Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin's lymphoma: an Italian multicenter randomized trial.

PURPOSE: To evaluate the role of early intensification with high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) as front-line chemotherapy for patients with high-risk, histologically aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: We planned a multicenter, randomized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B; arm A) with an abbreviated regimen of MACOP-B (8 weeks) followed by HDT and ASCT (arm B) for intermediate-high-risk/high-risk patients (according to the age-adjusted International Prognostic Index). From September 1994 to April 1998, 150 patients with aggressive lymphoma were enrolled onto the trial. Seventy-five patients were randomly assigned to arm A and 75 patients were randomly assigned to arm B. In both arms, involved-field radiation therapy (36 Gy) was delivered to the site of bulky disease. RESULTS: The rate of complete response was 68% in arm A and 76% in arm B (P = not significant [NS]). Three toxic deaths (4%) occurred in arm B and one (1%) occurred in arm A (P = NS). In arm B, 30 patients (40%) did not undergo HDT and ASCT. According to the intention-to-treat analysis at a median follow-up of 24 months, 5-year overall survival probability in arms A and B was 65% and 64% (P =.95), 5-year progression-free survival was 49% and 61% (P =.21), and 5-year relapse-free survival was 65% and 77% (P =.22), respectively. CONCLUSION: Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk, aggressive NHL. Additional randomized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients.