We performed a phase II study to determine the efficacy of maximal cytoreductive therapy with up to five cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) for patients with advanced relapsed or refractory indolent lymphoma. Thirty-two patients with primary refractory or relapsed indolent lymphoma were treated with the Dexa-BEAM regimen. Thirteen patients had primary refractory disease, 4 patients partial remission, and 15 patients first or subsequent relapse. Patients achieving PR or CR received HDCT with ASCT. The conditioning regimen used was BEAM (carmustine [BCNU], etoposide, cytarabine, and melphalan). Twenty-two patients responded to Dexa-BEAM resulting in a response rate of 78%. Maximum response was observed after 3.2 (range 2-5) courses. One patient with progressive disease died in septic shock during neutropenia. Nineteen patients with partial or complete remission after Dexa-BEAM received HDCT. Hematopoietic stem cells (HSC) were collected after two cycles of Dexa-BEAM. The median number of CD34+ HSC reinfused was 3.1 x 10(6)/kg (range 1.6-8.2 x 10(6)/kg). There was no transplantation-related death. All patients receiving HDCT achieved complete remission. Overall survival (OS) and freedom from treatment failure (FFTF) for all patients are estimated to be 68% and 65% at two years, respectively. With a mean follow-up of 20 months (range 8-42 months), 16/19 patients receiving HDCT are in continuous complete remission. The Dexa-BEAM regimen is effective in overcoming drug resistance in patients with indolent lymphoma who failed to respond to conventional treatment or who relapsed. The CR rate of 100% of those patients receiving HDCT and ASCT after maximal cytoreductive treatment with Dexa-BEAM suggests the use of HDCT at the time of maximal response.