Phase II study of etoposide, ifosfamide, and mitoxantrone for the treatment of resistant adult acute lymphoblastic leukemia

Although combination chemotherapy induces complete remission in 60–90% of adults with acute lymphoblastic leukemia, only 20–45% of patients remain in continued remission 5 years from diagnosis. For patients with a short first remission, multiple relapses, or patients with disease refractory to initial induction chemotherapy, few salvage treatments are successful. To improve the results of salvage therapy we studied the efficacy and toxicity of a combination of etoposide (100 mg/m² IV qd × 5), ifosfamide (1.5 g/m²/d × 5), and mitoxantrone (8 mg/m²/d IV × 3) in 11 adult patients with relapsed or refractory ALL. The median follow‐up of all patients completing therapy is 208 days (30–484+ days). Eight of 11 (73%; 95% confidence interval 45–92%) achieved a complete remission, two patients failed to enter remission, and one patient died of multiorgan system failure shortly after receiving therapy. Median DFS is 96 days and median survival from remission is 234 days. Five patients who achieved CR subsequently relapsed with a median time to relapse of 80 days (50–151 days). Median time to granulocyte > .5 × 10⁹/L was 28 days (21–46 days) and the median time to platelet recovery > 20 × 10⁹/L was 24 days (21–39 days). Although gastrointestinal toxicity was common, no patient developed severe cardiac, hepatic, pulmonary, or neurologic complications. These results demonstrate that the combination of etoposide, ifosfamide, and mitoxantrone can be used as an effective salvage therapy for patients with resistant ALL.