Azacitidine treatment for patients with myelodysplastic syndrome and acute myeloid leukemia with chromosome 3q abnormalities

Am J Hematol. 2015 Oct;90(10):859-63. doi: 10.1002/ajh.24099. Epub 2015 Jul 14.

Abstract

Acute Myeloid Leukemia (AML) and myelodysplasia (MDS) with chromosome 3q abnormalities have a dismal outcome either untreated or with conventional treatments. Azacitidine (AZA) is now considered as the standard of care in high-risk MDS and oligoblastic AML patients. The objective of this study was to evaluate the impact of azacitine treatment in this cytogenetic subgroup. We report here a multicentre retrospective study of 157 patients treated with AZA for AML/MDS with chromosome 3q abnormalities and 27 patients with isolated EVI-1 overexpression. Median age was 65 years, 40 patients (25%) had inv(3)(q21q26.2) or t(3;3)(q21;q26.2), 36 patients (23%) had other balanced 3q26 rearrangements, 8 patients (5%) had balanced 3q21 rearrangements and 73 patients (46%) had other 3q abnormalities. The overall response rate was 50% (29% CR). Median overall survival was 10.6 months. By multivariate analysis, patients with lower bone marrow blast counts, higher platelet counts, non-complex cytogenetics, and absence of prior treatment with intensive chemotherapy had a better outcome. 27 patients were allo-transplanted and achieved a 21-month median OS. Balanced 3q21 translocations were associated with a better response rate and overall survival. Outcome of patients with isolated EVI-1 overexpression was comparable to that of patients with chromosome 3q lesions. Thus, AML/MDS patients with 3q abnormalities appear to be a heterogeneous group in their response to AZA, and AZA may represent a suitable option in particular as a bridge to allogeneic transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Allografts
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Azacitidine / administration & dosage*
  • Blast Crisis* / genetics
  • Blast Crisis* / mortality
  • Blast Crisis* / therapy
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 3 / genetics*
  • Disease-Free Survival
  • Female
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / mortality
  • Leukemia, Myeloid, Acute* / therapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes* / genetics
  • Myelodysplastic Syndromes* / mortality
  • Myelodysplastic Syndromes* / therapy
  • Retrospective Studies
  • Stem Cell Transplantation
  • Survival Rate

Substances

  • Antimetabolites, Antineoplastic
  • Azacitidine