Prognostic implication of molecular aberrations in cytogenetically normal acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation

Genet Mol Res. 2013 Nov 11;12(4):5414-23. doi: 10.4238/2013.November.11.3.

Abstract

Different molecular aberrations can be discriminated into certain prognostic subgroups in cytogenetically normal acute myeloid leukemia (CN-AML) patients but their impact on allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains controversial and studies from Asian populations are lacking. Forty-two adult non-M3 AML patients receiving allo-HSCT from 2002 to 2009 in southern Taiwan were retrospectively reviewed for survey, 23 (54.7%) of whom were CN-AML. NPM1, FLT3-ITD, and CEBPA were analyzed. After a median follow-up of 104 weeks (range, 8 to 384), patients in the good risk group (harboring either NPM1 or CEBPA mutation without concurrent FLT3-ITD) showed a borderline worse overall survival (OS) compared with the intermediate/poor risk group (P = 0.08). Interestingly, a poorer OS was found in patients with the CEBPA mutation (P = 0.003) but not the NPM1 mutation (P = 0.96). No OS difference was found between patients with or without FLT3-ITD (P = 0.15). In patients receiving allo-HSCT at first remission, there was no significant OS benefit in the good risk group (P = 0.33). In patients receiving allo-HSCT beyond first remission, disease status played a major role (P = 0.006), irrespective of molecular aberrations. Allo-HSCT in good risk patients should be carefully evaluated in Taiwanese, especially in patients with the CEBPA mutation. Conversely, allo-HSCT should be considered in first remission in patients with an intermediate/poor risk, where it may overcome the adverse impact of FLT3-ITD. Disease status remained a main issue in patients receiving allo-HSCT beyond first remission.

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics*
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / surgery
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics*
  • Nucleophosmin
  • Prognosis
  • Treatment Outcome
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • Biomarkers, Tumor
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3