To achieve long-term disease-free survival, high-dose therapy and autologous stem cell transplantation (ASCT) is the current standard approach in patients with relapsed or refractory Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL). Because chemosensitivity is a significant factor in determining transplantation eligibility, it is critical to select a salvage chemotherapy regimen that has the potential to induce a high response rate with low nonhematologic toxicity. In this phase II study, 49 patients with relapsed or refractory HD (n = 22) and NHL (n = 27) with a median age of 42 years were treated with an IIVP salvage regimen consisting of ifosfamide, idarubicin, and etoposide. Twenty-seven percent of the patients had primary refractory disease, whereas 22% and 51% had early and late relapses, respectively. As analyzed by intention to treat, 16 patients (33%) achieved complete remission and 21 patients (43%) achieved a partial response, leading to an overall response rate of 76% (63% in NHL and 91% in HD). In the univariate analysis, diagnosis (HD versus NHL), remission duration before the initiation of IIVP, disease bulk, increased lactate dehydrogenase, and the presence of "B" symptoms were significant factors affecting the response achieved by the IIVP regimen. Of 37 responders, 31 (84%) underwent high-dose therapy and transplantation. The probability of 4-year overall survival (OS) and event-free survival (EFS) in this group of patients who underwent ASCT was 67.7% and 49.1%, respectively. When compared with the patients who achieved a partial response, patients who achieved complete remission with the IIVP regimen had a significantly higher probability of 4-year EFS (67.3% versus 30%; P =.016) and 4-year OS (92.3% versus 39.2%; P =.003). In patients with HD, 4-year EFS and 4-year OS were 54.9% and 70.6%, respectively, without a significant difference with respect to the survival rates obtained in patients with NHL (43.6% and 63.6%, respectively). Common side effects observed during 102 cycles of therapy were grade 3 to 4 neutropenia (62%) and thrombocytopenia (58%). The IIVP regimen is a highly effective salvage regimen for patients with relapsed or refractory HD or NHL who are candidates for ASCT. Furthermore, the degree of response to IIVP predicts the posttransplantation outcome. However, close follow-up is necessary because of a high incidence of grade 3 to 4 hematologic toxicity. (c) 2005 American Society for Blood and Marrow Transplantation.