4 mCi/kg were given on day -14 and high-dose BEAM chemotherapy started on day -6.. All patients engrafted. Twenty-one patients are evaluable for response; 11 achieved CR, 9 achieved PR, 5 of whom converted to CR with additional radiation therapy (overall CR rate 76%). With a median follow-up of 17 months (range, 4-27) 16 patients are alive and 12 are progression-free. The estimated 2-year overall and progression-free survival are 67% (95% CI, 46-87%) and 52% (95% CI, 31-72%), respectively. The day-100 rate of treatment-related mortality was 9% (95% CI, 2-33%) and the 2-year cumulative incidence of relapse was 31% (95% CI, 17-57%). Extensive prior therapy (>3 lines), high LDH and IPI score at ASCT, bulky disease, and progression during last chemotherapy were risk factors for reduced survival.. Ibritumomab tiuxetan-BEAM and ASCT is relatively safe and may improve outcome in patients with refractory lymphoma. Although excess nonrelapse mortality can not be ruled out, relapse rate was relatively low, resulting in improved outcome. Standard-risk patients with chemo-sensitive disease may also benefit from ibritumomab tiuxetan-BEAM and ASCT. This hypothesis merits further study in larger-scale prospective randomized studies.

Topics: Adult; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Female; Granulocyte Colony-Stimulating Factor; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Salvage Therapy; Stem Cell Transplantation; Transplantation Conditioning; Treatment Outcome

A single center, prospective clinical trial was conducted evaluating 2 cycles of induction high-dose chemotherapy for adults younger than 65 years of age with aggressive non-Hodgkin lymphoma (NHL) and 2 to 3 Age-Adjusted International Prognostic Index risk factors. Patients received one cycle of standard dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by one cycle of dose-intensive cyclophosphamide 5.25 g/m(2), etoposide 1.05 g/m(2), cisplatin 105 mg/m(2) (DICEP), then underwent autologous blood stem cell collection, followed by one cycle of high-dose carmustine (BCNU) 300 mg/m(2), etoposide 800 mg/m(2), Ara-C 1600 mg/m(2), melphalan 140 mg/m(2) (BEAM), and autologous stem cell transplantation (ASCT) and radiotherapy to prior bulk. From June 1998 to August 2004, 55 patients aged 20 to 63 years (median 44 years) were accrued, 51 (92%) of whom had diffuse large B-cell NHL. Poor prognostic factors included stage 4 (n = 46), elevated lactate dehydrogenase (LDH; n = 47), Eastern Cooperative Oncology Group (ECOG) performance status 2 to 4 (n = 43), bulky mass more than 10 cm (n = 34), and marrow involvement (n = 16). Only one patient experienced nonrelapse mortality. With a median follow-up of 49 months, 4-year event-free survival (EFS) and overall survival (OS) rates for all 55 patients are 72% (95% confidence interval [CI] = 60%-84%) and 79% (95% CI = 69%-90%), respectively. In conclusion, CHOP-DICEP-BEAM is feasible and gave encouraging EFS and OS for patients with poor-prognosis aggressive NHL.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; L-Lactate Dehydrogenase; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Prednisone; Prognosis; Prospective Studies; Recurrence; Remission Induction; Risk Factors; Stem Cell Transplantation; Survival Rate; Transplantation, Autologous; Vincristine

To investigate the feasibility and efficacy of high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) for patients with newly diagnosed aggressive and relapsed non-Hodgkin's lymphoma (NHL), we administered LEED, a drug-only HDCT regimen consisting of melphalan, cyclophosphamide, etoposide, and dexamethasone, followed by ASCT in this single-institution trial. Furthermore, rituximab was added to the LEED regimen (R-LEED) for patients with CD20+ NHL. Twenty-six patients in the LEED group and 24 patients in the R-LEED group were enrolled and assessed for this study. All patients achieved complete engraftment after ASCT. As for the nonhematologic toxicities, infection toxicities of grades 3 and 4 were observed in 9 patients (34.6%) of the LEED group and 12 patients (50%) of the R-LEED group. Four patients (15.4%) in the LEED group and 5 (20.8%) in the R-LEED group developed grade 3 toxicity in the elevation of aspartate aminotransferase/alanine aminotransferase levels. Other grade 4 toxicities were rare in both groups. With a median follow-up time from the date of ASCT of 30 months in the LEED group and 18 months in the R-LEED group, the overall survival rates were 66.5% and 78.2%, respectively. These results suggested that LEED, as well as R-LEED, was a safe and feasible high-dose regimen for aggressive and relapsed NHL.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dexamethasone; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Recurrence; Rituximab; Stem Cell Transplantation; Transplantation, Autologous

To determine the maximum outpatient dose of iodine-131 tositumomab (up to 0.75 Gy) combined with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem-cell transplantation (ASCT) for the treatment of chemotherapy-resistant relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).. Twenty-three patients with chemotherapy-refractory or multiply-relapsed B-cell NHL were treated in a phase I trial combining iodine-131 tositumomab (ranging from 0.30 to 0.75 Gy total-body dose [TBD]) with high-dose BEAM followed by ASCT.. The complete response rate after transplantation was 57%, and the overall response rate was 65%. Short-term and long-term toxicities were similar to historical control patients treated with BEAM alone. With a median follow-up of 38 months (range, 27 to 60 months), the overall survival (OS) rate was 55%, and the event-free survival (EFS) rate was 39%.. There were no significant added toxicities apparent with the addition of iodine-131 tositumomab up to a dose of 0.75 Gy TBD to high-dose BEAM chemotherapy followed by ASCT. The EFS and OS were encouraging in this group of chemotherapy-resistant or refractory B-cell NHL patients. A follow-up phase II trial with iodine-131 tositumomab at the dose of 0.75 Gy TBD with BEAM is currently ongoing.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, CD20; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Etoposide; Female; Humans; Iodine Radioisotopes; Lymphoma, Non-Hodgkin; Male; Maximum Tolerated Dose; Melphalan; Middle Aged; Radioimmunotherapy; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

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

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

The study included 29 patients with high-grade non-Hodgkin's lymphoma. Nine patients (group 1) received 6-8 cycles of CHOP, another 20-6 cycles of CHOP and Dexa-BEAM followed by autologous hemopoietic cell transplantation with CBV or BEAM conditioning regimen (bone marrow or peripheral stem cells) (group 2). The groups were comparable as far as gender and age are concerned. Overall 5-year survival was in 24.1 and 71.4%, respectively. Double CHOP-Dexa-BEAM plus autologous hemopoietic cell transplantation proved superior to standard CHOP-therapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Prednisone; Survival Analysis; Transplantation, Autologous; Treatment Outcome; Vincristine

High-dose chemotherapy supported by autologous stem cell transplantation is widely used in patients with non-Hodgkin's lymphoma (NHL). Limited data is available on the comparative toxicity and efficacy of various high-dose regimens applied in NHL. We therefore analysed regimen-related toxicity and outcome in 71 consecutive NHL patients who received either BEAC (N = 36) or BEAM (N = 35) supported by peripheral blood progenitor cell infusion plus granulocyte colony-stimulating factor. The patients who received BEAM had significantly more often WHO grade > 2 mucositis (63 vs. 28%, P = 0.009) and diarrhoea grade >2 (29 vs. 8%, P = 0.062). Septicaemia also tended to be more frequent and the peak CRP value was higher in the BEAM group (140 vs. 113 mg/l, P = 0.034). Transplant-related mortality (< 100 d) was 3 and 9% in the BEAC and BEAM groups, respectively. No significant differences were observed in overall survival or progression free survival between these two groups. While BEAC and BEAM appears to have equal antitumour efficacy in patients with NHL, BEAM seems to be more toxic to the gastrointestinal tract. However, randomised studies are needed for more definitive conclusions on the relative merits of various high-dose regimens in patients with NHL.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Prognosis; Survival Rate; Transplantation, Autologous

This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study.. Three hundred twelve patients with "aggressive" non-Hodgkin's lymphoma aged

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Chemotherapy, Adjuvant; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Germany; Humans; L-Lactate Dehydrogenase; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Prednisolone; Prognosis; Prospective Studies; Radiotherapy, Adjuvant; Risk; Stem Cell Transplantation; Survival Analysis; Transplantation, Autologous; Treatment Outcome; Vincristine

The study included 70 patients with high-grade malignant non-Hodgkin's lymphoma (Kiel) who received the following treatment: group 1(24)--6-8 cycles of CHOP; group 2 (relapse or tumor progression after standard chemotherapy--13)--6 cycles of CHOP and Dexa-BEAM, and group 3 (relapse or tumor progression after standard chemotherapy--8)--6 cycles of CHOP plus Dexa-BEAM plus autologous hemopoietic cell transplantation with CBV or BEAM conditioning regimen (bone marrow or peripheral stem cells). The groups were comparable as far as gender and age are concerned. Overall 5-year survival rates were 81, 20 and 48%, respectively. CHOP-Dexa-BEAM plus autologous hemopoietic cell transplantation proved superior to CHOP-Dexa-BEAM alone.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Prednisone; Survival Analysis; Transplantation, Autologous; Treatment Outcome; Vincristine

The purpose of the present study was to evaluate the feasibility and the efficacy of employing a high-dose chemotherapy (HDT) regimen with tandem peripheral blood progenitor cells (PBPC) supported transplantation in the initial treatment of aggressive non-Hodgkin's lymphoma (NHL). HDT was preceded by a standard course of conventional dose chemotherapy in 17 out of the 25 patients treated, while in 8 cases it was delivered after only one or two cycles. HDT was a three-step procedure which included high-dose (6-7 g/m2) cyclophosphamide (CY) supported by haematopoietic growth factors, the first myeloablative course with mitoxantrone (NOV) 60, 75 or 90 mg/m2 plus melphalan (L-PAM) 140-180 mg/m2 with haematopoietic rescue, and the second myeloablative course with etoposide (VP) and carboplatin (CARBO) given at 1.5 g/m2 each with haematopoietic rescue. PBPC were collected after CY administration. Twenty-two patients (88%) completed the HDT, haematological reconstitution was rapid and complete at each step and there were no toxic deaths. The activity of the treatment was high with a CR rate over 90% in the entire patient population. The 2-year overall survival (OS) and failure-free survival (FFS) rates of patients in both Age-Adjusted International Prognostic Index (A-AIPI) groups 2 and 3 are 79% and the disease-free survival (DFS) rate for the CRs is 85%. In A-AIPI group 1 the 2-year OS and FFS rates are both 91%.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Etoposide; Feasibility Studies; Female; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Humans; Life Tables; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mitoxantrone; Remission Induction; Salvage Therapy; Survival Analysis; Survival Rate; Treatment Outcome

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

Patients with NHL and two or three factors of the International Prognostic Index (IPI) have a poor prognosis. We performed a prospective trial of intensive induction therapy followed with high-dose consolidation in such patients to determine the feasibility of this approach, as well as the response rate and survival. Untreated patients with aggressive lymphoma under the age of 60 with two or three adverse prognostic factors (disseminated stage, increased serum LDH, ECOG performance status >1) were prospectively included between June 1995 and April 1998 in a trial evaluating intensive induction chemotherapy with the ACE regimen (adriamycin day 1; cyclophosphamide days 1-2; etoposide days 1-3), with G-CSF support. Patients in complete remission after induction received one course of intensification with stem cell support (BEAM regimen), whereas patients in partial response received two intensifications (BEAM, then ICE regimens). Thirty-three patients (median age 38 years) were included. All patients presented WHO grade 4 leukopenia and 84% grade 3-4 thrombocytopenia during induction. There was one toxic death during induction. Twenty-nine patients proceeded to high-dose consolidation, including 12 patients who received a second high-dose treatment. The overall response rate was 88% (95% CI 76-99%), both after induction therapy and treatment completion. Thirty-nine percent of the patients had achieved complete remission after induction, and 73% after treatment completion. With a median follow-up after treatment onset of 29 months, the projected 3-year overall survival was 71% (95% CI 64-78%) and the event-free survival 58% (95% CI 50-66%). Event-free survival was significantly shorter in patients who did not achieve CR after induction therapy or after treatment completion. Early therapeutic intensification after intensive induction chemotherapy is feasible in patients with poor prognosis aggressive NHL and shows promising response and survival rates.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Etoposide; Feasibility Studies; Female; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Prognosis; Prospective Studies; Treatment Outcome

The aim of the present study was to evaluate the feasibility and response of the Dexa-BEAM regimen as a salvage therapy followed by high-dose chemotherapy (HDCT) with peripheral blood stem cell transplantation (PBCST) in responding patients with high-grade relapsed or resistant aggressive non-Hodgkin's lymphoma (NHL). Sixteen pretreated patients (mean age 44, range 26-59) with relapsed (8) or resistant (8) NHL were treated with 1-4 cycles of Dexa-BEAM (dexamethasone, BCNU, etoposide, cytarabine, melphalan) in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received HDCT with PBSCT. The conditioning regimen used was BEAM. Three patients achieved CR and one patient PR, resulting in an overall response rate of 25%. Three of four responding patients underwent high-dose chemotherapy and were successfully transplanted with autologous blood stem cells. Progressive disease developed in one patient after transplantation. Myelosuppression (WHO grade III- grade IV), the major side effect, was observed in all courses of Dexa-BEAM. Myelosuppression-related infection WHO grade IV occurred in four patients. The protocol was not well tolerated in this heavily pretreated group of patients with four severe myelosuppression-related infections WHO grade IV and one treatment-related death. The overall response rate in this study is not comparable to other salvage regimens published and led to the discontinuation of the trial. In conclusion Dexa-BEAM was only effective in a minority of patients with refractory or relapsed aggressive NHL and was not useful as a cytoreductive regimen prior to HDCT.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Dexamethasone; Drug Resistance, Multiple; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukocyte Count; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Staging; Recurrence; Survival Analysis; Time Factors

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

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

In this phase II trial, we used a double dose-intensive chemotherapy and stem cell rescue protocol to treat breast cancer (BCA) patients or non-Hodgkin's lymphoma patients (NHL). The first cycle consisted of high-dose melphalan followed by ABMT. The second cycle used a novel chemotherapy combination; thiotepa, etoposide, carboplatin and cyclophosphamide (TECC) followed by ABMT. We treated 12 patients in total, nine with BCA, three with NHL. All nine BCA patients were treated with the two cycle protocol. The three NHL patients were treated with the second cycle only. Bone marrow (BM, 1 patient), peripheral blood stem cells (PBSC, 10 patients) or both (1 patient) were reinfused 60-72 h after completion of each cycle of chemotherapy. Recovery was rapid; the ANC rose to greater than 500/microl on day +11 (+8 to + 20) and the platelet count to greater than 20000/microl on day +12 (+6 to +20). The toxicities included the expected neutropenic fevers, severe mucositis, diarrhea, and a low incidence of mild renal insufficiency. No patients developed veno-occlusive disease, hemorrhagic cystitis or overt bleeding. With a mean follow-up of 37 months, 83.3% of the patients are alive. Six patients are in complete remission; one patient with BCA relapsed and expired; one patient with NHL is in CR now over 18 months after relapse and subsequent treatment with interferon; one patient is too early to evaluate. Progression-free survival overall is 75%, which is at least equivalent to many other recent studies using similar regimens. In addition, we have also found that delayed addition of G-CSF during the mobilization of PBSC was feasible and resulted in excellent CD34+ cell counts and engraftments, and reduced treatment costs. These results indicate that this chemotherapy is effective with good remission rates and high progression-free survival rates. It is also well tolerated with acceptable toxicities that are manageable. Long-term follow-up of a larger cohort of patients will be needed to ascertain the overall efficacy of this type of therapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Breast Neoplasms; Carboplatin; Cyclophosphamide; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Recurrence; Thiotepa; Transplantation, Autologous

The survival of two cohorts of patients with stage III/IV large-cell lymphomas treated by CHOP has been compared. In the first cohort of 88 patients (1974-1982), high-dose therapy with autologous bone marrow transplantation (ABMT) was not available as salvage therapy and in the second cohort of 87 patients (1987-1992), this was the recommended salvage for patients with disease that was still chemosensitive to conventional-dose therapy. The actuarial overall survivals at five years were 40% and 44% in the first and second cohorts, respectively, indicating that the availability of ABMT had made little impact. Of the 62 patients in the second cohort who failed CHOP therapy, 8 died before second-line chemotherapy could be given, 1 refused more therapy, and 8 were considered unsuitable for further combination chemotherapy. Seven patients with localized disease remaining received local radiotherapy. Of the 38 patients given salvage therapy, 14 had chemoresistant disease. Only 9 patients received high-dose BEAM chemotherapy and ABMT, and 7 remain disease-free. ABMT was restricted to a highly select patient group, and as a result more widespread application of this strategy might result in only a modest further improvement.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cohort Studies; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dose-Response Relationship, Drug; Doxorubicin; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Staging; Podophyllotoxin; Prednisone; Salvage Therapy; Treatment Outcome; Vincristine

Mantle cell lymphoma (MC) is not curable with conventional chemotherapy. To improve the prognosis of patients with this disease, we prospectively studied an intensive sequential therapy consisting of the Dexa-BEAM regimen (dexamethasone, BCNU, etoposide, ara-C, melphalan) followed by myeloablative therapy with autologous stem cell reinfusion.. Nine consecutive patients with stage III/IV MC were included. Two had untreated disease, four were in first remission, whereas three had more advanced disease. All patients underwent one to two cycles of Dexa-BEAM chemotherapy to reduce the tumor load and to mobilize peripheral blood progenitor cells (PBPC). Subsequently, patients were treated with high-dose radiochemotherapy followed by PBPC reinfusion and were prospectively analyzed for residual disease by clinical methods as well as by PCR amplification clonal CDRIII rearrangements.. With an overall response rate of 100%, the initial Dexa-BEAM cycles effectively reduced the tumor load. All patients proceeded to high-dose therapy and subsequent stem cell rescue. Engraftment was prompt, and procedure-related deaths did not occur. With a median follow-up of 12 (3-33) months post transplant, all patients are alive in continuing clinical and molecular remission.. Sequential intensive therapy consisting of Dexa-BEAM and high-dose radiochemotherapy appears to be a highly effective treatment for patients with MC. However, the data are still preliminary, and larger patient numbers and a longer follow-up are required.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Dexamethasone; Dose-Response Relationship, Drug; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunophenotyping; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Staging; Prospective Studies; Transplantation, Autologous

The optimal use of mitoxantrone (NOV) in the high-dose range requires elucidation of its maximum tolerated dose with peripheral blood progenitor cell (PBPC) support and the time interval needed between drug administration and PBPC reinfusion in order to avoid graft toxicity. The aims of this study were: (1) to verify the feasibility and haematological toxicity of escalating NOV up to 90 mg m(-2) with PBPC support; and (2) to verify the safeness of a short (96 h) interval between NOV administration and PBPC reinfusion. Three cohorts of ten patients with breast cancer (BC) or non-Hodgkin's lymphoma (NHL) received escalating doses of NOV, 60, 75 and 90 mg m(-2) plus melphalan (L-PAM), 140-180 mg m(-2), with PBPC rescue 96 h after NOV. Haematological toxicity was evaluated daily (WHO criteria). NOV plasma pharmacokinetics was also evaluated, as well as NOV cytotoxicity against PBPCs. Haematological recovery was rapid and complete at each NOV dose level without statistically significant differences, and there were no major toxicities. NOV plasma concentrations at the time of PBPC reinfusion were below the toxicity threshold against haemopoietic progenitors. It is concluded that, when adequately supported with PBPCs, NOV can be escalated up to 90 mg m(-2) with acceptable haematological toxicity. PBPCs can be safely reinfused as early as 96 h after NOV administration.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cell Survival; Dose-Response Relationship, Drug; Female; Hematopoiesis; Hematopoietic Stem Cells; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Mitoxantrone

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

The purpose of this study was to evaluate the safety and feasibility of front-line high-dose sequential (HDS) chemotherapy with peripheral blood stem cell (PBSC) transplantation in patients with newly diagnosed high-risk non-Hodgkin's lymphoma (NHL). Thirty-two patients with high-risk NHL (defined by the age-adjusted international index) underwent HDS chemotherapy followed by PBSC transplantation and consolidative radiotherapy. Twenty-eight patients (88%) had intermediate/high grade NHL and four patients (12%) had small noncleaved or lymphoblastic lymphoma. Twenty-four patients were classified as high-intermediate-risk (two risk factors) and eight patients were classified as high-risk (three risk factors). The five phases of HDS (see Fig. 1) consisted of Phase I (adriamycin, vincristine, and prednisone); Phase II (cyclophosphamide, filgrastim [G-CSF], and PBSC harvest); Phase III (methotrexate, leucovorin, vincristine; Phase IV (etoposide, filgrastim [G-CSF]); and Phase V (mitoxantrone, melphalan, autologous peripheral blood stem cell infusion, and filgrastim [G-CSF]). Radiation therapy was given to sites of previous bulk disease, 2400 cGy, (D + 30-100)]. Toxicity, engraftment, hospital utilization, overall survival, and relapse-free survival were evaluated. The high-dose sequential chemotherapeutic regimen was well tolerated. Treatment-related mortality was 6.25% with two deaths occurring secondary to sepsis and one death was caused by progressive disease. The major toxicity in Phase I-IV was grade 3 nausea/vomiting. The major toxicity in Phase V was grade 3 or 4 nausea/vomiting and mucositis. The median follow-up is 18.8 months (range 4-44 months). The overall survival (OS) and relapse-free survival (RFS) at 18 months for all patients were 78% (95% CI 37-90%) and 67% (95% CI 46-88%), respectively. The OS at 18 months for all patients, excluding the four patients with either small noncleaved or lymphoblastic lymphoma, was 82% (95% CI 65-98%) vs. 30% (95% CI 0-86%) (p = 0.0059). One patient in this latter group remains alive at 6 months follow-up. The RFS for all patients, excluding the four patients with either small noncleaved or lymphoblastic lymphoma, was 78% (95% CI 58-97%) vs. 0% (95% CI 0-0%) (p = 0.0004). High-dose sequential chemotherapy with initial PBSC transplantation is well tolerated and appears effective in high-risk NHL. Superior results were noted in patients with intermediate grade versus those with small noncleaved or lymphoblastic NHL.

Topics: Adult; Combined Modality Therapy; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Drug Therapy, Combination; Etoposide; Female; Filgrastim; Follow-Up Studies; Graft Survival; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immunosuppressive Agents; Leucovorin; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Prednisone; Recombinant Proteins; Treatment Outcome; Vincristine

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

It was the objective of our study to evaluate the efficacy of a sequential high-dose therapy with peripheral blood progenitor cell (PBPC) support in patients with low-grade non-Hodgkin's lymphoma (NHL). Since July 1991, 48 patients (23 male/25 female) with a median age of 43 years (range 26-55) were included in the study. At the time of entry, 28 patients were in first and seven in second or higher remission. Twelve patients had relapse of disease and one patient had tumor progression. PBPC were collected during granulocyte colony-stimulating factor (G-CSF)-enhanced leukocyte recovery following treatment with high-dose cytarabine and mitoxantrone (HAM). A median of two leukaphereses (range 2-7) resulted in 6.9 x 10(6) CD34+ cells/kg (median, range 2.1 x 10(6)-38.8 x 10(6)). A comparison was made between the harvests obtained from patients in first remission and those from patients in second remission, in relapse or progressive disease. Patients mobilized in first remission tended to have a greater collection efficiency for CD34+ cells comprising a significantly greater proportion of more primitive CD34+/Thy-1+ progenitor cells. Conversely, leukapheresis (LP) products collected during first remission contained a significantly smaller proportion of CD34+/CD45RA+ cells and CD34+/c-kit+ cells, subsets which reflect a more differentiated progenitor cell stage. Following high-dose therapy and PBPC autografting, the median time to reach platelets > or = 20 x 10(9)/l and neutrophils > or = 0.5 x 10(9)/l and 12 and 13 days, respectively. Two patients died of treatment-related toxic organ failure. Thirty-nine patients are alive in remission after a median follow-up time of 15 months (range 1-31), while seven patients relapsed between 5 and 29 months post-transplantation. Except for one patient autografted in first remission, the patients with relapse had a history of previous relapse or progressive disease. Since the probability of disease-free survival appears to be related to the disease status at the time of autografting, PBPC-supported high-dose therapy including total body irradiation should be investigated further for patients with low-grade NHL while they are in first remission.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Bone Marrow Diseases; Carmustine; Cyclophosphamide; Cytarabine; Disease-Free Survival; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Leukapheresis; Life Tables; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mitoxantrone; Neoplasm Recurrence, Local; Polymerase Chain Reaction; Recombinant Proteins; Remission Induction; Salvage Therapy; Survival Analysis; Transplantation, Autologous; Treatment Outcome; Whole-Body Irradiation

Circulating progenitor cells (CPCs) mobilized from bone marrow will replace the use of bone marrow transplantation because hematopoietic reconstitution is more rapid using the former technique. We report on early and late recovery of hematopoiesis after CPC transplantation in patients with non-Hodgkin's lymphoma (NHL) and analyze the role of variables possibly influencing engraftment. From December 1992 through September 1995, 57 consecutive NHL patients were enrolled in this study. Patients could be divided into 2 groups: the first comprised 32 patients with untreated diffuse large-cell lymphoma and unfavorable prognostic factors; the second comprised 25 patients with resistant or relapsing NHL of low-and high-grade histology. All patients received high-dose chemotherapy (carmustine, cytarabine, etoposide, and melphalan; BEAM) followed by CPC transplantation. In all, 25 patients were treated with granulocyte colony-stimulating factor (G-CSF) after CPC administration. The time to short-and long-term hematologic engraftment and variables correlating with multilineage long-term reconstitution were examined. The time to bilineage (neutrophils and platelets) hematopoietic reconstitution did not differ in G-CSF-treated and-untreated patients. In contrast, the time taken to reach a neutrophil count of 0.5 x 10(9)/1 and a WBC of 1 x 10(9)/1 was significantly shorter in G-CSF-treated patients. Overall, 33 patients achieved long-term, complete trilineage engraftment after a median of 117 days from CPC transplantation. The leukocyte count was the first parameter to reach full engraftment and hemoglobin was the last. According to Kaplan-Meier analysis, 80% of the patients are projected to reconstitute fully at 12 months after transplantation. Univariate and multivariate analyses showed that sustained, long-term hematopoiesis was significantly related to a younger age, an early bilineage reconstitution, and the quantity of CD34+ cells infused.

Topics: Adolescent; Adult; Aged; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Prognosis

To compare the hematologic recovery after high-dose chemotherapy and circulating peripheral-blood progenitor-cell (PBPC) transplant between patients who received recombinant human granulocyte colony-stimulating factor (G-CSF) (treated group) and those who did not (control group).. From December 1992 through June 1994, two sequential and consecutive cohorts of 20 patients each with histologically proven non-Hodgkin's lymphoma (NHL) received high-dose chemotherapy (carmustine [BCNU], cytarabine [Ara-C], etoposide and melphalan [BEAM]) followed by PBPC transplant. The first 20 patients were treated with G-CSF (5 micrograms/kg/d) after PBPC administration. Since the time of platelet and leukocyte recovery in this group was short (< 15 days), with a narrow standard deviation from the mean value, the last 20 patients were not given G-CSF. Hematologic recovery, number of febrile days, rate of documented infections, number of hospital days, duration of gastrointestinal complications, platelet and RBC transfusions, and antibiotic requirements were compared in the two groups.. The two groups of patients were comparable according to disease status, histology, stage, bulky disease bone marrow involvement, elevated lactate dehydrogenase (LDH) level, and median number of infused CD34+ cells and colony-forming units granulocyte-macrophage (CFU-GM). The median time to reach 0.5 x 10(9)/L and 1.0 x 10(9)/L neutrophils was 2 days shorter in G-CSF group, but this difference was not statistically significant. The median times to reach 20 x 10(9)/L and 50 x 10(9)/L platelets were, respectively, 10 and 14 days in the G-CSF group and 11 and 16 days in the control group, but again this was not statistically significant. Moreover, when considering clinically relevant end points including the number of documented infections and antibiotic requirements, platelet transfusions, gastrointestinal toxicity, and days of hospitalization, no differences were demonstrated between the two groups.. Provided an optimal dose of circulating progenitors is infused, NHL patients transplanted with PBPC do not benefit by the administration of hematopoietic growth factors.

Topics: Adult; Antigens, CD; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cohort Studies; Combined Modality Therapy; Cytarabine; Etoposide; Female; Flow Cytometry; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Leukocyte Count; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Platelet Count

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 outcome of patients with relapsed or resistant non-Hodgkin's lymphoma (NHL) undergoing high-dose chemotherapy and autologous bone marrow transplantation (ABMT) and to determine the main prognostic factors.. One hundred seven patients with relapsed or resistant intermediate-/high-grade NHL underwent high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and ABMT at University College Hospitals between September 1981 and February 1993. The minimum follow-up duration of all patients is 6 months.. At 3 months, the overall response rate to BEAM and ABMT was 73% (41% complete response and 32% partial response). The 5-year actuarial overall survival and progression-free survival rates were 41% and 35%, respectively. The early procedure-related mortality rate was 7% (eight of 107 patients). On multivariate analysis, the main prognostic factor was disease status at the time of ABMT. Patients with chemosensitive disease had an actuarial 5-year survival rate of 49% at 5 years compared with 13% for those with chemoresistant disease (P < .001). For patients considered to have chemosensitive disease at the time of transplantation, there is a significant difference in the actuarial progression-free survival rates for those who received high-dose therapy after attaining a partial response to first-line therapy (69% at 5 years) as compared with those with sensitive but relapsed disease (32% at 5 years) (P = .003).. Patients with chemosensitive disease benefit most from high-dose chemotherapy, and those who receive such therapy early after achieving a partial response to first-line therapy have a high rate of cure.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cytarabine; Disease-Free Survival; Etoposide; Female; Follow-Up Studies; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multivariate Analysis; Prognosis; Recurrence; Remission Induction; Survival Rate; Transplantation, Autologous

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

We tested the feasibility and efficacy of a novel high-dose sequential chemoradiotherapy programme (HDS) in 14 relapsed or refractory non-Hodgkin's lymphoma patients with very poor prognostic features, i.e. transformed histology, marrow invasion, low performance status. This regimen included the sequential administration of high-dose cyclophosphamide (CY) 7 g/m2 followed by high-dose methotrexate (MTX) 8 g/m2 and high-dose VP16 2 g/m2 and finally by total body irradiation (TBI)-melphalan and autograft of bone marrow and peripheral blood progenitor cells. No hemopoietic growth factor support was employed in any phase. There was one treatment-related death during the high-dose phase; three other patients did not complete the programme. All 10 patients concluding the programme achieved complete remission, with four patients in complete clinical remission at a median follow up of 34 months. Median overall survival was 27 months and median failure-free survival (FFS) was 12 months. Twenty-six well comparable patients received conventional salvage therapy during the same period. Their projected median overall survival (8 months) and median FFS (4 months) were shorter than in the HDS group (p = 0.06 for overall survival and p = 0.03 for FFS). Thus, HDS is a feasible programme and may offer superior results than conventional therapy in poor-prognosis NHL patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Bone Marrow Transplantation; Cyclophosphamide; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Prognosis; Recurrence; Transplantation, Autologous

Five patients with resistant non-Hodgkin lymphoma (NHL) were given granulocyte-macrophage colony-stimulating factor (GM-CSF, 250 micrograms/m2 daily) after the BEAM pretransplant chemotherapy regimen (carmustine 300 mg/m2, etoposide 1.2 g/m2, cytarabine 800 mg/m2, melphalan 140 mg/m2) because persistent lymphoma cell infiltration of the bone marrow precluded autologous bone-marrow transplantation (BMT). In three patients full haemopoietic reconstitution occurred, with similar kinetics to that seen after autologous BMT. The other two patients died without sustained haemopoietic recovery. GM-CSF may replace autologous BMT in highly selected cases of NHL with progressive disease and bone-marrow involvement.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cytarabine; Drug Evaluation; Etoposide; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Hematopoietic System; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Transplantation, Autologous

Sixteen patients with poor-prognosis acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL) underwent conditioning with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BUCY-2) plus melphalan (90 or 135 mg/m2) and autologous bone marrow transplantation (AuBMT) in a phase I study. At the melphalan dose of 90 mg/m2, grade greater than or equal to 3 regimen-related toxicity (RRT) was observed in five patients (31%; 95% confidence interval [CI], 11% to 59%), with hepatic (venoocclusive disease [VOD]) and urinary (hemorrhagic cystitis) RRT being the most frequent complications. Further escalation of the melphalan dose to 135 mg/m2 was deemed excessively toxic, as three of five patients had grade greater than or equal to 3 RRT. Following this experience, 21 patients with multiple myeloma (MM) and chronic myelogenous leukemia (CML) were treated with BUCY-2 plus melphalan 90 mg/m2 and AuBMT in separate studies. Three of these patients--all with extensively pretreated MM--had grade greater than or equal to 3 RRT (14%; 95% CI, 3% to 36%); no others had grade greater than or equal to 3 RRT. Therefore, a total of eight of the 37 patients (22%; 95% CI, 10% to 38%) who received BUCY-2 plus melphalan 90 mg/m2 conditioning developed grade greater than or equal to 3 RRT; three of these patients (8%; 95% CI, 3% to 25%) died of RRT. Although limited by the relatively small number of patients, our analysis of the patients receiving this regimen showed that the presence of parameters denoting the lymphoid diagnostic group (ie, ALL, NHL, and MM), more extensive pretreatment, and/or more advanced disease status were associated with a higher incidence of grade greater than or equal to 3 RRT. Response data on the AML, ALL, and NHL patients who received BUCY-2 plus melphalan 90 mg/m2 were analyzed: three patients (all with AML in first or second remission) are leukemia-free at 3.0, 2.8, and 1.4 years after AuBMT. The actuarial 2-year event-free survival in this group is 17% (95% CI, 5% to 54%). Response data on the MM and CML patients will be reported subsequently. BUCY-2 plus melphalan at a dose of 90 mg/m2 before AuBMT produces acceptable toxicity in patients who are not heavily pretreated. A full evaluation of the antineoplastic effects of this regimen requires further study.

Topics: Actuarial Analysis; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Busulfan; Combined Modality Therapy; Cyclophosphamide; Drug Evaluation; Female; Humans; Leukemia; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survival Analysis; Transplantation, Autologous

We report the safety and efficacy of 34 consecutive autologous bone marrow transplant (ABMT) procedures performed in adult patients with high-grade lymphoid malignancy after remission induction therapy. Fifteen patients with acute lymphoblastic leukemia (ALL) and six with high-grade non-Hodgkin's lymphoma (NHL) received pretransplant conditioning with intravenous (IV) melphalan and fractionated total body irradiation (TBI). Thirteen other patients with NHL were conditioned with melphalan alone, having previously received local involved field radiotherapy. Unmanipulated noncryopreserved autologous marrow was reinfused within 48 hours of harvesting. Engraftment occurred in all patients with medians of 10 days of neutropenia (neutrophils less than 0.5 x 10(9)/L), 4-day platelet transfusion requirement, 3 U packed RBC transfusion, and 18 days in hospital posttransplant. There were no procedure-related deaths. Actuarial disease-free survival in the 13 patients with ALL receiving autotransplant early in first remission is 48% with a median follow-up of 3 years. Two other ALL patients who had autotransplants after a period of maintenance therapy also remain in complete remission (CR). These results compare favorably with our 34% disease-free survival (DFS) in 15 allogeneic ALL transplant patients and 21% DFS in 19 patients on standard maintenance after a common induction schedule. No relapses have occurred in the 17 NHL patients transplanted in remission (median follow-up 2 years), but the two NHL patients who developed recurrent disease before ABMT died of progressive disease after temporary responses. We conclude that this method of ABMT results in rapid reengraftment with lack of toxicity and that the conditioning treatment used shows good efficacy against disease. It is applicable in high-grade lymphoid malignancy in first remission, and our results call into question the need for marrow purging in ALL and NHL patients transplanted in first remission.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Cryopreservation; Female; Follow-Up Studies; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Mercaptopurine; Methotrexate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Transplantation, Autologous

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

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

Reduced-intensity conditioning and nonmyeloablative conditioning (RIC-NMAC) regimens are frequently used in allogeneic hematopoietic cell transplant (HCT) for non-Hodgkin lymphoma. However, the optimal RIC-NMAC regimen in allogeneic HCT for non-Hodgkin lymphoma is not known.. To investigate whether RIC-NMAC regimens at a higher end of the intensity spectrum are associated with increased nonrelapse mortality and lower overall survival compared with RIC-NMAC regimens at the lower end of the intensity spectrum in patients with non-Hodgkin lymphoma undergoing allogeneic HCT.. This cohort study used data from 1823 adult patients with non-Hodgkin lymphoma in the Center for International Blood and Marrow Transplant Research registry. Included patients underwent allogeneic HCT using matched related or unrelated donors between January 2008 and December 2016. Statistical analysis was performed from June 1, 2019, to February 10, 2020.. Patients received 1 of 4 RIC-NMAC regimens: fludarabine-intravenous busulfan (Flu-Bu), approximately 6.4 mg/kg (n = 458); fludarabine-melphalan (Flu-Mel140), 140 mg/m2 (n = 885); fludarabine-cyclophosphamide (Flu-Cy) (n = 391); or Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI) (n = 89).. The primary outcome was overall survival. Secondary outcomes were nonrelapse mortality, incidence of relapse, progression-free survival, and the incidence of acute and chronic graft-vs-host disease (GVHD).. Of 1823 patients, 1186 (65%) were male, with a mean (SD) age of 54.8 (9.9) years. The 4-year adjusted OS was 58% in the Flu-Bu cohort, 67% in the Flu-Cy-2GyTBI cohort, 49% in the Flu-Mel140 cohort, and 63% in the Flu-Cy cohort (P < .001). After adjustment for age, Karnofsky performance score, HCT comorbidity index, NHL subtype, remission status at HCT, and the use of antithymocyte globulin or alemtuzumab, the regression analysis showed a significantly higher mortality risk associated with Flu-Mel140 compared with Flu-Bu (hazard ratio [HR], 1.34; 95% CI, 1.13-1.59; P < .001). Compared with the Flu-Cy cohort, the Flu-Mel140 cohort had a higher risk of chronic GVHD (HR, 1.38; 95% CI, 1.15-1.65; P < .001). The Flu-Mel140 regimen was associated with a higher nonrelapse mortality risk (HR, 1.78; 95% CI, 1.37-2.31; P < .001) compared with the Flu-Bu regimen.. The findings suggest that use of the more intense RIC-NMAC regimen, Flu-Mel140, may have a negative association with overall survival and may be associated with higher nonrelapse mortality. The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable overall survival.

Topics: Allografts; Busulfan; Cohort Studies; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Lymphoma, Non-Hodgkin; Melphalan; Myeloablative Agonists; Recurrence; Registries; Survival Analysis; Transplantation Conditioning; Vidarabine; Whole-Body Irradiation

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

The DMAC protocol (dexamethasone, melphalan, actinomycin-D, cytarabine) has been evaluated in American studies for the treatment of relapsed canine lymphoma, comparing similarly to other rescue protocols. The aim of this study was to evaluate efficacy and toxicity of DMAC, in a larger UK cohort of resistant canine lymphomas. Medical records of dogs with resistant non-Hodgkin high-grade lymphomas that received DMAC as a rescue protocol were reviewed from 2007 to 2017. Response, time from initiation to discontinuation (TTD) and toxicity (Veterinary Cooperative Oncology Group criteria) were assessed. One hundred dogs were included; 86 received CEOP (modified CHOP including epirubicin) as first-line treatment. Thirty-five dogs (35%) responded: 21 complete responders (CRs) and 14 partial responders (PRs). Responders had significantly longer TTD (P < 0.001) compared with non-responders: 62 days (range 28-952) for CR vs 32 days (range 20-70) for PR. Six CR received more than six cycles of DMAC (range 7-36 cycles) and experienced a longer TTD (median 508, range 126-952 days). Thrombocytopenia occurred in 45% (24 grade 1-2, 21 grade 3-4) and neutropenia in 36% of cases (29 grade 1-2, 7 grade 3-4). Gastrointestinal toxicity occurred in 42% of dogs (40 grade 1-2, 2 grade 3-4). Owing to chemotherapy toxicity, treatment was discontinued in five, and hospitalization required in six cases. In this study, response to DMAC was lower and of generally shorter duration than previously reported. Toxicity was high, but infrequently led to hospitalization or discontinuation of treatment.

Topics: Animals; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Cytarabine; Dactinomycin; Databases, Factual; Dexamethasone; Dog Diseases; Dogs; Female; Kaplan-Meier Estimate; Lymphoma, Non-Hodgkin; Male; Melphalan; Neoplasm Recurrence, Local; Neutropenia; Remission Induction; Schools, Veterinary; Thrombocytopenia; Treatment Outcome; United Kingdom

High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) is an effective salvage therapy for patients with relapsed chemosensitive non-Hodgkin's lymphoma (NHL). However, the optimal conditioning regimen is unclear. Different conditioning regimens prior to AHCT have been used with the two most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide). We sought to compare the two regimens for patients with relapsed NHL undergoing AHCT. We retrospectively compared the outcomes of patients treated with BEAM (N = 269) at The Ohio State University and BUCYVP16 (N = 409) at the Cleveland Clinic followed by AHCT between 2006 and 2014. The primary endpoints were progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR). Patient characteristics between the two groups were similar. After a median follow-up of 3.9 years for BEAM and 4.3 years for BUCYVP16 from AHCT, the rate of relapse (p = 0.69), PFS (p = 0.52), and OS (p = 0.11) were similar between the two conditioning regimens. No differences in survival outcomes were seen in disease subtypes. Multivariable analysis showed significant association toward improved OS with BEAM (HR: 1.56, 95% CI 1.16-2.10) (p < 0.01). Even though the study is limited by its retrospective nature and some differences in cohort, the findings indicate that BEAM could serve as an alternative conditioning regimen prior to AHCT for NHL.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Female; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Retrospective Studies; Stem Cell Transplantation; Transplantation, Autologous; 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

In relapsed or refractory non-Hodgkin lymphoma (NHL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides graft-versus-lymphoma activity resulting in fewer incidences of relapse. However, therapy-related mortality (TRM) remains an important challenge. We attempted to introduce our reduced-intensity conditioning (RIC) regimen. From 2007 to 2013, we treated 28 relapsed or refractory NHLs with allo-HSCT. All were pre-conditioned with fludarabine [FLU, 180 mg/body surface area (BSA)/6 days] and melphalan (MEL, 70 mg/BSA/1 day); 25 (all but 3) were additionally treated with total body irradiation (TBI, 800 cGy/4Fx/2 days). Peripheral blood stem cells were collected from matched siblings (n = 10) or suitably matched unrelated (n = 18) donors. There were eight diffuse large B-cell lymphomas, seven peripheral T-cell lymphoma not otherwise specified, give lymphoblastic lymphomas, two mantle cell lymphomas, and six various other lymphomas. Of these patients, 10 relapsed after auto-HSCT, 5 relapsed after chemotherapy, and 13 were refractory lymphomas. After allo-HSCT, complete remission was achieved in 22 (78.5%) patients. After a median follow-up of 24.8 months, 3-year overall survival and disease-free survival were 62.4 and 59.2% and the 3-year TRM and relapse incidence were 14.9 and 28.6% respectively. Acute and chronic graft-versus-host diseases (GVHDs) were identified in 17 (≥Grade II in 12 patients) and 18 patients respectively, and the group with chronic GVHD showed favourable survival outcomes. In relapsed or refractory NHL, RIC-allo-HSCT using FLU + MEL + 800 cGy TBI showed favourable survival outcomes with acceptable TRM and relapse incidence. Copyright © 2015 John Wiley & Sons, Ltd.

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Disease-Free Survival; Female; Follow-Up Studies; Graft vs Tumor Effect; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Myeloablative Agonists; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine; Whole-Body Irradiation; 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

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

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, CD20; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Follow-Up Studies; France; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Radioimmunotherapy; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Yttrium Radioisotopes

The role of allogeneic stem cell transplantation (SCT) in the management of aggressive non-Hodgkin lymphoma (NHL) remains to be defined, but the number of procedures performed continues to increase. We report here the outcomes of allogeneic SCT using carmustine, etoposide, cytarabine, and melphalan (BEAM)-Campath (Genzyme Corporation, Cambridge, MA) conditioning for aggressive NHL as reported to the British Society of Blood and Marrow Transplantation (BSBMT). This retrospective study identified 46 patients who reported to the BSBMT registry as having undergone BEAM-Campath conditioned allogeneic SCT for aggressive NHL between 1999 and 2010. Disease histology was diffuse large B cell lymphoma (DLBCL, n = 25), DLBCL/Burkitt lymphoma (n = 5), and T cell lymphoma (n = 16). At diagnosis, the median age was 42.5 (range, 17 to 59), 37 had advanced stage disease (Ann Arbor III/IV), 28 had 2 or more extra-nodal sites of disease, and 23 had elevated lactate dehydrogenase. International prognostic index was high or high/intermediate in 58%. The median number of prior therapies was 3 (range, 1 to 5) and 5 patients had previously undergone transplantation (4 autologous, 1 allogeneic). The median age at transplantation was 44.8 (range, 18 to 59), with 34 patients demonstrating chemo-sensitive disease and 22 undergoing transplantation in first response. Performance score was good in 40 patients and all engrafted with a median of 14 days (range, 11 to 27) to neutrophil recovery. At latest follow-up, 20 patients were alive with 17 in complete remission. Acute graft-versus-host disease (GVHD) developed in 7 patients and chronic GVHD developed in 13 (7 limited, 6 extensive). Five patients died from nonrelapse causes, with a cumulative incidence of nonrelapse mortality of 7% at 100 days and 11% at 3 and 5 years. Twenty-one patients died after lymphoma relapse, with a cumulative incidence of relapse/progression of 51% at 1 year and 53% at 5 years. Disease status at transplantation had no impact on relapse rate. Progression-free survival was 41% at 1 year and 36% at 5 years. Overall survival was 54% at 1 year and 42% at 5 years. Overall, BEAM-Campath-conditioned allogeneic SCT is well tolerated and able to deliver durable disease-free survival to a subset of patients with aggressive NHL. However, the high relapse rates indicate further investigation is needed to identify those patients most likely to benefit.

Topics: Adolescent; Adult; Alemtuzumab; Allografts; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Autografts; Bone Marrow Transplantation; Carmustine; Cytarabine; Disease-Free Survival; Female; Follow-Up Studies; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Registries; Societies, Medical; Survival Rate; Transplantation Conditioning; United Kingdom

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

This was an Australasian Bone Marrow Transplant Recipient Registry (ABMTRR)-based retrospective study assessing the outcome of Fludarabine Melphalan (FluMel) reduced-intensity conditioning between 1998 and 2008. Median follow-up was 3.4 years. There were 344 patients with a median age of 54 years (18-68). In all, 234 patients had myeloid malignancies, with AML (n=166) being the commonest indication. There were 110 lymphoid patients with non-hodgkins lymphoma (NHL) (n=64) the main indication. TRM at day 100 was 14% with no significant difference between the groups. OS and disease-free survival (DFS) were similar between myeloid and lymphoid patients (57 and 50% at 3 years, respectively). There was no difference in cumulative incidence of relapse or GVHD between groups. Multivariate analysis revealed four significant adverse risk factors for DFS: donor other than HLA-identical sibling donor, not in remission at transplant, previous autologous transplant and recipient CMV positive. Chronic GVHD was associated with improved DFS in multivariate analysis predominantly due to a marked reduction in relapse (HR:0.44, P=0.003). This study confirms that FluMel provides durable and equivalent remissions in both myeloid and lymphoid malignancies. Disease stage and chronic GVHD remain important determinants of outcome for FluMel allografting.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Australia; Bone Marrow Transplantation; Disease-Free Survival; Female; Follow-Up Studies; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multivariate Analysis; Myeloablative Agonists; New Zealand; Recurrence; Remission Induction; Retrospective Studies; Risk Factors; Transplantation Conditioning; Treatment Outcome; Vidarabine; Young Adult

This sixteenth biannual report of the Cochrane Haematological Malignancies Group highlights recently published randomized controlled trials (RCTs) in the field of hemato-oncology, with special focus on non-Hodgkin's lymphoma. The report covers the publication period June 2012 to July 2013. Trials are selected regarding their methodology and implication for clinical practice. Studies were identified by electronic search of MEDLINE using a broad search filter that covers all topics in hemato-oncology combined with a highly sensitive search filter for randomized trials (Cochrane Handbook for Systematic Reviews of Interventions). Four RCTs are presented in detail, followed by two further RCTs of high importance in a short version. The report is finalized with an overview of new and updated Cochrane Reviews.

Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Boronic Acids; Bortezomib; Carmustine; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Etoposide; Hematologic Neoplasms; Humans; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Melphalan; Nitriles; Nitrogen Mustard Compounds; Prednisone; Primary Myelofibrosis; Pyrazines; Pyrazoles; Pyrimidines; Quality of Life; Randomized Controlled Trials as Topic; Rituximab; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Basal Ganglia; Brain Neoplasms; Child; Cytarabine; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Radiography; Thalamus; Thiotepa; White Matter

At present, accurate assessment of therapeutic efficacy at the early stage of treatment is still a challenge for radiologists. As a new non-radiation whole body imaging technology, Whole body-diffusion weighted imaging (WB-DWI) had shown promising application prospects in therapeutic assessment, which confirmed by many premier animal studies. Here we report that in the chemotherapeutic assessment of malignant non-Hodgkin's lymphoma, WB-DWI can not only detect the morphological change of solid infiltrated lesion as the convention (such as CT, PET, etc.) but also provide information about the growth and decline process of tumor cells in the lesion combining with the dynamic changes of apparent diffusion coefficient (ADC) value, which is sooner than the morphological changes.

Topics: Adult; Aged; Diffusion Magnetic Resonance Imaging; Early Diagnosis; Female; Humans; Immunoglobulin G; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Pilot Projects; Prognosis; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Whole Body Imaging

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

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

Topics: Adult; Busulfan; Female; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Infusions, Intravenous; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Myeloablative Agonists; Thiotepa; Transplantation Conditioning; Transplantation, Autologous

Topics: Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Hematology; Humans; Italy; Lymphoma, Non-Hodgkin; Melphalan; Podophyllotoxin; Practice Guidelines as Topic; Recurrence; Societies, Medical; Time Factors

The optimal preparative regimen for non-Hodgkin's lymphoma patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) is unknown. We compared a total body irradiation (TBI)-based regimen with a chemotherapy-alone regimen.. A retrospective cohort study was performed at a Canadian cancer center. The TBI regimen consisted of cyclophosphamide, etoposide, and TBI 12 Gy in six fractions (CY/E/TBI). The chemotherapy-alone regimen consisted of carmustine, etoposide, cytarabine, and melphalan (BEAM). We compared the acute and long-term toxicities, disease relapse-free survival, and overall survival (OS).. Of 73 patients, 26 received CY/E/TBI and 47 received BEAM. The median follow-up for the CY/E/TBI group was 12.0 years and for the BEAM group was 7.3 years. After PBSCT, no differences in acute toxicity were seen between the two groups. The 5-year disease relapse-free survival rate was 50.0% and 50.7% in the CY/E/TBI and BEAM groups, respectively (p = .808). The 5-year OS rate was 53.9% and 63.8% for the CY/E/TBI and BEAM groups, respectivey (p = .492). The univariate analysis results indicated that patients with Stage IV, with chemotherapy-resistant disease, and who had received PBSCT before 2000 had inferior OS. A three-way categorical analysis revealed that transplantation before 2000, rather than the conditioning regimen, was a more important predictive factor of long-term outcome (p = .034).. A 12-Gy TBI-based conditioning regimen for PBSCT for non-Hodgkin's lymphoma resulted in disease relapse-free survival and OS similar to that after BEAM. PBSCT before 2000, and not the conditioning regimen, was an important predictor of long-term outcomes. TBI was not associated with more acute toxicity or pneumonitis. We found no indication that the TBI regimen was inferior or superior to BEAM.

Topics: Adult; Aged; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Disease-Free Survival; Dose Fractionation, Radiation; Drug Resistance, Neoplasm; Etoposide; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Lymphoma, Non-Hodgkin; Male; Manitoba; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Radiation Pneumonitis; Retrospective Studies; Survival Rate; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Whole-Body Irradiation; Young Adult

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 performed to determine the feasibility of second hematopoietic stem cell transplantation (HSCT) using reduced-intensity conditioning (RIC) with fludarabine and melphalan in patients with relapsed hematologic malignancies after a prior autologous HSCT. Twelve patients (multiple myeloma [n = 7], non-Hodgkin lymphoma [n = 3], and acute myeloid leukemia [n = 2] received allogeneic HSCT using RIC with fludarabine (25 mg/m(2) for 5 days) and melphalan (140 mg/m(2) for 1 day) after a failed autologous HSCT. The graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine plus a minidose of methotrexate. All patients achieved a neutrophil and platelet engraftment in a median 13.5 days and 17.5 days, respectively. The transplant-related mortality was 2 patients (16.7%). Grade II-IV acute GVHD and chronic extensive GVHD were noted in 4 (33.3%) and 1 patient (11.1%), respectively. Over a median follow-up duration of 376 days, 5 patients were alive without evidence of disease. The estimated nonrelapse mortality at 1 year was 28.4%. The estimated overall survival rate at 1 year was 58.3%, and the estimated event-free survival rate at 1 year was 41.7%. Allogeneic HSCT using RIC with fludarabine and melphalan appears to be feasible for a second HSCT in patients with relapsed hematologic malignancies after a failed autologous HSCT.

Topics: Adult; Disease-Free Survival; Feasibility Studies; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Recurrence; Reoperation; Republic of Korea; Retrospective Studies; Salvage Therapy; Survival Rate; Time Factors; Transplantation Chimera; Transplantation Conditioning; Transplantation, Autologous; Treatment Failure; Vidarabine

The Prospective Oral Mucositis Audit was an observational study in 197 patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) undergoing, respectively, high-dose melphalan or BEAM chemotherapy and autologous SCT at 25 European centres. We evaluated the relationship between severe oral mucositis (SOM; WHO Oral Toxicity Scale grade 3-4) and local and systemic clinical sequelae and medical resource use. SOM occurred in 44% of patients. The duration of SOM (mean 5.3 days) correlated with time to neutrophil engraftment. The following parameters increased gradiently with maximum grade of oral mucositis: duration of pain score >or=4, opioid use, dysphagia score >or=4, total parenteral nutrition (TPN) use, incidence and/or duration of fever and infection, and duration of antibiotic use. SOM increased the duration of TPN use by 2.7 days (P<0.001), opioids by 4.6 days (P<0.001), and antibiotics by 2.4 days (P=0.045). SOM prolonged hospital stay by 2.3 days (P=0.013) in MM patients, but not in NHL patients (who tended to have a longer hospital stay). In conclusion, this analysis of prospectively collected observational data provides important insight into the scope and impact of SOM in the European transplant setting.

Topics: Adult; Aged; Analgesics, Opioid; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Humans; Length of Stay; Lymphoma, Non-Hodgkin; Male; Medical Audit; Melphalan; Middle Aged; Multiple Myeloma; Prospective Studies; Risk Factors; Stem Cell Transplantation; Stomatitis; Transplantation Conditioning

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

Autologous hematopoietic stem cell transplantation (AHCT) for relapsed/refractory aggressive non-Hodgkin lymphoma (NHL) results in long-term disease-free survival in 40-50% of patients. The incidence of and risk factors for second cancer development in these patients have not been well studied. We analysed 372 patients with relapsed/refractory aggressive NHL who underwent AHCT from 1987 to 2006. Median age at AHCT was 50 years (range 19-70). Most patients (74%) received two chemotherapy regimens before transplant. High-dose chemotherapy consisted of etoposide and melphalan in 95% of patients and 16% received total body irradiation. Thirty-two patients (9%) developed a second cancer (19 hematologic, 13 solid tumors). The probability of second cancer at 3 and 10 years post-AHCT was 4.4% and 12.9%, respectively. When compared with the general population, the relative-risk of acute myeloid leukemia and new solid tumor was 13.2 (p < 0.0001) and 2.3 (p = 0.0013). Salvage therapy using mini-BEAM was significantly associated with second cancer development (p = 0.004). In conclusion, second cancers are a significant cause of late morbidity and mortality patients treated with AHCT with curative intent, and appear increased in patients exposed to mini-BEAM chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; Neoplasms, Second Primary; Retrospective Studies; Risk Factors; Salvage Therapy; Transplantation, Autologous; 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

High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation is a widely applied treatment for advanced non-Hodgkin lymphoma (NHL), but few studies have analyzed the tolerability and outcomes in older patients compared with younger patients treated in a homogeneous manner. We retrospectively reviewed 152 consecutive patients who underwent autologous stem cell transplantation (ASCT) following BEAM conditioning (carmustine, etoposide, cytarabine, and melphalan) for NHL from January 2000 through August 2004 at our institution. We compared 59 patients age > or =60 years and 93 patients age <60 years. Supportive care was identical for all patients. The frequency of comorbidities was similar between both groups. CD34+ cell doses, days to neutrophil recovery, and days to platelet count >20,000/mm3 were similar in younger and older patients, although days to platelet count >50,000/mm3 were longer in the older patients (median 30.0 days versus 22.5 days, P = .01). Patients over the age of 60 were more likely to develop grade III/IV mucositis than their younger counterparts (37.7% versus17.4%, P = .0063). Otherwise, the frequency of other grade III/IV toxicities were similar between younger and older patients. Treatment-related mortality (TRM) was similar between older and younger patients (8.5% versus 5.4%, P = .45). Although age was not associated with TRM, the Charlson Comorbidity Index Score was significantly correlated with TRM (P = .03). Median disease-free survival was similar between older and younger patients (21.8 months versus 29.9 months, P = .93), as was overall survival (OS) (47.7 months versus 62.5 months, P = .20). After controlling for age, the Charlson Comorbidity Index Score influenced OS [P = .013]. Overall, our cohort of patients with NHL over the age of 60 who underwent ASCT following BEAM conditioning experienced toxicities and survival similar to their younger counterparts. Comorbidities significantly influenced TRM and OS in this retrospective cohort. Future study should focus on improving tolerability of conditioning and careful prospective evaluation of comorbidities and their association with outcomes.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Disease-Free Survival; Female; Graft Survival; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Retrospective Studies; Severity of Illness Index; Stem Cell Transplantation; Transplantation, Autologous

We analysed treatment results of two high-dose regimens: BEAM (carmustine, etoposide, cytarabine, melphalan) and BuMelTT (busulphan, melphalan, thiotepa) in autologous transplant patients with non-Hodgkin lymphoma. Patients received BEAM (n=48) or BuMelTT (n=59) from 1998 to 2005. BEAM group patients were older (mean 59.7 vs 50.1 years), more advanced (stage>or=III 88 vs 61%), had higher IPI/FLIPI scores (score>or=3, 65 vs 19%), and a higher comorbidity index (HCT-CI) (score>or=2, 40 vs 19%). Grade 3-4 complications occurred in 10 patients (17%), with six deaths in the BuMelTT group versus none in the BEAM group. CR was achieved in 20 of 36 (56%) BuMelTT versus 12 of 39 (31%) BEAM patients. After adjusting for IPI/FLIPI, HCT-CI, age and stage of disease, the hazards of death, relapse and treatment failure were similar in both groups. In this retrospective comparison, BEAM regimen appeared to be equally effective but less toxic than BuMelTT.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carmustine; Cytarabine; Drug Evaluation; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Retrospective Studies; Thiotepa; Transplantation, Autologous

The treatment of choice for relapsed/refractory non-Hodgkin's lymphoma (NHL) consists of high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Little is known, however, regarding the comparative toxicity and efficacy of various HDC regimens applied in NHL. We have retrospectively evaluated the clinical aspects of the BCNU, etoposide, cytarabine, and cyclophosphamide (BEAC) and BCNU, etoposide, cytarabine, and melphalan (BEAM) regimens for ASCT. Between April 1994 and February 2005, 97 NHL patients underwent HDC with BEAC (N = 69) or BEAM (N = 28), followed by ASCT, at the Asan Medical Center. We matched each BEAM patient with two BEAC patients having the same International Prognostic Index. Thus, 84 patients (56 BEAC and 28 BEAM) were analyzed. Median age was 40.5 years, and baseline characteristics were well balanced between the two groups. The median time to neutrophil engraftment (>500/mm(3)) was significantly longer with BEAC than with BEAM (12 vs 11 days, P = 0.001), as was the total amount of red blood cell transfusion (6.5 vs 3.7U, P = 0.037), but the median time to platelet engraftment (>20,000/mm(3)) and the total amount of platelet transfusion did not differ between the two groups. BEAM patients had significantly more frequent World Health Organization grade greater than or equal to 2 diarrhea than BEAC patients (46.4 vs 19.6%, P = 0.010), but the incidence of mucositis, nausea/vomiting, and bleeding and the number of episodes of febrile neutropenia and septicemia did not differ between the two groups. Median follow-up for survivors was 33 months in the BEAM group and 89 months in the BEAC group. Median overall survival and median event-free survival were not reached in the BEAM group and were 7.9 (95% confidence interval [CI], 1-14.8 months, P = 0.003) and 3.7 months (95% CI, 0.1-7.2 months, P = 0.001), respectively, in the BEAC group. BEAM appeared to be superior to BEAC for survival. Regimen-related toxicities were similar, except that BEAM was associated with more frequent but acceptable diarrhea.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Retrospective Studies; Survival Rate; Transplantation, Autologous

The Prospective Oral Mucositis Audit assessed the incidence, duration, and determinants of severe oral mucositis (OM; WHO oral toxicity scale grades 3 to 4) in patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) receiving high-dose conditioning chemotherapy before autologous stem-cell transplantation.. Patients with MM (n = 109; mean age, 57 +/- 8 years) or NHL (n = 88; mean age, 50 +/- 13 years) were treated with high-dose melphalan (200 mg/m(2)) or carmustine 300 mg/m(2), etoposide 800 mg/m(2), cytarabine 800 to 1,600 mg/m(2), and melphalan 140 mg/m(2) chemotherapy, respectively, in 25 European centers. OM assessments were made daily until 30 days after transplantation or hospital discharge. High quality of OM assessment was ensured by an intensive training program.. Severe OM occurred in 46% (95% CI, 36% to 56%) of patients with MM and 42% (95% CI, 32% to 53%) of patients with NHL, with a mean duration of 5.3 days (95% CI, 4.4 to 6.1 days) and 5.5 days (95% CI, 4.5 to 6.7 days), respectively. Time from start of conditioning to peak OM score was 12.1 +/- 2.6 and 14.6 +/- 2.4 days. Severe OM risk and/or duration was significantly associated with higher chemotherapy dose per kilogram of body weight and poor performance status, but in contrast with some previous reports, this was not related to age.. Severe OM is more common in the transplantation setting than previously reported, justifying effective preventative and therapeutic measures.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cytarabine; Dose-Response Relationship, Drug; Etoposide; Europe; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Lymphoma, Non-Hodgkin; Male; Medical Audit; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Prospective Studies; Research Design; Risk Assessment; Risk Factors; Stomatitis; Transplantation Conditioning; Transplantation, Autologous

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cecum; Colon; Combined Modality Therapy; Cytarabine; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Tomography, X-Ray Computed; Typhlitis

Although aggressive NHL in relapse after remission can still be cured by second-line treatment followed by high-dose therapy and autologous stem cell transplantation, the long-term prognosis of patients who fail to obtain remission after first-line therapy remains extremely poor. We retrospectively evaluated a series of 29 consecutive patients with primary refractory high-grade NHL who were treated with Dexa-BEAM (DB) as uniform salvage therapy at a single institution. Twenty-nine patients with aggressive NHL primary refractory to CHOP or CHOP-like induction therapy with a median age of 47 (range, 22 - 64) years received 1 - 2 cycles of DB and were candidates for subsequent autologous stem cell (PBSC) mobilization and transplantation (PBSCT). Follow-up of all patients was updated in March 2004. Eight of 29 patients (28%) responded to one cycle of DB (1 complete/7 partial remissions); 2 of whom are alive after PBSCT (1 autologous/1 matched unrelated donor), 1 patient died after autologous PBSCT. Reasons for failure to proceed to high-dose therapy in spite of response to DB were recurrent progressive disease (n = 2), septicemia (n = 1), and allogeneic transplant-related mortality after mobilization failure to DB (n = 2). Twenty-one patients failed to respond to DB and died of progressive disease. Overall survival was 7% after 41 months. We conclude that Dexa-BEAM salvage therapy is not effective in patients with truly primary refractory high-grade NHL. The efficiency of rituximab combined with Dexa-BEAM or novel chemotherapeutic strategies needs to be established.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Dexamethasone; Etoposide; Female; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Salvage Therapy; Survival Rate; Transplantation, Autologous

The incidence of mucositis caused by autologous hematopoietic stem cell transplantation (AHSCT) is relatively high. The severe painful mucositis can reduce the quality of life of patients obviously. Transdermal fentanyl is efficient in treating chronic pain of cancer, and also can relieve the severe pain of mucositis resulted from chemotherapy. This study was to investigate the efficacy and safety of transdermal fentanyl for the severe painful mucositis caused by AHSCT.. A total of 22 malignant tumor patients suffered from severe mucositis caused by high dose chemotherapy combined AHSCT. The analgesic degree before and after treatment was evaluated by the scores of Visual Analogue Scale (VAS) (range 0-10). The median VAS scores of all patients were above 4 (moderate to severe pain) before the administration of transdermal fentanyl. The quality of life before and after treatment was evaluated by the Standard of Quality of Life drew up in China in 1990. The adverse events after treatment were evaluated by Common Toxicity Criteria formulated by National Cancer Institute of the USA.. The median VAS score has been decreased from baseline at 6 (4-9) to 3.5 (0-9) on Day 3, 2 (0-6) on Day 5, 0.5 (0-8) on Day 7, 0 (0-6) on Day 10, and 0 (0-5) on Day 15 after treatment (P<0.001). The overall response rate was 100%, while the complete response rate was 45.5%. The quality of life of the patients was improved significantly (P<0.01). The adverse events after treatment of transdermal fentanyl included dizziness, somnolence, dysuria, mild and transient nausea, vomiting, discomfort of stomach, and so on. All the adverse events disappeared within several days after proper managements. Neither severe adverse event nor drug addiction was found.. Transdermal fentanyl has good analgesic effect on painful severe mucositis induced by AHSCT. It is convenient and well tolerated, and could improve quality of life significantly.

Topics: Administration, Cutaneous; Adolescent; Adult; Analgesics, Opioid; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Female; Fentanyl; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mucositis; Pain; Pain Measurement; Podophyllotoxin; Quality of Life; Transplantation, Homologous; Young Adult

High-dose chemotherapy with allogeneic stem cell transplantation (SCT) has proven to be a successful treatment for low-grade lymphoma (LGL), but is associated with considerable transplant-related mortality (TRM). In an effort to reduce toxic mortality while maintaining the graft-versus-leukemia effect, allogeneic SCT has been combined with a reduced-intensity conditioning (RIC) regimen. The aim of this study was to determine the outcome of patients with LGL treated with RIC allogeneic SCT.. This retrospective multicenter study included 73 patients with relapsed or refractory LGL allografted after a RIC regimen between 1998 and 2005 whose data were recorded in a French registry.. Patients received a median of three lines of therapy prior to RIC allogeneic SCT. The most widely used conditioning regimens were fludarabine + busulfan + antithymocyte globulin (n=43) and fludarabine + total body irradiation (n=21). Prior to allografting, patients were in complete response (CR; n=21), partial response (PR; n=33) or had chemoresistant disease (n=19). The median follow-up was 37 months (range, 16 to 77 months). In patients in CR, PR and chemoresistant disease, the 3-year overall survival rates were 66%, 64% and 32%, respectively, while the 3-year event-free survival rates were 66%, 52% and 32%, respectively. The 3-year cumulative incidences of TRM were 32%, 28% and 63%, respectively. The incidence of relapse was 9.6%.. Although associated with significant TRM, RIC allogeneic SCT in advanced chemosensitive disease leads to long-term survival.

Topics: Adult; Aged; Antibodies, Monoclonal; Antilymphocyte Serum; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Data Collection; Disease-Free Survival; Etoposide; Female; France; Graft vs Host Disease; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Proportional Hazards Models; Remission Induction; Retrospective Studies; Salvage Therapy; Survival Analysis; Survival Rate; T-Lymphocytes; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine; Whole-Body Irradiation

Melphalan is widely used in the treatment of multiple myeloma. Pharmacokinetics of this alkylating drug shows high inter-individual variability. As melphalan is a phenylalanine derivative, the pharmacokinetic variability may be determined by genetic polymorphisms in the L-type amino acid transporters LAT1 (SLC7A5) and LAT2 (SLC7A8).. Pharmacokinetics were analysed in 64 patients after first administration of intravenous melphalan. Severity of side effects was documented according to WHO criteria. Genomic DNA was analysed for polymorphisms in LAT1 and LAT2 by sequencing of the entire coding region, intron-exon boundaries and 2 kb upstream promoter region. Selected polymorphisms in the common heavy chain of both transporters, the protein 4F2hc (SLC3A2), were analysed by single nucleotide primer extension.. Melphalan pharmacokinetics was highly variable with up to 6.2-fold differences in total clearance. A total of 44 polymorphisms were identified in LAT1 and 21 polymorphisms in LAT2. From all variants, only five were in the coding region and only one heterozygous non-synonymous polymorphism (Ala94Thr) was found in LAT2. Numerous polymorphisms were found in the LAT1 and LAT2 5'-flanking regions but did not correlate with expression of the respective genes. No significant correlations could be observed between the polymorphisms in 4F2hc, LAT1, and LAT2 with melphalan pharmacokinetics or with melphalan side effects.. The study confirmed that these transporter genes are highly conserved, particularly in the coding sequences. Genetic variation in 4F2hc, LAT1, and LAT2 does not appear to be a major cause of inter-individual variability in pharmacokinetics and of adverse reactions to melphalan.

Topics: Amino Acid Substitution; Amino Acid Transport System y+; Antineoplastic Agents, Alkylating; Base Sequence; DNA Primers; Exons; Fusion Regulatory Protein 1, Heavy Chain; Fusion Regulatory Protein 1, Light Chains; Genetic Variation; Heterozygote; Humans; Introns; Large Neutral Amino Acid-Transporter 1; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Pharmacogenetics; Polymorphism, Genetic; Promoter Regions, Genetic; RNA, Messenger; RNA, Neoplasm

We retrospectively evaluated early and long-term complications of an intensified conditioning regimen consisting of busulfan and etoposide in combination with either nimustine hydrochloride (ACNU) (BVA regimen, n = 18) or melphalan (BVL regimen, n = 34) in 52 children with acute leukemia or non-Hodgkin's lymphoma. With a median follow-up of 13.2 years after the BVA regimen and 8.1 years after the BVL regimen, 61% and 76% of patients, respectively, are in continuous complete remission. Transplantation-related mortality was 17% and 6% after the BVA and BVL regimens, respectively, and the corresponding relapse rates were 17% and 15%. The most common and severe toxicity was pulmonary complication in the BVA regimen, which was seen in 67% of patients and was life-threatening in 20%. Thirty-three percent of patients after the BVA regimen and 24% after BVL died of relapse or disease progression (n = 9), interstitial pneumonia (n = 2), fungal pneumonia (n = 1), or chronic graft-versus-host disease (n = 2). One of the long-term survivors developed secondary leukemia. A significant decrease in the height standard deviation score of more than 2 SD from diagnosis to the last follow-up was seen in 17% of the patients, with hypothyroidism in 15%, and alopecia in 42%. Because our experience is limited to a small heterogeneous population of patients who mainly underwent transplantation in the first remission, we cannot draw conclusions on the treatment's effectiveness. The BVL regimen is tolerable, however, because no regimen-related death was observed, whereas the BVA regimen is not recommended because of the high incidence of pulmonary complications. The effectiveness of the BVL regimen requires further study.

Topics: Acute Disease; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Child; Child, Preschool; Disease-Free Survival; Etoposide; Female; Follow-Up Studies; Humans; Infant; Leukemia; Lymphoma; Lymphoma, Non-Hodgkin; Male; Melphalan; Nimustine; Recurrence; Retrospective Studies; Stem Cell Transplantation; Survival Rate; Transplantation Conditioning; Transplantation, Homologous

A 56-year-old married female presented in May 1998 with a 5-month history of xanthelasma of the eyelids, followed 4 months later by two enlarged lymph nodes of the left side of the neck and three of the left axilla. At the same time, she developed xanthomatous patches on the face, neck, and shoulders (Fig. 1). The cutaneous lesions were xanthomatous nodules and plaques, affecting the periorbital regions. Later, the whole face was affected, followed by ulcerated lesions on the scalp, chest, back, and extremities (Fig. 2). The skin lesions became painful, pruritic, ulcerated tumors (Fig. 3). In July 1998, computed tomography (CT) scans of the chest and abdomen with contrast medium showed pretracheal, bilateral axillary, right retrochural, paracaval, aortocaval, and para-aortic lymph node enlargement. These findings were suggestive of lymphoma. CT scan also showed slight heterogeneous hypodensity in the upper part of the right lobe of the liver, suggesting fatty infiltration. The spleen, pancreas, and suprarenal glands appeared normal. One cervical and two left axillary lymph nodes were excised. They revealed total replacement of the nodular architecture by a diffuse proliferation of mature lymphoid cells having small nuclei and a crumbled chromatin pattern, and very rare mitosis. It was concluded from the lymph node biopsies that these changes were typical of non-Hodgkin's lymphoma, diffuse and small cell type, of low-grade malignancy. A bone marrow aspirate showed a marrow heavily infiltrated by lymphoid cells with some immaturity. The megakaryopoiesis was adequate. Trephine biopsies showed similar changes. Iron stores appeared to be absent. The bone marrow picture was consistent with diffuse, well-differentiated non-Hodgkin's lymphoma, developing into chronic lymphocytic leukemia (CLL). Endoscopy showed antral-type gastric mucosa exhibiting mild chronic gastritis. Skin biopsy from a fresh lesion on the back showed a diffuse inflammatory cell infiltrate with collections of histiocytic cells. It also showed necrobiotic foci, surrounded by mixed inflammatory cells, dark palisaded foamy histiocytes, and a few Touton giant cells. These findings are compatible with necrobiotic xanthogranuloma (NXG) (Figs 4 and 5). Blood film showed normochromic, normocytic erythrocytes with anisopoikilocytotic leukocytes and normal platelets. The sedimentation rate was 90 mm in the first hour. The blood picture also showed monoclonal IgG paraprotein (3170 mg/dL) of the kappa li

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Chlorambucil; Cyclophosphamide; Female; Glucocorticoids; Granuloma; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; Necrobiotic Disorders; Paraproteinemias; Skin Diseases; Treatment Failure; Treatment Outcome; Xanthomatosis

Reduced-intensity regimens (RIRs) are being used with increasing frequency in patients with non-Hodgkin's lymphoma (NHL) undergoing allogeneic transplantation. The impact of dose reduction on relapse and survival has not been extensively studied. We performed a retrospective analysis of 88 patients conditioned with conventional myeloablative regimens (CMRs) (n = 48) and an RIR (n = 40) of fludarabine 125 mg/m(2) and melphalan 140 mg/m(2). Compared with the patients receiving CMR, those receiving RIR were older, had more often failed autologous transplantation, and had more frequently received peripheral blood and unrelated donor transplants. Graft-versus-host disease prophylaxis was provided with cyclosporine + methotrexate +/- prednisone for the CMR and with cyclosporine + mycophenolate +/- methotrexate for the RIR. The relapse rate was significantly lower in the patients receiving CMR than in those receiving RIR (13% vs 28%; P = .05). The 1-year transplantation-related mortality rate was 33% for CMR and 28% for RIR (P = .40). Kaplan-Meier 2-year overall survival and progression-free survival were 52% and 46% for CMR versus 53% and 40% for RIR (P = not significant). Using cumulative incidence functions based on competing risks, univariate analysis, and treatment-related prognostic factors, we found that higher treatment intensity (P = .03; relative risk [RR] = 35%) and absence of previous autologous transplantation (P = .0007; RR = 20%) were associated with a lower relapse rate. Using a Cox univariate proportional hazards model, we found that chemosensitive disease at transplantation (P = .05; RR = 57%) and absence of previous autologous transplantation (P = .002; RR = 37%) were associated with improved survival. Our observation of similar survival in the patients receiving CMR and those receiving RIR confirms that RIRs are feasible alternatives for high-risk patients with NHL; however, the data suggest that reduced treatment intensity and previous autologous transplantation are associated with increased relapse.

Topics: Adolescent; Adult; Aged; Busulfan; Cause of Death; Cohort Studies; Cyclophosphamide; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Graft vs Host Disease; Hepatic Veno-Occlusive Disease; Humans; Infections; Kaplan-Meier Estimate; Lung Diseases, Interstitial; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Proportional Hazards Models; Reoperation; Retrospective Studies; Risk Factors; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine; Whole-Body Irradiation

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

High-dose therapy (HDT) is now recommended for patients under 60 years of age with chemosensitive relapsed aggressive non-Hodgkin's lymphoma. However, approximately half of these patients will be cured by HDT. Prognostic factors are needed to predict which patients with chemosensitive lymphoma to second-line therapy could benefit from HDT. We retrospectively investigated the prognostic value of the widely used age-adjusted International Prognostic Index (AA-IPI) calculated at the time of relapse (35 patients) or just before second-line salvage therapy for primary refractory disease (5 patients). The median age was 51 years (range 18-64 years). Thirty-six patients had diffuse large B-cell lymphoma. Salvage cytoreductive therapy before HDT was DHAP/ESHAP (cytarabine, cysplatin, etoposide, steroids) in 17 patients, VIM3-Ara-c/MAMI (high-dose cytarabine, ifosfamide, methyl-gag, amsacrine) in 17 patients, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or reinforced CHOP in 4 patients, high-dose cyclophosphamide and etoposide in 2 patients. The HDT regimen consisted of BEAM (carmusine, cytarabine, etoposide, melphalan) in all cases. Eleven patients were in partial remission and 29 in complete remission at the time of HDT. Ten patients had an IPI >1, 16 had relapsed early (<6 months after first-line therapy) or disease was refractory to first-line therapy (5 of the 16 patients). The median follow-up was 6.07 years (range 1.24-9.74 years). Overall survival was not statistically different in patients with refractory disease or in those who relapsed early compared with late failures (>6 months after first-line chemotherapy) (P=1), but the AA-IPI >1 was associated with a poor outcome (P=0.03). In conclusion, the AA-IPI could have a prognostic value in patients with chemosensitive recurrent lymphoma treated with BEAM HDT.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Medical Oncology; Melphalan; Middle Aged; Prednisolone; Prognosis; Recurrence; Remission Induction; Stem Cell Transplantation; Transplantation, Autologous; Vincristine

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

High-dose intensification and autologous stem-cell transplantation (ASCT) is widely used to consolidate patients with non-Hodgkin's lymphoma (NHL), who have reached a stage of minimal residual disease. However, patients with persisting marrow and/or blood involvement and those who fail peripheral blood hemopoietic progenitor mobilization are excluded from ASCT. For such patients with no available graft to infuse, we developed 15 years ago, before the anti-CD20 monoclonal antibody therapeutic era, the use of the BEAM pretransplant regimen followed only by the administration of three cytokines (erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor). We report here on the long-term follow-up of 33 patients treated with this approach. In all, 33 NHL patients underwent the BEAM (carmustine, VP-16, cytosine-arabinoside, melphalan) followed by the administration of the three cytokines from January 1994-2000. A backup marrow, albeit infiltrated by tumor cells, had been collected earlier and stored in all. A total of 30 patients (91%) recovered normal hematopoiesis. In total, 32 patients (97%) recovered neutrophils (>500/microl) at a median of 19 days and 30 patients (91%) recovered platelets (>20,000/microl) at a median of 26 days. Age, richness of backup graft and blood-hemoglobin level at intensification had an impact on the time for hematopoietic recovery (P=0.014, P=0.014, P=0.048). The median follow-up was 62 months. Five patients died from toxicity related to the procedure. Eight patients relapsed and died. A total of 20 patients (61%) are alive, 16 (49%) in complete remission. A 5-year disease-free survival was 52+/-9%, relapse incidence 35+/-16%, mortality due to the procedure 12+/-12% and overall survival 61+/-10%. The BEAM regimen is not myeloablative. The BEAM+3CK procedure is a feasible therapeutic option that has shown efficacy in poor risk NHL patients who were not eligible for autografting because of persisting marrow/blood tumor contamination, or poor hemopoietic progenitor harvesting. It is unclear today whether some of these patients would have cleared their marrow/peripheral blood with the additional use of anti-CD20 treatment, thereby making the classical approach (BEAM followed by the infusion of a clean autograft) feasible.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Drug Therapy, Combination; Erythropoietin; Etoposide; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Survival Rate; Time Factors

The purpose of this evaluation was to investigate the efficacy of high-dose chemotherapy with thiotepa, melphalan, and carboplatin (TMCb), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 42 patients, 23 with intermediate-grade NHL and 19 with HD, received thiotepa (500 mg/m2), melphalan (100 mg/m2), and carboplatin (1050-1350 mg/m2) followed by autologous PBSC infusion. Of 21 patients with more advanced disease, four had primary refractory disease, one was in complete remission (CR)-2, 11 were in first refractory relapse, and five were beyond first relapse. Of 21 patients with less advanced disease, two were in CR-1, four were in CR-2, and 15 were in first responding relapse. In all, 14 patients (33%) had received prior radiotherapy prohibiting a total-body irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival (EFS), and relapse for all patients were 0.65, 0.60, and 0.21 (0.85, 0.80, and 0.10 for patients with less advanced disease and 0.47, 0.42, and 0.33 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.12. Grade 3-4 regimen-related toxicities (RRT) occurred in five of 42 (12%) patients and death due to grade-4 RRT occurred in only one (2.5%) patient. These preliminary data suggest that 0.42% EFS in this study for advanced disease patients is highly encouraging and high-dose TMCb followed by autologous PBSC transplantation is well tolerated as well as an effective regimen in patients with intermediate-grade NHL or HD, and may be comparable to some previously used regimens including TBI-based regimens.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Combined Modality Therapy; Female; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Retrospective Studies; Stem Cell Transplantation; Survival Analysis; Thiotepa; Transplantation, Autologous; Treatment Outcome

The long-term survival of patients with non-Hodgkin's lymphoma after conventional chemotherapy is about 35%, with the remaining 65% of patients tending to be refractory or experience relapse. As such, primary refractory patients responding to salvage chemotherapy, and sensitive relapsed patients and primary high-risk patients are recommended to receive high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplantation (PBSCT). We evaluated the role of HDC and autologous PBSCT in patients with primary refractory, primary high risk, and sensitive relapsed non-Hodgkin's lymphoma.. We performed a retrospective analysis of the data from 50 patients with non-Hodgkin's lymphoma who were treated with HDC and autologous PBSCT in the Catholic Hematopoietic Stem Cell Transplantation Center between 1997 and 2002.. Of the 50 patients, the conditioning regimen was BEAM in 20, CMT (cyclophosphamide, melphalan and thiotepa) in 19, fludarabine- and total body irradiation (TBI)-based regimen in 8, and cyclophosphamide and TBI in 2. There were 3 (6%) deaths due to treatment-related toxicity within the first 50 days after transplantation. Twenty-five patients remain alive at a median follow-up duration of 40.5 months (range 9-61). Among the patients with partial response before transplantation, 76% showed further response after transplantation. In half of these responders, the disease state was changed into complete response (CR) after transplantation. 2-year overall survival was 52% and 2-year progression free survival was 36.8%. Median overall survival was 34 months (range 8-60), and median progression-free survival was 8 months (range 1-14). Median overall survival was 14 months (range 9-19) in the primary high-risk group (n=13), 7 months (range 4-10) in the resistance relapse group (n=5), and 6 months (range 0-14) in the primary refractory group (n=10). Overall survival in the sensitive relapse group (n=22) did not reach the median; the mean overall survival in this group was 33 months. The disease status before transplantation was the only significant prognostic factor in determining overall survival (p=0.032) and progression- free survival (p=0.001).. HDC and autologous PBSCT appears to produce high response rate. Primary high-risk group and sensitive relapse group had good prognosis, while refractory and resistance relapse group had poor prognosis. And the pre-transplantation disease status was the only significant prognostic factor in multivariate analysis.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Stem Cell Transplantation; Survival Analysis; Thiotepa; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vidarabine; Whole-Body Irradiation

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

Since it exerts a stronger antitumor action than predinisolone, dexamethasone was used for therapy of patients with non-Hodgkin's lymphoma refractory to CHOP. All patients (66), resistant to CHOP, suffered bone marrow involvement. Dexamethasone pulsed therapy was given to 45 patients, with 21 COP-BLAM or ASHAP, MAD, Dexa-BEAM treated in control. Median response duration in high- and low-grade non-Hodgkin's lymphoma groups was 2 and 12 months, respectively.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Dexamethasone; Etoposide; Humans; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; 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

To assess the safety and efficacy of intensive methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma (PCNSL).. Twenty-eight patients received induction chemotherapy using high-dose systemic methotrexate (3.5 g/m2) and cytarabine (3 g/m2 daily for 2 days). Fourteen patients with chemosensitive disease evident on neuroimaging then received high-dose therapy using carmustine, etoposide, cytarabine, and melphalan with autologous stem-cell rescue.. The objective response rate to the induction-phase chemotherapy was 57%, and median overall survival is not yet assessable, with a median follow-up time of 28 months. The overall median event-free survival time is 5.6 months for all patients and 9.3 months for 14 patients who underwent transplantation. Six of these 14 patients (43%) remained disease-free at last follow-up. Treatment was well tolerated; there was one transplantation-related death. Prospective neuropsychologic evaluations have revealed no evidence of treatment-related neurotoxicity.. This treatment approach is feasible in patients with newly diagnosed PCNSL without evidence of significant related neurotoxicity. Although the transplantation results are similar to those achieved in patients with aggressive or poor-prognosis systemic lymphoma, the low response rate to induction chemotherapy and the significant number of patients who experienced relapse soon after HDT suggest that more aggressive induction chemotherapy may be warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Central Nervous System Neoplasms; Combined Modality Therapy; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Remission Induction; Safety; Salvage Therapy; Survival Rate; Transplantation, Autologous; Treatment Outcome

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

Mixed chimerism after allogeneic bone marrow transplantation has been shown to cure a number of genetic disorders in both the clinical and experimental settings. Although encouraging results have been reported from animal experiments, the role of mixed chimerism in eliminating autoimmune disorders is not clear.. A 50-year-old man with extensive psoriasis received an allogeneic transplant from his brother after nonmyeloablative conditioning with fludarabine, melphalan, and Campath-1H for relapsed non-Hodgkin's lymphoma. The chimerism status and the immunological recovery after the transplant were serially monitored.. Twenty-one months after the transplant, the patient continues to be in complete remission from psoriasis and lymphoma with stable mixed chimerism (30% to 40% donor cells), despite significant recovery of T-cell subsets and antigen-specific response.. If mixed chimerism can be achieved safely with novel low-intensity conditioning regimens and results in sustained remission of autoimmune diseases, allogeneic transplantation may become a realistic therapy in the management of some patients with autoimmune disease.

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclosporine; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Lenograstim; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Nuclear Family; Psoriasis; Recombinant Proteins; T-Lymphocyte Subsets; Transplantation Chimera; Vidarabine

High relapse rates during the first year after autologous stem cell transplantation (ASCT) for multiple myeloma or non-Hodgkin lymphoma are due to the failure of high-dose chemotherapy to eradicate minimal residual disease. Post-ASCT immunorecovery studies have shown that quantities of natural killer (NK) cells return to normal within 1 month post-ASCT in contrast to the recovery of T and B cell populations (up to 1 year). Preclinical studies have demonstrated that NK cells have potent antitumor activity. IL-2 and IFN-alpha enhance NK-cell activity. We investigated the efficacy of IL-2 and IFN-alpha to up-regulate NK-cell cytotoxicity at 14 days post ASCT. Twenty patients undergoing ASCT had PBMCs collected pretransplantation and at 14 days post transplantation. PBMCs (effector cells) from each blood sample were incubated in vitro with IFN-alpha and IL-2 at 10000 IU/ml. NK cell activity was determined by sodium chromate (51)Cr release assay for lysis of K562 target cells. IL-2 and IFN-alpha each increased lysis of K562 cells compared with placebo (effector-to-target ratio, 50:1, P < 0.001). Increased NK cell activity occurred in samples from all patients. IL-2 and IFN-alpha up-regulated NK cell activity at 14 days post ASCT. They may be useful as immunomodulators as early as 14 days post ASCT to eradicate or control minimal residual disease.

Topics: Adjuvants, Immunologic; Adult; Aged; Alkylating Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cells, Cultured; Cytarabine; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunophenotyping; Interferon-alpha; Interleukin-2; K562 Cells; Killer Cells, Natural; Lymphocyte Count; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multiple Myeloma; Podophyllotoxin; Time Factors; Transplantation Conditioning; Transplantation, Autologous

Long-term outcome, after first line intensified high-dose sequential (i-HDS) chemotherapy, was evaluated in 46 patients, aged < or =65 years, with advanced low-grade lymphoma. Seventeen patients had small lymphocytic lymphoma (SLL), 29 had follicular lymphoma (FL), 10 of them with histologic transformation. I-HDS included: (1) tumor debulking, by 2 APO+2 DHAP courses; (2) sequential administration of high-dose (hd) etoposide, methotrexate, and cyclophosphamide, followed by peripheral blood progenitor cell (PBPC) harvest; (3) hd-mitoxantrone + melphalan with PBPC autograft. Ten FL patients had their PBPC immunologically purged ex vivo. There were two treatment-related deaths; five FL patients had short-lasting response followed by disease progression, five SLL reached a stable PR; overall, 34 patients (74%) reached CR. At a median follow-up of 4.3 years, the estimated 9-year OS and EFS were 84% and 45%, respectively. No significant differences were observed in the OS among patients at low, intermediate or high IPI score, with an estimated OS projection of 95%, 78%, and 75%, respectively. FL had longer survival without evidence of residual disease (9-year EFS: 59%) as compared to SLL patients (8.8-year EFS: 17%); however, both groups had prolonged survival and no need of salvage treatment, as shown by the time to disease progression curve, projected to 66% and 62% for SLL and FL, respectively. The results indicate that hd-approach in low-grade lymphoma: (1) is associated with longer progression-free survival as compared to conventional therapies; (2) may imply higher tumor mass reduction in FL as compared to SLL patients; (3) offers long life expectancy, with potential survival benefits at least for patients at intermediate/high IPI score.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Disease Progression; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Etoposide; Feasibility Studies; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Mitoxantrone; Remission Induction; Survival Analysis; Treatment Outcome; Vincristine

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

The occurrence of acute leukaemia and other secondary neoplasms in 432 patients treated with conventional chemotherapy for multiple myeloma was analysed after a follow-up period of 11-19 yr (mean 16 yr). The number and organ-specific distribution of observed solid neoplasms was close to that expected in the general population. Non-Hodgkin's lymphoma developed in three patients (expected 0.7, p = 0.19). Acute leukaemia was diagnosed in 14 patients with an actuarial risk of 9.8% at 9 yr. No further cases were diagnosed thereafter. The average numbers of courses (26.2 vs. 25.5) and cumulative doses of melphalan (1440 and 1400 mg) were similar in patients with or without acute leukaemia. It seems possible that the advanced stage of multiple myeloma is more vulnerable to the leukaemogenic effect of melphalan compared with the earlier stages.

Topics: Acute Disease; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Finland; Follow-Up Studies; Humans; Leukemia; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Staging; Neoplasms, Second Primary; Organ Specificity

Limited data are available concerning feasibility and toxicity of progenitor cell mobilization and high-dose therapy (HDT) supported by peripheral blood stem cell transplantation (PBSCT) in elderly patients (>/=60 years) with non-Hodgkin's lymphoma (NHL). From 1995 to 1999, 17 elderly NHL patients (median age 63 years, range 60-70) entered our HDT program and were mobilized with CY (4 g/m2) followed by G-CSF. Mobilization was successful in 13 patients, who then received BEAM or BEAC followed by PBSCT. The feasibility and toxicity of progenitor cell mobilization and HDT in the elderly patients were compared with experiences in 62 NHL patients <60 years (median 46 years, range 16-59), who received the same mobilization protocol and of whom 48 patients received HDT supported by PBSCT. No significant differences were observed between these groups in the success rate of progenitor cell mobilization, in the number of CD34-positive cells collected or in the number of aphereses needed. HDT appeared to be somewhat more toxic in the elderly patients: a higher peak CRP value (P = 0.08) and longer in-hospital stay (P = 0. 05) were observed. No differences were found in transplant-related mortality or severe organ toxicity between these age groups except for oral mucositis grade >2, which tended to be more common in the elderly patients (P = 0.07). We conclude that progenitor cell mobilization and HDT supported by PBSCT is also feasible in selected elderly patients with NHL. Bone Marrow Transplantation (2000) 26, 737-741.

Topics: Adolescent; Adult; Age Factors; Aged; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Disease Progression; Etoposide; Female; Graft Survival; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Infections; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Survival Rate; Time Factors; Transplantation Conditioning

We conducted a pilot study in 20 patients with high-risk or recurrent/refractory non-Hodgkin's lymphoma (NHL) using high-dose sequential chemotherapy (HDSC) and autologous hematopoietic cell transplantation (AHCT). After cytoreduction with standard salvage therapy, HDSC/AHCT was administered in 4 phases at 2- to 4-week intervals. Phase 1 consisted of cyclophosphamide 7 g/m2 followed by granulocyte colony-stimulating factor (G-CSF) at 10 microg/kg per day and leukapheresis upon recovery from white blood cell nadir. The hematopoietic cell product was enriched by Percoll gradient separation and purged with a B-cell or T-cell monoclonal antibody panel and complement. Phase 2 consisted of methotrexate 8 g/m2 with leucovorin rescue and vincristine 1.4 mg/m2. Phase 3 was etoposide 2 g/m2 with G-CSF 5 microg/kg per day. In phase 4, the preparative regimen of mitoxantrone 60 mg/m2 and melphalan 180 mg/m2 was administered followed by AHCT. The NHL histologies were diffuse large cell, follicular/diffuse mixed, small noncleaved cell, T-cell-rich B-cell, lymphoblastic, and peripheral T cell. The remission status was first partial remission (PR1; n = 1) or beyond first complete remission (post-CR1; n = 19). Of the 20 patients enrolled, 11 proceeded through all 4 phases. Nine were removed from the study after the first or second phase because of progressive disease (n = 5), poor hematopoietic cell mobilization (n = 1), excessive toxicity (n = 2), and chronic active hepatitis C (n = 1). Treatment-related toxicities in the remaining 11 transplant recipients were cardiomyopathy, hemorrhagic cystitis, persistent cytopenias, acute renal failure, abnormal liver function test results, and infectious complications. There were no treatment-related deaths. Eight of the 11 transplant recipients were alive, 6 without disease, at a median follow-up of 2.7 years. The estimated median 2-year event-free survival was 55%, and overall survival was 70%. We conclude that HDSC/AHCT in refractory/recurrent NHL is associated with considerable acute and chronic toxicities. Given the toxicity profile, efficacy data were not sufficiently promising to warrant further study.

Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Purging; Cardiomyopathies; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Cyclophosphamide; Cystitis; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Etoposide; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Infections; Leucovorin; Life Tables; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Mitoxantrone; Pilot Projects; Salvage Therapy; Survival Analysis; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vincristine

We observed an unexpectedly rapid rise in platelet counts with complete haematological recovery after a BEAM regimen, in a patient who could not be rescued by autologous transplant but who received filgrastim, epoetin alfa, and ancestim. We feel that these results may be attributed to this specific growth factor combination, including ancestim, a cytokine known to act on primitive stem cells. If confirmed, this observation may open new possibilities in intensive chemotherapy for patients for whom haematopoietic progenitors are difficult to harvest. This may also represent an alternative to ex-vivo expansion and deserves further investigation.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Carmustine; Cytarabine; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Etoposide; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Cell Growth Factors; Humans; Lymphoma, Non-Hodgkin; Melphalan; Platelet Transfusion; Recombinant Proteins; Treatment Outcome

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

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

In the past 15 years, perspectives on treatment of patients with relapsed non-Hodgkin's lymphoma have changed. This has had important consequences for the costs of treatment. We conducted a retrospective study comparing the costs of four different treatment modalities in a university hospital in The Netherlands. The first group of patients received an autologous bone marrow transplantation (ABMT) and was kept in reverse barrier nursing. Their average total treatment costs amounted to US$26,539. Patients in the second group also received an ABMT but stayed on the normal hematology ward. The total average treatment costs for this group were US$20,806. In the third group, patients were transplanted with whole blood. Their average total treatment costs amounted to US$17,000. Patients in the fourth group received transplantation of autologous PBPC and their average total treatment costs were US$14,205. The decline in costs over time was mainly due to shorter hospitalization, less blood transfusions, and less parenteral nutrition. These factors also likely led to an improvement in patients' quality of life. The results of this study show that the progression in stem cell transplantation (SCT) techniques has been accompanied by significant benefits for patients and a decrease in costs.

Topics: Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Blood Transfusion; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Doxorubicin; Hematopoietic Stem Cell Transplantation; Hospital Costs; Hospital Units; Hospitalization; Humans; Length of Stay; Lymphoma, Non-Hodgkin; Melphalan; Netherlands; Parenteral Nutrition; Patient Isolation; Podophyllotoxin; Prednisone; Retrospective Studies; Transplantation, Autologous; 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

Mantle cell lymphoma (MCL) is currently regarded as one of the most incurable lymphomas, although reliable prognostic indicators are not yet to be defined. In a previous report, it was indicated that most of the patients with immunohistochemically cyclin D1(+)-MCL pursued the lethal clinical course within 7 years, not having achieved complete remission (CR). Recently, a high dose chemoradiotherapy was carried out, this was supported by peripheral blood stem cell transplantation (PBSCT) using the CD34(+)-selection method in a 48-year-old female patient with cyclin D1(+)-MCL. The tumor cells were detected in her peripheral blood despite four courses of combination chemotherapy using CHOP regimen. Soon after the pre-conditioning of total body irradiation (TBI) and high dose melphalan, she received the PBSCT of 1.8 x 10(6)/kg CD34+ cells and showed rapid hematological recovery without life-threatening complications. The patient achieved CR and was alive, without disease, 730 days after PBSCT. Thus, CD34+ selected PBSCT appears to provide further insight into the effective treatment and possible cure of this aggressive disease, i.e. cyclin D1(+)-MCL.

Topics: Antigens, CD34; Combined Modality Therapy; Cyclin D1; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged

The aim of the present trial was to investigate the feasibility of high-dose therapy followed by autologous peripheral blood stem cell transplantation (PBSCT) as a component of front-line treatment in patients with disseminated intermediate- and high-grade non-Hodgkin's lymphoma (NHL) aged 61-65 years. From October 1993 to June 1996, 14 consecutive patients entered this single-center prospective pilot trial. Patients were five males and nine females, median age 63 (range 61-65). The first-line treatment consisted of three courses of CHOP therapy. Patients achieving either a partial response (PR) or a complete response (CR) after initial therapy were eligible for PBSCT, while those with refractory or progressive disease were not autografted but included in the feasibility study in an intent-to-treat analysis. Of the 14 patients, 11 achieved either a CR (one) or a PR (10) after three courses of CHOP while the three patients with no response were not autografted and subsequently died of progressive disease. PBSC collection was feasible in responding patients after G-CSF priming (10 microg/kg/day for 6 days). Conditioning therapy was the BEAM protocol. All patients engrafted after PBSCT. The median time to granulocyte (>0.5 x 10(9)/l) and platelet recovery (>25 x 10(9)/l) was 12 (range 9-18) and 13 days (range 7-22), respectively. No toxic deaths VOD or IP were observed. Four of the 11 responding patients relapsed 2, 7, 9 and 12 months after PBSCT, respectively, and all died from progressive disease. Overall, 7/14 patients are alive and free from disease, 16-43 months after initial diagnosis (median 28). The actuarial overall survival is 45.7 %, and the actuarial event-free survival is 50% at 3.5 years. This study shows the feasibility of high-dose therapy and PBSCT in patients with intermediate- or high-grade disseminated NHL aged 61-65 years. Such patients should not be excluded from trials evaluating the role of ASCT as part of initial treatment for disseminated and histologically aggressive NHL.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Pilot Projects; Prednisone; Survival Rate; Transplantation, Autologous; Vincristine

To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution.. A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement.. Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS.. This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Disease-Free Survival; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Prognosis; Recurrence; Remission Induction; Retrospective Studies

We report on long-term haematological recovery and clinical outcome after high-dose chemotherapy supported by circulating progenitor cells (CPC) transplantation in non-Hodgkin's lymphoma (NHL) patients, and analyse the role of variables which might influence engraftment. 63 consecutive NHL patients were enrolled in this study. Two groups of patients were considered for analysis: the first 34 patients had untreated diffuse large cell lymphoma with unfavourable prognostic factors. A second group of 29 patients underwent transplantation for resistant or relapsing NHL with low, intermediate and high grade histology. All patients received the BEAM conditioning regimen. As already reported in many studies, all patients showed a rapid haematological reconstitution. 43 patients (68%) achieved long-term complete trilineage engraftment within a median of 107 d from CPC transplantation. The neutrophil count was the first parameter reaching complete normalization, and haemoglobin was the last. Failure to meet the trilineage levels was due to lack of platelet recovery and was more frequent in patients transplanted in the setting of salvage protocols. By Kaplan-Meier analysis, the probability of a full reconstitution was 80% in patients to whom transplant was offered as part of a front-line therapy and 50% when transplant was given in the salvage programmes. Multivariate analysis showed that sustained long-term haematological reconstitution was significantly related to younger age, the time taken to achieve short-term reconstitution, and bone marrow involvement.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Graft Survival; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hemoglobins; Humans; Leukocyte Count; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neutrophils; Platelet Count; Transplantation Conditioning

Mini-BEAM and ESHAP are two non-cross-resistant salvage regimens that have been used separately in patients with lymphoma. The aim of the present study was to investigate the efficacy of the combination of these two regimens, administered in alternating cycles, as salvage therapy for refractory non-Hodgkin's lymphoma (NHL) patients. A total of 28 patients were included in the study: 14 patients were primary refractory, seven were partial responders, and seven were in relapse. The alternating cycles of mini-BEAM and ESHAP were given until there was maximum response or progression. The overall response rate to mini-BEAM/ESHAP was 39%; 25% of patients achieved a complete response and 14% a partial response. Nevertheless, it should be noted that none of the primary refractory patients responded to this protocol. Nine of the 11 patients who responded to mini-BEAM/ESHAP were consolidated with autologous transplantation using BEAM as a conditioning regimen. The survival at 3 years in this group of 11 patients who responded to the salvage regimen is 64%, with a disease-free survival of 67% at 2 years. No major toxic effects were observed with mini-BEAM/ESHAP. Myelosuppression was the most frequent complication, especially with the mini-BEAM cycles. Other toxicities were infrequent and no treatment-related deaths were observed. These results suggest that alternating mini-BEAM/ESHAP chemotherapy is a safe regimen that is effective in partial responders or relapsing patients with NHL who have sensitive disease, but not in primary refractory patients. Moreover, although this therapy has a potential advantage, combining as it does two non-cross-resistant regimens, it does not seem superior to ESHAP alone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Cytarabine; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Methylprednisolone; Middle Aged; Myeloproliferative Disorders; Neutropenia; Salvage Therapy; Survival Rate; Time Factors

The role of intensive chemotherapy with autologous blood and marrow transplantation (ABMT) for patients with relapsed or refractory intermediate grade non-Hodgkin's lymphoma has recently been established. However, conventional dose salvage chemotherapy is frequently used to determine chemotherapy sensitivity and reduce tumor bulk prior to intensive therapy. Different salvage regimens have been proposed but none appears significantly superior. The purpose of this study was to determine the efficacy of mini-BEAM salvage chemotherapy in patients referred for AMBT and to define prognostic factors of response.. One hundred four patients referred for consideration of AMBT after failure of primary anthracycline-based chemotherapy received BCNU 60 mg/m2 day 1, etoposide 75 mg/m2 day 2-5, ara-C 100 mg/m2 q12 h day 2-5, melphalan 30 mg/m2 day 6 (mini-BEAM) until maximum tumor reduction. Median age was 52 (range 18-65), 57% had failed to achieve a complete response (CR) to doxorubicin-based chemotherapy at diagnosis and only 13% had a previous CR lasting > 12 months. Seventy-six received mini-BEAM as first salvage chemotherapy.. The overall response rate (RR) was 37% (95% confidence interval (CI) 28-46%) with 12 patients achieving CR and 25 achieving PR. The response rate among patients treated as first salvage was 43% compared to 20% for patients who had failed to respond to a previous salvage regimen. Only 15% of patients who failed to respond to mini-BEAM responded to another conventional dose salvage regimen. Thirty-eight of 104 patients ultimately demonstrated sufficient response to proceed to ABMT. Actuarial survival at four years is 22% for all 104 patients, and 36% for those who went on to AMBT. For those who were not transplanted, four-year survival was 18%. B symptoms and tumor burden at relapse were significant predictors of response to mini-BEAM in multivariate analysis, and identified a poor prognosis group of patients unlikely to be cured by the approach.. Mini-BEAM does not appear to be a superior salvage regimen in this high-risk group of relapsed or refractory NHL patients for whom ABMT was the ultimate treatment intention. Only one-third of patients referred for ABMT ultimately proceed to transplant; alternative treatment strategies should be developed for those with a low likelihood of cure by this approach.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cytarabine; Etoposide; Humans; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; Recurrence; Salvage Therapy; 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

Patients with intermediate grade non-Hodgkin's lymphoma (NHL) who relapse or fail to achieve a complete remission after anthracycline-containing induction regimens have a poor outcome with conventional-dose salvage treatment. This outcome may be improved with intensive therapy and autologous transplantation (ABMT) but even in patients with proven chemotherapy-sensitive disease, relapse rates of up to 60% are observed. Reliable and powerful prognostic indicators are needed to identify appropriate patients for this expensive procedure and those subjects to whom alternative or additional treatment should be offered. We were interested in testing the hypothesis that tumour burden, and hence remission status immediately prior to transplant, is an important prognostic indicator of survival. We aggressively treated patients with conventional-dose salvage chemotherapy to maximum tumour response, and tested, by multivariate regression analysis, predictors of outcome post-transplant. We studied 81 consecutive patients with intermediate grade and immunoblastic NHL who achieved either a partial (PR) or complete remission (CR) following repetitive cycles of conventional-dose salvage therapy. Intensive therapy consisted of etoposide (60 mg/kg) and intravenous melphalan (160-180 mg/m2) with or without total body irradiation (TBI) followed by infusion of autologous unpurged bone marrow and/or blood cells. The predicted 4-year survival and progression-free survival (PFS) with a median follow-up of 37 months was 58% and 48% (95% confidence interval (CI) 37-55%), respectively. The only factor predictive of outcome was remission status at transplant (P=0.0001). The PFS at 4 years for the CR group was 61% (95% CI 53-75%). In contrast, only 25% (95% CI 11-40%) of patients undergoing autotransplant in PR were progression free at 4 years. We conclude that remission status at transplant after maximum tumour reduction is a powerful prognostic indicator.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Bone Marrow Transplantation; Disease-Free Survival; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Prognosis; Recurrence; Salvage Therapy; Survival Analysis; Transplantation, Homologous

Bifunctional alkylating agents, such as melphalan, are widely used in the treatment of hematological malignancies. The effects of these drugs on particular types of hematological cells and the causes of treatment failure are poorly understood. The aim of this work was to establish an ability to measure the extent to which melphalan reacts with the DNA of individual tumor cells, thereby creating new possibilities for molecular pharmacological studies on clinical samples. A novel approach for staining drug-DNA adducts is described in which cells were embedded in agarose and then lysed. The DNA from each cell remained in an ideal state for quantitative immunofluorescent staining using a previously described monoclonal antibody. Immunofluorescence and DNA-Hoechst dye fluorescence were quantified using a cooled slow scan charge coupled device camera and image analysis procedures. Immunofluorescence of drug-treated cells from a human leukemia cell line was partially correlated with DNA content. Mean integrated immunofluorescence of 50 to 100 cells was dependent on drug concentration and was linearly related to adduct levels. In these cells and in chronic lymphocytic leukemia cells obtained from patients, there was considerable intercell heterogeneity in apparent adduct levels. This was also seen in peripheral blood mononuclear cells isolated from a patient after melphalan therapy.

Topics: Antineoplastic Agents, Alkylating; Bisbenzimidazole; DNA Adducts; DNA, Neoplasm; Feasibility Studies; Fluorescent Dyes; Hematopoietic Stem Cells; Humans; Image Processing, Computer-Assisted; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Melphalan; Neoplastic Stem Cells; Sepharose; Staining and Labeling; Tissue Embedding; Tumor Cells, Cultured

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

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

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

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

Adriamycin containing combination chemotherapy (ACCC) is usually delivered to patients with stages III, IV diffuse large cell (DLCL) non-Hodgkin's lymphoma (NHL). Although this mode of therapy is also commonly used in other intermediate grade lymphomas, it's role in the latter subset of patients is not well defined. In a retrospective analysis we evaluated and compared the outcome of previously untreated DLCL and non-DLCL intermediate grade lymphoma patients who received as initial therapy, "first generation" ACCC. No differences in response and relapse rates between these subgroups were observed. The trend towards the survival advantage observed for the non-DLCL patients, is probably due to a lower mortality over 5-8 years, for complete responders.

Topics: Actuarial Analysis; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cyclophosphamide; Dexamethasone; Doxorubicin; Etoposide; Follow-Up Studies; Humans; Leucovorin; Lomustine; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Methotrexate; Middle Aged; Phosphoramide Mustards; Prednisolone; Prednisone; Prognosis; Retrospective Studies; Survival Analysis; Time Factors; Treatment Outcome; Vincristine

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

Seven children with advanced neuroblastoma and non-Hodgkin's lymphoma were treated with myeloablative chemoradiotherapy (180 mg/m2 melphalan plus 12 Gy fractionated total body irradiation), followed by autotransplantation of peripheral blood stem cells (PBSC). Sufficient PBSC to restore bone marrow function were collected by a small number of leukaphereses during haematopoietic recovery after chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF). Furthermore, rapid recovery of neutrophils was found in all patients by the administration of rhG-CSF following transplantation: median 10 d (range 8-12) to attain more than 0.5 x 10(9)/l neutrophils, and 27 d (range 14-73) to attain more than 50 x 10(9)/l platelets, respectively. Haematopoietic reconstitution has been maintained throughout the follow-up period (median 15 months; range, 6-22). Peripheral blood stem cells mobilized by chemotherapy and rhG-CSF can induce complete haematopoietic reconstitution after myeloablative chemoradiotherapy.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion, Autologous; Child; Child, Preschool; Combined Modality Therapy; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Leukocyte Count; Lymphoma, Non-Hodgkin; Male; Melphalan; Neuroblastoma; Neutrophils; Recombinant Proteins; Whole-Body Irradiation

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

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

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

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Child; Cytarabine; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Retrospective Studies

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Colony-Stimulating Factors; Cytarabine; Granulocyte Colony-Stimulating Factor; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Recombinant Proteins

A 61-year-old man with an intractible and progressively disabling cutaneous non-Hodgkin's lymphoma (NHL) in the lower limb was treated with sequential regional isolated perfusion at 10-day intervals. The first perfusion was hyperthermic (40.2-43.1 degrees C tumor-temperature); the second was at controlled normothermia with high-dose 1-phenylalanine mustard (melphalan, L-Pam; 11 mg/l perfused tissue). This treatment resulted in a complete remission in the perfused area of significant duration and has prevented amputation.

Topics: Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Humans; Hyperthermia, Induced; Leg; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Skin Neoplasms

The paper is concerned with the results of a morphological study following chemoradiotherapy in 25 patients with Ewing's sarcoma and 14 patients with reticulum cell sarcoma. The signs of therapeutic pathomorphosis were observed in the first 3 days, and substitution of the connective tissue for a necrotized tumor started by the 3rd-4th week after the initiation of therapy. In some cases tumor growth and recurrences at the site of a treated tumor were observed.

Topics: Combined Modality Therapy; Humans; Lymphoma, Non-Hodgkin; Melphalan; Sarcoma, Ewing

Three cases of secondary leukemia developing after chemotherapy and/or radiotherapy for myeloma, mycosis fungoides, and non-Hodgkin's lymphoma are reported. The first case was a 51-year-old man with IgG-lambda myeloma, treated with melphalan and prednisolone, who developed acute myelomonocytic leukemia 54 months after the diagnosis of myeloma. The second case was a 54-year-old woman with mycosis fungoides treated with radiation, predonine, and cyclophosphamide, who developed acute megakaryoblastic leukemia 298 months after the diagnosis of mycosis fungoides. The third case was a 35-year-old woman with stage IV non-Hodgkin's lymphoma treated with VEMP who developed acute myelogenous leukemia 26 months after the diagnosis of malignant lymphoma. All cases showed pancytopenia and two of three cases had morphologic abnormality in several hemopoietic cell lineages in the leukemic stage. There is a possibility that second malignancies are an increasingly recognized complication in the patients treated with a large amount of chemo-radiotherapy.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Lymphoma, Non-Hodgkin; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma; Mycosis Fungoides; Pancytopenia; Prednisolone; Vincristine

Antitumor and antimetastatic effects of an official extract of Rhodiola rosea were established in experiments on inbred and noninbred mice and rats with transplantable NK/Ly tumor, Ehrlich's adenocarcinoma, melanoma B16 and Lewis lung carcinoma. Application of the said preparation to sarcolysin-treated animals was followed by an increase in survival.

Topics: Animals; Carcinoma, Ehrlich Tumor; Drug Evaluation, Preclinical; Lymphoma, Non-Hodgkin; Male; Melanoma, Experimental; Melphalan; Mice; Mice, Inbred Strains; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Transplantation; Neoplasms, Experimental; Plant Extracts; Rats; Rats, Inbred Strains; Sarcoma 180; Time Factors

Administration to hamsters of a highly purified human leukocyte interferon subtype, IFN-alpha A, obtained by recombinant DNA methods, abolished the efficacy of high doses of cyclophosphamide (2.5 mg/hamster) against the TBD 932 lymphosarcoma. The effect was more pronounced with concomitant than with sequential treatments and did not occur with melphalan. Antagonistic effects occurred at high interferon doses (10(5) I.U./treatment), but an additive or synergistic positive effect occurred at lower interferon doses (10(3) I.U./treatment) and at lower, non-protective, doses of cyclophosphamide. These effects may be due to immunomodulatory responses induced by the drugs involved.

Topics: Animals; Cricetinae; Cyclophosphamide; Cytochrome P-450 Enzyme System; Drug Interactions; Female; Immunity; Interferon Type I; Lymphoma, Non-Hodgkin; Melphalan; Mesocricetus

A 47-year-old woman developed a unique myeloproliferative disorder 36 months after receiving adjuvant chemotherapy postoperatively for breast carcinoma. Her bone marrow and peripheral blood exhibited many of the myelodysplastic changes commonly observed in treatment-linked leukemia. In addition, there was striking marrow and blood eosinophilia and eosinophilic infiltration in multiple organs. She also developed a poorly differentiated lymphocytic lymphoma which responded to therapy. Her myeloproliferative disorder, with marked eosinophilia, continued to progress, however, and she died shortly after its diagnosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Eosinophilia; Female; Humans; Lymphoma, Non-Hodgkin; Mastectomy; Melphalan; Middle Aged; Myeloproliferative Disorders; Prednisone; Vincristine

Topics: Adolescent; Bone Neoplasms; Child; Female; Humans; Lung; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Melphalan; Sarcoma, Ewing; Time Factors; Whole-Body Irradiation

Topics: Animals; Daunorubicin; Drug Evaluation, Preclinical; Drug Resistance; Drug Therapy, Combination; Flavonoids; Fluorouracil; Hematopoiesis; Lymphoma, Non-Hodgkin; Male; Melphalan; Neoplasm Transplantation; Neoplasms, Experimental; Rats

Topics: Adult; Drug Therapy, Combination; Female; Humans; Hyperthermia, Induced; Lymphoma, Non-Hodgkin; Male; Melphalan; Myeloproliferative Disorders; Plasmacytoma; Pyrogens; Radiotherapy Dosage; Sarcoma, Ewing

Topics: Animals; Bence Jones Protein; Blood Viscosity; Cat Diseases; Cats; Dog Diseases; Dogs; Hemorrhagic Disorders; Hypercalcemia; Hypergammaglobulinemia; Kidney Diseases; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Waldenstrom Macroglobulinemia

DNA/cell distributions were recorded by automated cytofluorometry (=pulse cytophotometry) in bone-marrow aspirates of leukaemia and lymphosarcoma patients subjected to chemotherapy. In most cases, early perturbations in DNA/cell histographs were observed, characteristically reflecting the known mode of action of the drugs. These changes in general preceded the clinical observation of drug response. In a series of 23 measurements in 19 patients, a positive correlation between early cytophotometric changes and clinical effects of chemotherapy was observed in 17 patients. Five patients were negative for both cytophotometric and clinical reactions and one patient was probably false-positive. The validity of the assay for early detection of drug resistance in acute leukaemia and related diseases is discussed.

Topics: Adult; Antineoplastic Agents; Asparaginase; Bone Marrow; Bone Marrow Cells; Cell Division; Child; Cytarabine; DNA, Neoplasm; Doxorubicin; Fluorometry; Humans; Leukemia; Lymphoma, Non-Hodgkin; Melphalan; Prednisone; Vincristine

Topics: Administration, Oral; Adolescent; Aged; Chemotherapy, Cancer, Regional Perfusion; Cyclophosphamide; Female; Fibrosarcoma; Humans; Knee; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Retroperitoneal Neoplasms; Sarcoma; Stomach Neoplasms

Topics: Adolescent; Adult; Aged; Child; Fibrosarcoma; Giant Cell Tumors; Hemangiosarcoma; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Maxillary Neoplasms; Melphalan; Middle Aged; Myxosarcoma; Osteosarcoma; Radioisotope Teletherapy; Sarcoma; Thiotepa

Topics: Animals; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Female; Leukopenia; Lung Neoplasms; Lymphoma, Non-Hodgkin; Melphalan; Mice; Neoplasm Metastasis; Ovarian Neoplasms; Peritoneal Neoplasms; Rats; Sarcoma 180; Sarcoma, Experimental; Thiotepa; Triazines

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Female; Fluorouracil; In Vitro Techniques; Lymphoma, Non-Hodgkin; Melphalan; Mice; Neoplasms, Experimental; Ovarian Neoplasms; Rats; Thiotepa

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Busulfan; Drug Synergism; Lymphoma, Non-Hodgkin; Melphalan; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Oligomycins; Thiotepa; Uracil Mustard

Topics: Abdominal Neoplasms; Angiography; Breast Neoplasms; Geriatrics; Gold; Humans; Injections; Iodine Isotopes; Leukemia; Lymphatic Metastasis; Lymphatic System; Lymphography; Lymphoma; Lymphoma, Non-Hodgkin; Melanoma; Melphalan; Methotrexate; Neoplasms; Radioisotopes; Radionuclide Imaging; Retroperitoneal Neoplasms; Scandium; Thiotepa; Yttrium

Topics: Female; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Melphalan; Multiple Myeloma; Neoplasms; Osteosarcoma; Ovarian Neoplasms; Research; Sarcoma; Sarcoma, Ewing; Testicular Neoplasms; Thymoma

Topics: Animals; Carcinoma 256, Walker; DNA; DNA, Neoplasm; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Phosphorus Isotopes; Rats; Research; RNA; RNA, Neoplasm; Sarcoma; Sarcoma, Yoshida; Tissue Culture Techniques

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: Aorta; Aorta, Abdominal; Bone Neoplasms; Carotid Arteries; Chemotherapy, Cancer, Regional Perfusion; Chondrosarcoma; Dactinomycin; Dogs; Fibrosarcoma; Iliac Artery; Iliac Vein; Leiomyosarcoma; Liposarcoma; Lymphoma, Non-Hodgkin; Melphalan; Mesothelioma; Neoplasms; Neuroblastoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Kaposi; Subclavian Artery; Vena Cava, Inferior

Topics: Adenine; Bone Marrow Transplantation; Breast Neoplasms; DNA; Female; Folic Acid; Humans; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Neoplasms; Ovarian Neoplasms; Perfusion; Sarcoma; Thiotepa; Triethylenemelamine

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: 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: Aminopterin; Antineoplastic Agents; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Chlorambucil; Dactinomycin; Fibrosarcoma; Fluoresceins; Humans; Infusions, Parenteral; Injections, Intra-Arterial; Lymphoma; Lymphoma, Non-Hodgkin; Melanoma; Melphalan; Neoplasms; Pharmacology; Thiotepa; Toxicology

Topics: Lymphoma, Non-Hodgkin; Mechlorethamine; Melphalan; Nitrogen Mustard Compounds

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