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A salvage program including infusional high-dose ifosfamide plus etoposide (IFOVM) was evaluated in patients with refractory or relapsed aggressive non-Hodgkin's lymphoma. DESIGN AND METHODS: Forty-six patients were included. IFOVM consisted of ifosfamide (10 g/m2 as a 72-hour continuous infusion), etoposide (900 mg/m2) and methylprednisolone; responding patients underwent two cycles of DHAP and subsequently an autologous peripheral blood stem cell transplantation (APBSCT) with BEAM as the conditioning regimen. RESULTS: All but one patient showed tumor regression following IFOVM. Myelosuppression was brief but 26 patients developed neutropenic fever. All but two patients proceeded to DHAP. Overall response rate to IFOVM/DHAP was 59% (29% CR and 30% PR). Refractory patients had a significantly lower response rate than relapsed patients (39% vs. 85% p=0.002). All refractory patients with intermediate-high or high IPI progressed during IFOVM/DHAP. Twenty-seven patients proceeded to APBSCT. Two-year overall survival of patients with low or low-intermediate IPI was 47% [95% CI 25-69%], which was significantly better than that obtained in patients with intermediate-high or high IPI (11% [95% CI 0-22%] p=0.0001). INTERPRETATION AND CONCLUSIONS: This sequential regimen of IFOVM, followed by DHAP and consolidated with BEAM is active in relapsed or refractory patients with low or low-intermediate IPI aggressive lymphoma. However, it has little activity in those patients with intermediate or high IPI, especially in refractory lymphomas.