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Overall survival in TP53-mutated AML and MDS.

Christian J Puzo1, Karl M Hager2, Henry M Rinder2

  • 1Yale School of Medicine, New Haven, CT, USA.

Annals of Hematology
|October 23, 2024
PubMed
Summary

TP53 mutations impact survival in AML and MDS. Updated 2022 guidelines classify these cases, but prognosis predictors remain unclear. This study found TP53 variant allele frequency and thrombocytopenia, not blast count, significantly predict overall survival.

Keywords:
AMLICCMDSMulti-hitTP53WHO

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Area of Science:

  • Hematology
  • Oncology
  • Genetics

Background:

  • TP53 mutations are common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), often indicating a poor prognosis.
  • Updated 2022 International Consensus Classification (ICC) and World Health Organization (WHO) guidelines classify p53-mutated AML/MDS.
  • The prognostic implications of TP53 mutations under these new guidelines, including co-mutations and their impact on overall survival (OS), require further investigation.

Purpose of the Study:

  • To evaluate the prognostic significance of TP53 mutations in AML and MDS patients based on the 2022 ICC and WHO classification criteria.
  • To identify key clinical and molecular predictors of overall survival (OS) in this patient cohort.

Main Methods:

  • Retrospective chart review of 210 AML or MDS patients with TP53 mutations identified via next-generation sequencing (NGS) at Yale New Haven Hospital (2015-2023).
  • Classification of patients according to the 2022 ICC and WHO guidelines.
  • Kaplan-Meier curves, log-rank testing, and Cox proportional hazards models were used to analyze the association between clinical/molecular data and OS.

Main Results:

  • Multi-hit TP53 mutations correlated with poorer OS in MDS (WHO: p=.02; ICC: p=.01) but not AML.
  • The strongest predictors of OS were platelet count < 50K (HR: 2.01) and TP53 variant allele frequency (VAF) ≤ 40% (HR: 0.68).
  • Blast count, complex karyotype, and specific TP53 mutation features did not show a significant association with OS.

Conclusions:

  • In a cohort classified by 2022 ICC/WHO criteria, TP53 VAF and thrombocytopenia are significant predictors of OS in AML/MDS.
  • These findings suggest that VAF and platelet count are more critical prognostic indicators than blast count or TP53 mutation characteristics.
  • The results underscore the utility of the updated criteria in identifying patients with aggressive disease biology and poor prognosis.