Predictive significance of the European LeukemiaNet classification of genetic aberrations in patients with acute myeloid leukaemia undergoing allogeneic stem cell transplantation

Eur J Haematol. 2017 Feb;98(2):160-168. doi: 10.1111/ejh.12815. Epub 2016 Oct 22.

Abstract

Objectives: The purpose of this study was to evaluate the predictive capacity of the European LeukemiaNet (ELN) classification of genetic risk in patients with acute myeloid leukaemia (AML) undergoing allogeneic stem cell transplantation (alloSCT).

Methods: We retrospectively analysed 274 patients transplanted at our centre between 2004 and 2014.

Results: The ELN grouping is comparable to the Southwest Oncology Group/Eastern Cooperative Oncology Group (SWOG/ECOG) stratification in predicting the outcome after alloSCT [overall P = 0.0064 for disease-free survival (DFS), overall P = 0.003 for relapse]. Patients with an intermediate-1 profile have a significantly elevated 5-yr relapse incidence as compared to favourable risk patients, that is 40% vs. 15%, [hazard ratio (HR) 2.58, P = 0.048]. An intermediate-1 risk profile is an independent predictor for relapse as determined by multivariate Cox regression analysis (HR 3.05, P = 0.023). In intermediate-1 patients, the presence of an FLT3 internal tandem duplication (FLT3-ITD) is associated with a significantly increased relapse incidence (P = 0.0323), and a lower DFS (P = 0.0465). FLT3-ITD is an independent predictor for overall survival, DFS and relapse incidence in the intermediate-1 subgroup.

Conclusions: The ELN stratification of genetic risk predicts the outcome of patients with AML undergoing alloSCT. Patients with an intermediate-1 profile have a high risk for treatment failure due to relapse, which prompts the development of alternative treatment strategies.

Keywords: European LeukemiaNet; FLT3 internal tandem duplication; acute myeloid leukaemia; allogeneic stem cell transplantation; karyotype.

MeSH terms

  • Adolescent
  • Adult
  • Combined Modality Therapy
  • Female
  • Genetic Variation*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Recurrence
  • Retrospective Studies
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Treatment Failure
  • Treatment Outcome
  • Young Adult