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<p>Mutations in the DNMT3A gene are not yet classified as a distinct prognostic group in the latest European Leukemia Net (ELN) 2022 genetic risk classification of AML. We analyzed 1888 adult AML patients with ELN 2022 intermediate- or poor-risk cytogenetics who received their first allo-transplant in first complete remission between 2015 and 2022. Among patients with cytogenetically normal AML, the triple-positive mutation group (<i>DNMT3A</i>, <i>NPM</i>1, and <i>FLT3</i>-ITD) was the most frequent (<i>n</i> = 340, 29%), while <i>DNMT3A</i> co-occurrence with either <i>FLT3</i> or <i>NPM1</i> mutations alone was less common (4% and 9%, respectively). Patients with <i>DNMT3A</i> mutations were less likely to have a secondary AML (14% versus 24%, <i>p </i>&lt; 0.001). <i>DNMT3A</i> mutations negatively affected post-transplant leukemia-free survival (LFS) in patients with normal karyotype and <i>NPM1</i> mutation without <i>FLT3</i>-ITD (2-year LFS: 70% versus 90%, hazard ratio [HR]: 3.3, <i>p</i> = 0.006), and increased relapse incidence (RI) in <i>FLT3</i>-ITD and wild-type <i>NPM1</i> subgroup (2-year RI: 30% versus 18%, HR: 2.32, <i>p</i> = 0.03). Notably, patients with normal karyotype and triple-positive mutation exhibited excellent 2-year LFS and OS (61% and 70%), indicating that allo-transplant overcomes the dismal outcome of this group. The impact of <i>DNMT3A</i> mutations on post-transplant outcomes in AML patients in first remission varies based on karyotype and co-mutations.</p>

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The impact of DNMT3A mutation on survival of AML patients receiving allotransplant in first remission depends on the karyotype and co-occurring mutations

  • 期刊论文

  • 发表日期：

    2025年12月23日

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  • Iman Abou Dalle,
  • Jacques-Emmanuel Galimard,
  • Xavier Poire,
  • Jaime Sanz,
  • Anne Huynh,
  • Nicolaus Kröger,
  • Eva Maria Wagner-Drouet,
  • David Burns,
  • Matthias Eder,
  • Bruno Lioure,
  • Depei Wu,
  • Jiri Mayer,
  • Kristina Carlson,
  • Matthias Stelljes,
  • Matthew Collin,
  • Mahmoud Aljurf,
  • Arnon Nagler,
  • Jordi Esteve,
  • Fabio Ciceri,
  • Ali Bazarbachi,
  • Mohamad Mohty

摘要

Mutations in the DNMT3A gene are not yet classified as a distinct prognostic group in the latest European Leukemia Net (ELN) 2022 genetic risk classification of AML. We analyzed 1888 adult AML patients with ELN 2022 intermediate- or poor-risk cytogenetics who received their first allo-transplant in first complete remission between 2015 and 2022. Among patients with cytogenetically normal AML, the triple-positive mutation group (DNMT3A, NPM1, and FLT3-ITD) was the most frequent (n = 340, 29%), while DNMT3A co-occurrence with either FLT3 or NPM1 mutations alone was less common (4% and 9%, respectively). Patients with DNMT3A mutations were less likely to have a secondary AML (14% versus 24%, p < 0.001). DNMT3A mutations negatively affected post-transplant leukemia-free survival (LFS) in patients with normal karyotype and NPM1 mutation without FLT3-ITD (2-year LFS: 70% versus 90%, hazard ratio [HR]: 3.3, p = 0.006), and increased relapse incidence (RI) in FLT3-ITD and wild-type NPM1 subgroup (2-year RI: 30% versus 18%, HR: 2.32, p = 0.03). Notably, patients with normal karyotype and triple-positive mutation exhibited excellent 2-year LFS and OS (61% and 70%), indicating that allo-transplant overcomes the dismal outcome of this group. The impact of DNMT3A mutations on post-transplant outcomes in AML patients in first remission varies based on karyotype and co-mutations.