Fludarabine and cytarabine versus high-dose cytarabine in consolidation treatment of t(8; 21) acute myeloid leukemia: A prospective, randomized study

Am J Hematol. 2017 Jan;92(1):12-17. doi: 10.1002/ajh.24569. Epub 2016 Oct 21.

Abstract

Acute myeloid leukemia (AML) patients with t(8;21) aberration often have favorable outcomes, however, relapse still occurs in 30-40% patients, with only 50-60% of patients with t(8;21) AML cured with regimens containing high-dose cytarabine (HD-Ara-C). To evaluate the effects of fludarabine and cytarabine (FA) consolidation therapy for t(8;21) AML patients, a prospective randomized study was performed. A total of 45 patients with t(8;21) AML after achieving complete remission (CR) were randomly assigned to receive four course consolidation with FA (n = 23) or HD-Ara-C (n = 22). Our study showed that at 36-months, relapse-free survival (RFS) was 81.73% in the FA arm and 50.73% in the HD-Ara-C arm (P = 0.04), overall survival (OS) was 91.1% and 48.4% (P = 0.01) in the FA arm and in the HD-Ara-C arm respectively; whereas cumulative incidence of relapse (CIR) was 18.27% and 47.39%, in the FA arm and in the HD-Ara-C arm respectively (P = 0.05). In our study, treatment with FA, MRD2 status (reduction ≥ 3-log) and absence of c-kit mutations were identified as independent prognostic factors for lower risk of relapse, improved RFS and OS. We also found RFS for patients without c-kit mutations was 100% in FA arm, and 57.8% in HD-Ara-C arm at 36 months (P = 0.005); OS of both groups at 36 months was 100% and 51.4%, respectively (P = 0.004), suggesting a benefit of consolidation therapy with FA for t(8;21) AML patients, especially, those without c-kit mutations (Clinicaltrials.org ID NCT# 02024308). Am. J. Hematol. 92:12-17, 2017. © 2016 Wiley Periodicals, Inc.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chromosomes, Human, Pair 21 / genetics*
  • Chromosomes, Human, Pair 8 / genetics*
  • Consolidation Chemotherapy
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Cytarabine / therapeutic use*
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / mortality
  • Middle Aged
  • Mutation
  • Prospective Studies
  • Proto-Oncogene Proteins c-kit / genetics
  • Translocation, Genetic
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use
  • Young Adult

Substances

  • Cytarabine
  • Proto-Oncogene Proteins c-kit
  • Vidarabine
  • fludarabine