FLT3-ITD and CEBPA Mutations Predict Prognosis in Acute Myelogenous Leukemia Irrespective of Hematopoietic Stem Cell Transplantation

Biol Blood Marrow Transplant. 2019 May;25(5):941-948. doi: 10.1016/j.bbmt.2018.11.031. Epub 2018 Nov 29.

Abstract

Cytogenetic and genetic changes have prognostic significance in acute myelogenous leukemia (AML). In our study, we compared the cytogenetic changes and gene mutations (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) with clinical outcomes in 1132 patients with AML enrolled at our center over a 10-year period. A total of 977 patients provided gene mutation data. There were subsets of patients who exhibited mutations in NPM1 (17.9%), CEBPA (16.4%), FLT3-ITD (18.5%), FLT3-TKD (3.9%), DNMT3A (8.6%), and C-KIT (8.8%). A total of 557 patients (49.2%) underwent hematopoietic stem cell transplantation (HSCT) as consolidation therapy. Multivariate analysis identified an adverse karyotype (hazard ratio [HR], 1.48; P = .001), the presence of FLT3-ITD (HR, 1.90; P < .001), and receipt of nonstandard first-line induction chemotherapy (HR, 1.45; P = .003) as significant risk factors for poor overall survival (OS), and the presence of CEBPAmut (HR, .42; P < .001) and receipt of HSCT (HR, .35; P < .001) as prognostic factors for favorable OS. In addition, the presence of FLT3-ITDmut (HR, 2.11; P < .001) was identified as an independent risk factor for poor disease-free survival (DFS), and receipt of HSCT was correlated with improved DFS (HR, .74; P = .046). Compared with chemotherapy as consolidation therapy, HSCT improved the prognosis and overcame the prognostic effect of karyotype from the initial diagnosis; however, the presence of FLT3-ITD or CEBPA mutation can predict prognosis in AML irrespective of HSCT.

Keywords: Acute myelogenous leukemia; CEBPA; FLT3-ITD; Hematopoietic stem cell transplantation; Mutation; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • Disease-Free Survival
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Mutation*
  • Nucleophosmin
  • Prognosis
  • Remission Induction / methods
  • Risk Factors
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

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