High-Dose Cytosine Arabinoside and Mitoxantrone (HAM) for the Treatment of Refractory Acute Lymphoblastic Leukemia

Abstract

In a clinical phase-II study 11 patients with refractory ALL were treated with high-dose AraC and mitoxantrone in combination (HAM). Refractoriness was defined as: 1. primary resistance against the BMFT induction protocol; 2. first relapse with non-response to the B-ALL/NHL regimen as salvage treatment; 3. second and subsequent relapses. Therapy consisted of HD-AraC 3 g/m2 every 12 h by a 3-h infusion on days 1-4 and mitoxantrone 10 mg/m2/d on days 2-6. Seven of the 11 patients achieved a complete remission, 1 patient was refractory against 2 HAM cycles and 3 patients died during bone marrow aplasia. Toxicity was acceptable, consisting mainly of nausea and vomiting, mucositis and diarrhea. One patient who had completed the prophylactic CNS treatment with intrathecal MTX and cranial irradiation immediately before entering the HAM protocol developed severe signs of cerebral toxicity. These data indicate a significant activity of HAM in refractory ALL and suggest that the combination should be applied at earlier stages of ALL treatment.