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<p>Relapse of acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation (allo-HCT) remains a life-threatening complication and is influenced by the underlying biology of the AML and possibly by genetic alterations. In this retrospective multicenter study, we evaluated mutational dynamics of AML cells in 57 patients with relapse after allo-HCT. We observed that 68% of patients exhibited genetic instability, characterized by acquisition or loss of mutations, most frequently involving <i>FLT3-ITD, NRAS</i>, and <i>KRAS</i>, while founding lesions such as <i>DNMT3A</i> were usually retained. Clonal evolution patterns varied, with constant profiles (35.0%), linear (29.8%), branching (22.8%), and parallel (12.3%) evolution. However, these evolutionary categories were not associated with differences in progression-free or overall survival. In contrast, relapse timing was highly prognostic: early relapse ( ≤ 6 months) conferred a significant higher mortality risk compared to late relapse, independent of evolution model. Our findings indicate that while relapse after allo-HCT in AML is genetically diverse, timing of recurrence remains the most critical determinant of outcome. Given that certain genetic changes may inform therapeutic options, these findings highlight the relevance of longitudinal molecular monitoring especially during the early post-transplant period.</p>

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Mutational landscape changes of AML in patients relapsing after allogeneic hematopoietic cell transplantation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月3日

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  • Kristina Maas-Bauer,
  • Thomas Meyer,
  • Mehtap Yücel,
  • Maria Garofalaki,
  • Stefanie Koßmann,
  • Francesca Biavasco,
  • Memnon Lysandrou,
  • Miguel Waterhouse,
  • Tobias Feuchtinger,
  • Dietmar Pfeifer,
  • Florian Ingelfinger,
  • Tobias Wertheimer,
  • Justus Duyster,
  • Jae Sook Ahn,
  • Robert J. Soiffer,
  • Jürgen Finke,
  • Ralph Wäsch,
  • Alexandros Spyridonidis,
  • Dennis Dong Hwan Kim,
  • Claudia Wehr,
  • Robert Zeiser

摘要

Relapse of acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation (allo-HCT) remains a life-threatening complication and is influenced by the underlying biology of the AML and possibly by genetic alterations. In this retrospective multicenter study, we evaluated mutational dynamics of AML cells in 57 patients with relapse after allo-HCT. We observed that 68% of patients exhibited genetic instability, characterized by acquisition or loss of mutations, most frequently involving FLT3-ITD, NRAS, and KRAS, while founding lesions such as DNMT3A were usually retained. Clonal evolution patterns varied, with constant profiles (35.0%), linear (29.8%), branching (22.8%), and parallel (12.3%) evolution. However, these evolutionary categories were not associated with differences in progression-free or overall survival. In contrast, relapse timing was highly prognostic: early relapse ( ≤ 6 months) conferred a significant higher mortality risk compared to late relapse, independent of evolution model. Our findings indicate that while relapse after allo-HCT in AML is genetically diverse, timing of recurrence remains the most critical determinant of outcome. Given that certain genetic changes may inform therapeutic options, these findings highlight the relevance of longitudinal molecular monitoring especially during the early post-transplant period.