Journal Article

Allogenic Stem Cell Transplantation Abrogates Negative Impact on Outcome of AML Patients with KMT2A Partial Tandem Duplication

Boureau, Lisa, Bidet, Audrey, Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL] ; Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS) ; Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Agroécologie [Dijon] ; Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Thomas, Xavier, Ghesquières, Hervé, Huet, Sarah, Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux), Antherieu, Gabriel, Immuno-Biologie des Lymphomes [CIRI] (CIRI-LIB) ; Centre International de Recherche en Infectiologie (CIRI) ; École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Nati

2021

Overview

Recently, a new subset of acute myeloid leukemia (AML) presenting a direct partial tandem duplication (PTD) of the KMT2A gene was described. The consequences of this alteration in terms of outcome and response to treatment remain unclear. We analyzed retrospectively a cohort of KMT2A-PTD-mutated patients with newly diagnosed AML. With a median follow-up of 3.6 years, the median overall survival was 12.1 months. KMT2A-PTD-mutated patients were highly enriched in mutations affecting epigenetic actors and the RTK/RAS signaling pathway. Integrating KMT2A-PTD in ELN classification abrogates its predictive value on survival suggesting that this mutation may overcome other genomic marker effects. In patients receiving intensive chemotherapy, hematopoietic stem cell transplantation (HSCT) significantly improved the outcome compared to non-transplanted patients. In the multivariate analysis, only HSCT at any time in complete remission (HR = 2.35; p = 0.034) and FLT3-ITD status (HR = 0.29; p = 0.014) were independent variables associated with overall survival, whereas age was not. In conclusion, our results emphasize that KMT2A-PTD should be considered as a potential adverse prognostic factor. However, as KMT2A-PTD-mutated patients are usually considered an intermediate risk group, upfront HSCT should be considered in first CR due to the high relapse rate observed in this subset of patients.

• Publisher: MDPI,CCSD,MDPI AG
• Subject: Acute myeloid leukemia / Blood / Chemotherapy / Classification / Disease / DNA methylation / Epigenetics / Gene expression / Genomics / Hematopoietic stem cells / Kinases / Leukemia / Life Sciences / Medical prognosis / MLL protein / Multivariate analysis / Mutation / Myeloid leukemia / Patients / Remission / Signal transduction / Stem cell transplantation / Stem cells / Transplants & implants