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Prognostic implication of gene mutations on overall survival in the adult acute myeloid leukemia patients receiving or not receiving allogeneic hematopoietic stem cell transplantations

Leukemia Research

Highlights

 

  • We evaluate prognostic impact of mutations in AML patients receiving allo-HSCT.
  • FLT3-ITD and mutation ofNPM1do not affect the outcome.
  • CEBPAdouble muthas a trend to be an independent good prognostic factor.
  • Surprisingly,RUNX1mutation is an independent good prognostic factor.

Abstract

Several gene mutations have been shown to provide clinical implications in patients with acute myeloid leukemia (AML). However, the prognostic impact of gene mutations in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We retrospectively evaluated the clinical implications of 8 gene mutations in 325 adult AML patients; 100 of them received allo-HSCT and 225 did not. The genetic alterations analyzed includedNPM1, FLT3-ITD, FLT3-TKD, CEBPA, RUNX1, RAS, MLL-PTD, andWT1. In patients who did not receive allo-HSCT, older age, higher WBC count, higher lactate dehydrogenase level, unfavorable karyotype, andRUNX1mutation were significantly associated with poor overall survival (OS), whileCEBPAdouble mutation (CEBPAdouble-mut) andNPM1mut/FLT3-ITDnegwere associated with good outcome. However, in patients who received allo-HSCT, only refractory disease status at the time of HSCT and unfavorable karyotype were independent poor prognostic factors. Surprisingly,RUNX1mutation was an independent good prognostic factor for OS in multivariate analysis. The prognostic impact ofFLT3-ITD orNPM1mut/FLT3-ITDnegwas lost in this group of patients receiving allo-HSCT, whileCEBPAdouble-mutshowed a trend to be a good prognostic factor. In conclusion, allo-HSCT can ameliorate the unfavorable influence of some poor-risk gene mutations in AML patients. Unexpectedly, theRUNX1mutation showed a favorable prognostic impact in the context of allo-HSCT. These results need to be confirmed by further studies with more AML patients.

Keywords: Acute myeloid leukemia, Gene mutations, Allogeneic hematopoietic stem cell transplantation.

Footnotes

a Division of Hematology, Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

b Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

c National Taiwan University Hospital, Taipei, Taiwan, Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

lowast Corresponding authors. Tel.: +886 2 33668188x111; fax: +886 2 33668190.

1 H.-F. Tien and S-C. Chou contributed equally to this research work.