The role of upfront autologous stem cell transplantation (ASCT) in low-grade non-Hodgkin's lymphoma (LGNHL) continues to be an area of investigation. After undergoing this novel anthracycline-based induction regimen including interferon (IFN)-alpha, a group of LGNHL patients received high-dose chemotherapy followed by ASCT. The induction regimen was based on the concept of regrowth resistance in which patients received nonmyelotoxic agents mid-cycle to slow tumor proliferation between courses of cytotoxic therapy. In addition, IFN-alpha was given at the end of the cycle because studies have shown that it has a 50% response rate in treating LGNHL. We treated 44 consecutive patients between August 1993 and February 1999 with an induction regimen containing cyclophosphamide, mitoxantrone, and teniposide intravenously on day 1 with oral prednisone given on days 1-5. On day 15, patients received vincristine and bleomycin IV. IFN-alpha-2b subcutaneously was administered on days 22-26. In this phase II single-institution study, there were 2 main patient groups. Nineteen patients received the chemotherapy induction regimen and 17 patients received chemotherapy followed by upfront ASCT. For the chemotherapy group, 58% had follicular histology and 84% had stage IV disease. For the ASCT group, 76% had follicular histology, and 71% had stage IV disease. Of the patients treated with chemotherapy, the overall response rate was 95% with 58% complete responses and 37% partial responses. Of the patients treated with chemotherapy and later ASCT, the overall response rate was 100% with 82% complete responses and 18% partial responses. In analyzing progression-free curves for these 2 groups of patients, there was evidence that the upfront autologous group fared better, log-rank test X(2)=4.6028, P < .0319.