Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3-ITD molecular status for cytogenetically normal AML patients: a GOELAMS study

Am J Hematol. 2012 Dec;87(12):1052-6. doi: 10.1002/ajh.23311. Epub 2012 Aug 22.

Abstract

The choice of postremission therapy for acute myeloid leukemia (AML) patients is now based on the blasts' cytogenetic and molecular profile. However, the potential benefit of autologous hematopoietic stem cell transplantation (auto-HSCT) according to the NPM1/FLT3-ITD status has been poorly studied in AML patients with a normal karyotype (NK). Therefore, we evaluated the NPM1/FLT3-ITD molecular status in 135 NK-AML patients treated by allogeneic HSCT (allo-HSCT), auto-HSCT, or chemotherapy as consolidation therapy within the GOELAMS LAM-2001 trial. In univariate analyzes, 4-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher for NPM1+/FLT3-ITD- patients compared with patients presenting another molecular profile (61 vs. 43% and 72 vs. 48%, P = 0.02 and P = 0.01, respectively). In the NPM1+/FLT3-ITD- subgroup, there was no benefit for allo-HSCT or auto-HSCT vs. chemotherapy (4-year LFS: 71, 56, and 60%; 4-year OS: 73, 71, and 60%, respectively; P = NS). For patients with other NPM1/FLT3-ITD molecular profiles, allo-HSCT was found to be the best consolidation therapy, whereas auto-HSCT was associated with a better outcome when compared with chemotherapy (allo-HSCT-, auto-HSCT-, and chemotherapy-related 4-year LFS: 68, 44, and 36%, P = 0.004; 4-year OS: 68, 52, and 29%, respectively, P = 0.02). Our study indicates that allo-HSCT and auto-HSCT provide similar outcomes compared with chemotherapy as consolidation for NPM1+/FLT3-ITD- NK-AML patients. For NK-AML patients with an adverse molecular profile, auto-HSCT could represent an alternative therapeutic approach when no human leukocyte antigen-matched allogeneic donor is available.

Trial registration: ClinicalTrials.gov NCT01015196.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Cytogenetics
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / surgery*
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Nucleophosmin
  • Retrospective Studies
  • Transplantation, Autologous
  • Treatment Outcome
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics*
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3

Associated data

  • ClinicalTrials.gov/NCT01015196