Ifosfamide, etoposide, cytarabine, and methotrexate as salvage chemotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma

BACKGROUND: Patients with relapsed or resistant non-Hodgkin's lymphoma (NHL) have a poor prognosis and are rarely cured with usual salvage chemotherapy. Intensive treatment with the support of peripheral blood stem cells (PBSC) may be an effective therapy for these patients. We used a combination of ifosfamide, etoposide, cytarabine, and methotrexate (IVAM) with the intention both to reduce tumor burden and collect PBSC prior to transplantation. METHODS: Thirty-one patients (17 with relapsed NHL and 14 with refractory NHL) were treated with 2 courses of chemotherapy: IVAM regimen (ifosfamide, 1500 mg/m2 daily for 5 days plus mesna; etoposide, 150 mg/m2 daily for 3 days; cytarabine, 100 mg/m2 daily for 3 days; and methotrexate, 3 g/m2 on Day 5, with leucovorin rescue). Twenty-three patients had an intermediate grade and 8 patients had a high grade lymphoma. RESULTS: After IVAM therapy, 19 patients (61%) achieved complete response, 8 patients (26%) achieved partial response and 4 patients (13%) failed to respond. The major toxicity of IVAM was myelosuppression, but there were no toxic deaths. PBSC harvest could be performed in 29 patients (94%) with a median granulocyte-macrophage colony-forming unit count of 55 x 10(4)/kg (range, 2-391 x 10(4)/kg). Three patients could not undergo transplantation because of disease progression. One patient received a syngeneic transplant, 25 patients received PBSC transplantation, and 2 patients received a bone marrow transplant. In an intent-to-treat analysis, the overall survival rate at 4 years was 37% for the whole group (95% confidence interval: 22-55). CONCLUSIONS: We conclude that IVAM is an effective salvage chemotherapy for refractory or relapsed NHL and permits PBSC collection in most of these patients.