Intermediate-dose Ara-C/m-AMSA for remission induction and high-dose Ara-C/m-AMSA for intensive consolidation in relapsed and refractory adult acute myelogenous leukemia (AML)

Abstract

Twenty nine consecutive patients (pts) with either relapsed (n = 23) or primary refractory AML (n = 6) were treated with 1 or 2 cycles of intermediate-dose (ID) ara-C (1g/m2 IV q 12 h days 1-6) and m-AMSA (120 mg/m2 IV days 5-7). Pts reaching complete remission (CR) were consolidated with 1 cycle of ara-C 3 g/m2 IV q 12 h days 1-4 and m-AMSA 120 mg/m2 IV day 5. The median duration of the preceding remission was 9.5 months, median time from last chemotherapy until relapse 3 months. 18/23 (78%) of relapsed pts achieved CR regardless of the type of prior intensive maintenance (HD-ara-C/m-AMSA/5-AZA or DNR/CD-ara-C). 3/23 (13%) pts died during hypoplasia, 2/23 (9%) pts were refractory to 2x ID-ara-C/m-AMSA. 3/23 pts died in CR during hypoplasia after intensive consolidation with HD-ara-C. Predictive factors for remission were the duration of preceding remission and the time from last chemotherapy to relapse. Three pts were transplanted in 2nd CR. 1/6 refractory pts reached CR, 2 pts remained refractory, and 3 died during hypoplasia. The median duration of disease-free survival (DFS) of relapsed pts was 3.3 months without further treatment, median survival of responding pts (18 replased pts, 1 refractory pt) was 4.6 months, the overall survival (n = 29) was 4.8 months. Pts receiving BMT were censured at the time of BMT. Seven pts experienced lung toxicity due to ara-C, four of whom died. The incidence of lung toxicity was clearly related to the extent of ara-C pretreatment during intensive maintenance. In conclusion, ID-ara-C/m-AMSA is a very effective reinduction treatment in these pts with acceptable toxicity; the impact of HD-ara-C during consolidation for DFS and survival is questionable.