Prognostic significance of persisting DNMT3A, ASXL1, and TET2 mutation burden in acute myeloid leukemia patients with allogeneic hematopoietic stem cell transplantation during complete remission

Leuk Lymphoma. 2024 Mar;65(3):363-371. doi: 10.1080/10428194.2023.2284089. Epub 2023 Nov 22.

Abstract

We retrospectively analyzed 155 AML patients with DAT mutations at diagnosis who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at complete remission. Of the 155 AML patients with DAT mutations at diagnosis, 59 (38.1%) patients had persisting DAT mutations pretransplantation. Compared to patients with pretransplant DAT transitions, patients with persisting DAT mutation burden were shown to be older (p = 0.004), and fewer patients had TET2 mutations at diagnosis (p = 0.033). Patients with persistent DAT mutation burden had shorter overall survival (OS) (3-year OS: 59.3% vs. 83.0%, p < 0.001) and disease-free survival (DFS) (3-year DFS: 56.1% vs. 83.0%, p < 0.001) with a higher cumulative incidence of relapse (CIR) (24.6% vs. 17.4%, p = 0.002) than those with DAT transitions. Additionally, multivariate analysis confirmed that persisting DAT mutations were an independent adverse factor for relapse, OS, and DFS. Collectively, persisting DAT mutations prior to allo-HSCT at complete remission for AML correlated with negative outcomes.

Keywords: ASXL1 mutations; DNMT3A mutations; TET2 mutations; acute myeloid leukemia; allogeneic hematopoietic stem cell transplantation.

MeSH terms

  • DNA-Binding Proteins / genetics
  • Dioxygenases* / genetics
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / therapy
  • Mutation
  • Pathologic Complete Response
  • Prognosis
  • Recurrence
  • Repressor Proteins / genetics
  • Retrospective Studies
  • Transcription Factors / genetics

Substances

  • Transcription Factors
  • ASXL1 protein, human
  • Repressor Proteins
  • TET2 protein, human
  • DNA-Binding Proteins
  • Dioxygenases