Allogeneic hematopoietic stem cell transplantation could improve survival of cytogenetically normal adult acute myeloid leukemia patients with DNMT3A mutations

Am J Hematol. 2015 Nov;90(11):992-7. doi: 10.1002/ajh.24135.

Abstract

DNMT3A mutations are frequent in cytogenetically normal acute myeloid leukemia (cn-AML) patients and associated with poor survival. The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in DNMT3A(mut) cn-AML patients remains unclear. In this study, we retrospectively analyzed the prognostic impact of DNMT3A mutations and explored the role of allo-HSCT in 308 cn-AML patients who received consolidation of intensive chemotherapy or allo-HSCT in our center from March 2005 to May 2014. In the whole cohort, 63 patients (20.5%) were identified with DNMT3A exon 23 mutations and R882H was the most frequent variant. DNMT3A(mut) patients had shorter overall survival (3-year OS: 31.9% vs. 52.0%, P = 0.009) and disease-free survival (3-year DFS: 21.8% vs. 40.1%, P = 0.004) compared with DNMT3A(wt) patients. Based on FLT3/NPM1/CEBPA mutations, 308 cn-AML patients were divided into favorable/intermediate group (n = 262) and unfavorable group (n = 46). There were no significant differences in 3-year OS and 3-year DFS between DNMT3A(mut) and DNMT3A(wt) patients in both favorable/intermediate and unfavorable groups. Additionally, in multivariate analysis, DNMT3A mutation remained an independent adverse prognostic factor for the survival. In the DNMT3A(mut) cohort, 23 complete remission (CR) patients received allo-HSCT consolidation and 32 CR patients received chemotherapy consolidation, dramatic differences were observed in 3-year OS (51.7% vs. 28.9%, P = 0.048) and 3-year DFS (41.6% vs. 14.9%, P = 0.024) between allo-HSCT group and chemotherapy group. Collectively, DNMT3A mutation is a poor prognostic factor for cn-AML patients and allo-HSCT could improve survival of cn-AML patients with DNMT3A mutations.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Cytogenetic Analysis
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methyltransferase 3A
  • Female
  • Gene Expression
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation*
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Prognosis
  • Remission Induction
  • Retrospective Studies
  • Survival Analysis
  • Transplantation, Homologous
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Antineoplastic Agents
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • DNMT3A protein, human
  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3