Chemotherapy Before Autologous Stem Cell Transplantation +/- Rituximab in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

OBJECTIVES: Salvage therapy Primary * Compare the response rate and transplantation rate in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma when treated with salvage chemotherapy comprising dexamethasone, cisplatin, and gemcitabine with or without rituximab vs a standard platinum-based regimen (dexamethasone, cisplatin, and high-dose cytarabine with or without rituximab). * To compare the transplantation rates of the two protocol salvage regimens. Secondary * Compare the event-free and overall survival of patients treated with these regimens. * Compare the success rate of these regimens, in terms of getting patients to autologous stem cell transplantation and successful mobilization after high-dose chemotherapy. * Compare the quality of life of patients treated with these salvage regimens. * Compare the toxic effects of these salvage regimens in these patients. * Compare resource utilization for patients treated with these salvage regimens. * Compare relative medical and societal costs of these salvage regimens with outcomes in these patients. Maintenance therapy Primary * Compare the 2-year event-free survival of patients with CD20+ B-cell lymphoma treated with maintenance rituximab after these salvage regimens and autologous stem cell transplantation to those patients who received no further treatment. Secondary * Compare the 2-year survival of patients treated with or without maintenance rituximab. * Compare the toxic effects of rituximab vs observation alone in these patients. OUTLINE: This is a randomized, multicenter study. For salvage therapy, patients are stratified according to participating center, International Prognostic Index score at relapse/study entry (0 or 1 vs 2 vs ≥ 3), immunophenotype (B cell vs T cell), response to or response duration after initial chemotherapy (no response or progressive disease vs \> 1 year vs ≤ 1 year), and prior rituximab (yes vs no). For maintenance therapy, patients are stratified according to participating center, salvage therapy treatment randomization (with or without rituximab, cisplatin, dexamethasone, and gemcitabine vs with or without rituximab, cisplatin, dexamethasone, and cytarabine), response to salvage therapy (complete response \[CR\] and CR unconfirmed \[CRu\] vs partial response \[PR\] vs stable disease \[SD\]), and prior rituximab (yes vs no). * Salvage therapy: Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1. * Arm II: Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1. In both arms, treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients are reassessed after 2 courses. Patients with progressive disease are removed from study. Patients with a CR, CRu, or PR proceed to autologous stem cell transplantation (ASCT). Patients with SD may proceed to ASCT or receive 1 additional course of salvage therapy at the discretion of the investigator. Patients receiving an additional course of salvage therapy are then reassessed after the completion of therapy. Patients with progressive disease are removed from study. Patients with a PR proceed to ASCT. Patients with SD may proceed to ASCT or be followed off study at the discretion of the investigator. * ASCT: Responding patients (or those with stable disease, if that is the center's policy)undergo mobilization, stem cell harvest, and subsequent ASCT. Patients with CD20+ B-cell disease are randomized to maintenance therapy or observation. * Maintenance therapy: Patients are randomized to 1 of 2 treatment arms. * Arm I: Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity. * Arm II: Patients undergo observation only. Quality of life is assessed at baseline, days 1 and 10 of course 2, day 1 of course 3 (if given), on the last day of salvage therapy (or the first day of mobilization, if given), and at 1 month posttransplantation. Patients who undergo ASCT are followed at months 1, 3, 7, 13, 19, and 25 and then annually thereafter. Patients who complete salvage therapy, but do not undergo ASCT are followed at months 4, 8, 14, 20, and 26 and then annually thereafter. Patients who relapse or progress are followed every 6 months until 25 months from ASCT or 26 months from completion of salvage therapy and then annually thereafter. PROJECTED ACCRUAL: A total of 637 patients will be accrued for this study within 3-4 years for the first randomization, and 240 transplanted CD20+ patients will be needed for the second randomization.