Combination chemotherapy for advanced non-Hodgkin's lymphomas other than diffuse histiocytic or undifferentiated histologies.

A combination chemotherapy program using methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M-BACOD), which resulted in a high complete response rate and prolonged disease-free survival in lymphomas of the unfavorable diffuse histiocytic and diffuse undifferentiated histopathologic subgroups, was administered to 44 patients with advanced favorable and intermediate-prognosis non-Hodgkin's lymphomas, including nodular lymphoma of the poorly differentiated lymphocytic, mixed, and histiocytic subtypes, and diffuse lymphoma of the poorly differentiated lymphocytic or mixed histologic subtypes. High-dose methotrexate (3 g/m2) was given on Day 14 between cycles of bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone, administered every 3 weeks for ten cycles. Leucovorin factor (10 mg/m2) was given iv 24 hours after the methotrexate infusion was completed, and was continued at 10 mg/m2 by mouth every 6 hours for 72 hours. Therapy was well-tolerated, with predictable myelosuppression in the majority of patients. The complete response rate was 57% (25 of 44 patients), including ten of 18 (56%) patients with nodular and 15 of 26 (58%) patients with diffuse lymphomas. Median overall follow-up among living patients is 65 months, 58 months for patients with nodular and 69 months for patients with diffuse histologic subgroups. Overall survival at 5 years was 64% for patients who achieved complete response, 32% for partial responders, and 0% for those patients who did not respond. Disease-free survival of complete responders was 43% at 5 years, with only one disease-related death noted after 36 months. The nodular and diffuse patient subgroups had similar overall and disease-free survivals. Although initial bone marrow involvement was documented in nine of 18 (50%) nodular patients and in 13 of 26 (50%) diffuse patients, CNS relapse occurred in only one complete and two partial responders. The prolonged disease-free survival observed after M-BACOD therapy demonstrates that durable responses can be achieved with intensive chemotherapy.