Idarubicin and cytosine arabinoside in the induction and maintenance therapy of high-risk myelodysplastic syndromes

Background and Objective. Recently, the results of some pilot studies have shown the efficacy of the association of idarubicin (IDA) and cytosine arabinoside (Ara-C), already successfully employed in acute myeloid leukemia (AML), for remission induction in patients with myelodysplastic syndrome (MDS). We set out to evaluate in a multicenter study the efficacy and tolerability of an intensive therapy with IDA and Ara-C in patients with RAEB and RAEB-t, the rate and duration of complete remission, and the overall survival in adults treated with full doses and in the elderly treated with lower doses; furthermore, we investigated the efficacy of low-dose maintenance chemotherapy. Methods. Pretreated adult patients with de novo RAEB and RAEB-t, meeting at least one of the following criteria, were included: neutrophils <0.5x10(9)/L or moderate neutropenia with infectious episodes, platelets <30x10(9)/L or moderate thrombocytopenia with bleeding symptoms, transfusion >4 red cell units/months, rapid increase of bone marrow blasts. Induction treatment consisted of a cycle with IDA and Ara-C. Adult patients less than 65 years old were treated with the following doses: Ara-C 1 g/m(2)/day i.v. 6-hour infusion, on days 1-4, IDA 10 mg/m(2)/day i.v., on days 1-3. Elderly patients (greater than or equal to 65 yrs) were treated with lower doses: Ara-C 1 g/m(2)/day 6 hours infusion, on days 1 and 2, IDA 10 mg/m(2)/day i.v., on days 1 and 2. Responders followed a consolidation course identical to induction. Results, From February 1994 to February 1997, 25 patients were enrolled, 20 males and 5 females aged between 22 and 76, 10 were greater than or equal to 65 years old, 7 had RAEB and 18 had RAEB-t. Twelve cases (48%) achieved complete remission (CR), 7 cases (28%) achieved partial remission, 4 patients were resistant and two patients (8%) died during the aplastic phase. A significantly higher CR rate was found in younger patients (p = 0.036), while gender, FAB subtype, presence of Auer rods, cytogenetic findings, and the interval from diagnosis to treatment did not significantly influence CR achievement, Interpretation and Conclusions. Our results show that in de novo RAEB and RAEB-t, treatment with IDA and Ara-C is associated with satisfactory frequency of response with acceptable toxicity. (C) 1997, Ferrata Storti Foundation.