OBJECTIVES:
* Compare the disease-free survival of patients with previously untreated advanced mantle cell lymphoma treated with intensified chemotherapy followed by myeloablative radiochemotherapy and peripheral blood stem cell transplantation (PBSCT) vs standard therapy and interferon alfa maintenance.
* Compare the overall survival of patients treated with early vs late myeloablative radiochemotherapy and PBSCT.
* Compare disease-free survival and overall survival of patients treated with this regimen vs historic controls of similar cases.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk factors (ECOG performance status greater than 1, LDH serum level above normal, and/or extranodal lymphoma involvement) and participating center. Patients are randomized to 1 of 2 treatment arms.
* Induction: All patients receive 4 courses of cytoreductive chemotherapy comprising an anthracycline-containing combination. Patients not achieving complete remission after 4 courses receive 2 additional courses of induction chemotherapy. Patients without at least a partial response after 6 courses discontinue treatment; those with at least a partial response proceed to arm I or II.
Arm I
* Consolidation: Patients achieving complete or partial remission after 4-6 courses of induction therapy begin intensified chemotherapy within 6 weeks. Patients receive oral dexamethasone daily on days 1-10, carmustine IV on day 2, melphalan IV on day 3, etoposide IV daily and cytarabine IV twice a day on days 4-7. Patients also receive filgrastim (G-CSF) beginning on day 11 and continuing until peripheral blood stem cells (PBSC) are harvested.
* Within 4-6 weeks after PBSC harvest, patients undergo myeloablative radiochemotherapy comprising radiotherapy on days -6 to -4 and cyclophosphamide IV on days -3 to -2. Patients then undergo PBSC transplantation on day 0.
Arm II
* Consolidation: Patients receive 2 additional courses of induction chemotherapy as consolidation (for a total of 8 chemotherapy courses).
* Maintenance: Within 4 weeks after arm II consolidation, patients receive interferon alfa subcutaneously (SC) 3 days a week in the absence of unacceptable toxicity or disease progression or relapse. Patients who experience first relapse or progression during maintenance therapy may receive intensified chemotherapy as in arm I.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 210 patients will be accrued for this study within 5 years.
