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<p>Acute myeloid leukemia (AML) includes genetically defined subsets. In allogeneic hematopoietic cell transplantation (allo-HCT), the frequency and prognosis of gene-gene interactions may differ from those of patients treated with chemotherapy alone. In this study, adult patients (<i>N</i> = 952) with AML allografted between 2015 and 2023, with available next generation sequencing (NGS) at diagnosis were included. Most frequent mutations were <i>DNMT3A (24%), FLT3-</i>ITD <i>(21%), NPM1 (21%), RUNX1 (16%), NRAS (16%), TET2 (14%)</i>, and <i>IDH2 (12%)</i>. Multiple correspondence analysis identified distinct groups of co-occurring mutations. Outcome analysis was performed on 646 AML patients allografted in first complete remission (CR1). Six non-overlapping groups were constructed: 1) <i>TP53</i> mutation (<i>N</i> = 47); 2) <i>NPM1</i> mutation (<i>N</i> = 129); 3) <i>FLT3</i>-ITD and/or <i>DNMT3A</i> mutation (<i>N</i> = 128); 4) <i>SRSF2</i> and/or <i>ASXL1</i> and/or <i>RUNX1</i> mutation (SAR group) (<i>N</i> = 132); 5) <i>IDH1</i> and/or <i>IDH2</i> and/or <i>TET2</i> mutation (<i>N</i> = 43); and 6) all ten genes unmutated (<i>N</i> = 167). In multivariable analysis, <i>TP53</i> mutation, adverse karyotype, and age negatively affected leukemia-free survival (LFS) and overall survival (OS). OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.</p>

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Frequency and impact of somatic co-occurring mutations on post-transplant outcomes in acute myeloid leukemia: a multicenter registry analysis on behalf of the EBMT ALWP

  • 期刊论文

  • 发表日期：

    2025年12月5日

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  • Ali Bazarbachi,
  • Jacques-Emmanuel Galimard,
  • Iman Abou Dalle,
  • Myriam Labopin,
  • Jaime Sanz,
  • He Huang,
  • Jiri Mayer,
  • Carlos Solano,
  • Bruno Lioure,
  • Laimonas Griskevicius,
  • Johan Maertens,
  • Maija Itälä-Remes,
  • Ain Kaare,
  • Maria-Pilar Gallego-Hernanz,
  • Gesine Bug,
  • Josep-Maria Ribera,
  • Alain Gadisseur,
  • Christoph Schmid,
  • Mi Kwon,
  • Xavier Poiré,
  • Paola Coccia,
  • Manuel Jurado Chacón,
  • Frédéric Baron,
  • Charles Craddock,
  • Eolia Brissot,
  • Arnon Nagler,
  • Fabio Ciceri,
  • Mohamad Mohty

摘要

Acute myeloid leukemia (AML) includes genetically defined subsets. In allogeneic hematopoietic cell transplantation (allo-HCT), the frequency and prognosis of gene-gene interactions may differ from those of patients treated with chemotherapy alone. In this study, adult patients (N = 952) with AML allografted between 2015 and 2023, with available next generation sequencing (NGS) at diagnosis were included. Most frequent mutations were DNMT3A (24%), FLT3-ITD (21%), NPM1 (21%), RUNX1 (16%), NRAS (16%), TET2 (14%), and IDH2 (12%). Multiple correspondence analysis identified distinct groups of co-occurring mutations. Outcome analysis was performed on 646 AML patients allografted in first complete remission (CR1). Six non-overlapping groups were constructed: 1) TP53 mutation (N = 47); 2) NPM1 mutation (N = 129); 3) FLT3-ITD and/or DNMT3A mutation (N = 128); 4) SRSF2 and/or ASXL1 and/or RUNX1 mutation (SAR group) (N = 132); 5) IDH1 and/or IDH2 and/or TET2 mutation (N = 43); and 6) all ten genes unmutated (N = 167). In multivariable analysis, TP53 mutation, adverse karyotype, and age negatively affected leukemia-free survival (LFS) and overall survival (OS). OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.