Phase-II study of treatment of refractory acute leukemia with intermediate-dose cytosine arabinoside and amsacrine.

Twenty-five consecutive leukemia patients (21 AML, 4 ALL) with either primary resistance (n = 22) or resistant relapse (n = 3) of all FAB subtypes were treated with 1 or 2 cycles of ID-ara C (1 g/m2 i.v. q 12 h, days 1-6) and AMSA (120 mg/m2 i.v., days 5-7). Patients reaching CR received 1 cycle of intensive consolidation using ara C 3 g/m2 i.v. q 12 h, days 1-4 and AMSA 120 mg/m2 i.v., day 5. Two patients received an allograft thereafter and are still alive and in CCR. CR was achieved in 12/25 patients (48%), ten after 1 cycle of induction and two after 2 cycles; 10/22 patients with primary resistant disease reached CR, and 2/3 with resistant relapse. Nine patients remained refractory (36%) and four died during hypoplasia (16%). Median DFS of the 12 responders was 2.9 months, median survival from time of CR 8.9 months. Median overall survival of responders and nonresponders was 6 months from time of resistance. Survival advantage of responding patients (n = 12) as compared with nonresponders (n = 13) was 10.7 vs. 3.2 months (p = 0.002). Toxicity of chemotherapy was acceptable: one patient experienced pulmonary edema due to ara C; two patients developed life-threatening systemic fungal infections, one of whom died while in CR.