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

Haematologica. 1997 Nov-Dec;82(6):660-3.

Abstract

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 < 0.5 x 10(9)/L or moderate neutropenia with infectious episodes, platelets < 30 x 10(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/m2/day i.v. 6-hour infusion, on days 1-4, IDA 10 mg/m2/day i.v., on days 1-3. Elderly patients (> or = 65 yrs) were treated with lower doses: Ara-C 1 g/m2/day 6 hours infusion, on days 1 and 2, IDA 10 mg/m2/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 > or = 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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cytarabine / administration & dosage
  • Female
  • Humans
  • Idarubicin / administration & dosage
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Remission Induction / methods
  • Risk Factors

Substances

  • Cytarabine
  • Idarubicin