Transplant outcomes of the triple-negative NPM1/FLT3-ITD/CEBPA mutation subgroup are equivalent to those of the favourable ELN risk group, but significantly better than the intermediate-I risk group after allogeneic transplant in normal-karyotype AML

Ann Hematol. 2016 Mar;95(4):625-35. doi: 10.1007/s00277-015-2580-z. Epub 2015 Dec 22.

Abstract

The prognostic significance of molecular mutations (FLT3-ITD, NPM1, and CEBPA mutations) was examined in patients with normal-karyotype acute myeloid leukaemia (NK-AML) after allogeneic haematopoietic cell transplantation (HCT). In total, 115 patients received allogeneic HCT for NK-AML and were evaluated for FLT3-ITD, NPM1, and CEBPA mutations in diagnostic samples and for long-term outcomes following HCT, retrospectively. The prevalences of FLT3-ITD(pos), NPM1 (mut), and CEBPA (dm) (double mutations) were 32.2, 43.5, and 24.6 %, respectively. The triple-negative group (NPM1 (wild)/FLT3-ITD(neg)/non-CEBPA (dm)) showed a similar transplant outcome to those in the favourable European LeukemiaNet (ELN) risk group for overall survival (OS) (60.9 vs. 63.7 %; p = 0.810), but a more favourable OS than others in the intermediate-I risk group (40.0 %; p = 0.034). Also, the triple-negative group showed a similar relapse rate at 5 years compared with those in the favourable risk group (9.7 vs. 15.5 %; p = 0.499), but a lower rate of relapse than the others in the intermediate-I risk group (15.5 vs. 48.6 %; p = 0.004). The 5-year relapse incidences were 4.0 % (NPM1 (mut)/FLT3-ITD(neg)), 14.7 % (CEBPA (dm)), 15.5 % (NPM1 (wild)/FLT3-ITD(neg)/non-CEBPA (dm)), 39.1 % (NPM1 (mut)/FLT3-ITD(pos)/non-CEBPA (dm)), and 66.7 % (NPM1 (wild)/FLT3-ITD(pos)/non-CEBPA (dm)). Thus, the triple-negative (NPM1 (wild)/FLT3-ITD(neg)/non-CEBPA (dm)) group showed favourable long-term outcomes after allogeneic HCT in NK-AML, similar to those of the favourable risk group by the ELN risk classification.

Keywords: Acute myeloid leukaemia; Allogeneic haematopoietic cell transplantation; CEBPA; FLT3-ITD; NPM1; Normal karyotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • Europe / epidemiology
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation / mortality
  • Hematopoietic Stem Cell Transplantation / trends*
  • Humans
  • Karyotype
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Nuclear Proteins / genetics*
  • Nucleophosmin
  • Retrospective Studies
  • Risk Factors
  • Survival Rate / trends
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

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