5-Azacytidine treatment for relapsed or refractory acute myeloid leukemia after intensive chemotherapy

Am J Hematol. 2013 Jul;88(7):601-5. doi: 10.1002/ajh.23464. Epub 2013 May 30.

Abstract

Despite progress in the understanding of leukemia pathophysiology, the treatment of acute myeloid leukemia (AML) remains challenging. In patients with refractory or relapsed (R/R) AML, the prognosis is still poor and this group is targeted for new drug development. We reviewed the outcome of 47 patients, with R/R AML after at least one course of intensive chemotherapy, treated with 5-azacytidine in three different French institutions. The overall response rate was 38% including complete remission in 21%, partial remission in 11%, and hematological improvement in 6% of cases. Median time to relapse was 6 (range, 1-39) months. Median overall survival was 9 months (not reached by responders vs. 4.5 months for nonresponders patients, P = 0.0001). Univariate analysis identified the absence of peripheral blood blasts and <20% bone marrow blasts as prognostic factors for both overall response and survival, but not age, ECOG/PS, type of AML, cytogenetic, status of the disease, number of previous lines of therapy, previous hematological stem cell transplantation, or white blood cells count. Bone marrow blasts percentage <20% was the only independent prognostic factor identified by multivariate analysis for overall response (P = 0.0013) and survival (P = 0.0324). Six patients in remission could proceed to an allogenic hematological stem cell transplantation. The drug-related grade 3/4 adverse events were hematopoietic toxicities (38%) and infection (32%). In conclusion, this study suggests that a salvage therapy with 5-azacytidine is an interesting option for patients with R/R AML after intensive chemotherapy. Prospective randomized studies are needed to demonstrate a superiority of this approach over others strategies.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols*
  • Azacitidine / therapeutic use*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / pathology
  • Chromosome Aberrations
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Recurrence
  • Remission Induction
  • Retrospective Studies
  • Salvage Therapy / methods*
  • Survival Analysis
  • Treatment Outcome
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Antimetabolites, Antineoplastic
  • Nuclear Proteins
  • Nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • Azacitidine