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<p>Allogeneic hematopoietic stem cell transplantation is recommended for <i>TP53</i>-mutant acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) despite a high relapse rate and poor survival. To understand <i>TP53</i> alterations on a molecular level and define stratified prognostic outcomes following transplantation, we performed targeted next-generation sequencing on 63 patients who underwent transplantation for <i>TP53</i>-mutant AML/MDS and profiled their molecular spectrum. Sixty-eight <i>TP53</i> mutations were detected, with a median variant allele frequency of 46.8%. Copy number alterations at the <i>TP53</i> locus were present in 19 patients (30%). Complex karyotype was detected in 48 patients (76%) and was significantly associated with larger <i>TP53</i> clone size, bi-allelic status, and the absence of concurrent mutations, reflecting the high <i>TP53</i> mutational burden. Specifically, 51 patients (81%) with the dominant <i>TP53</i> clone greatly overlapped with those with the complex karyotype. Multivariable overall survival (OS) analysis identified AML (hazard ratio [HR], 2.51; <i>P</i> = 0.03) and <i>TP53</i> clonal dominance (HR, 5.30; <i>P</i> = 0.002) as prognostic factors. One-year OS was worse in AML with the dominant <i>TP53</i> clone than in others (13% vs 61%; <i>P</i> &lt; 0.001). Our results underscore the utility of mutational profile-guided risk stratification in patients with <i>TP53</i>-mutant AML/MDS, and could aid in transplantation-related decision-making.</p>

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Transplantation outcomes of TP53-mutant AML and MDS: a single transplantation center experience of 63 patients

  • 期刊论文

  • 发表日期：

    2025年2月26日

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  • Yasutaka Masuda,
  • Daichi Sadato,
  • Takashi Toya,
  • Yuzuru Hosoda,
  • Chizuko Hirama,
  • Hiroaki Shimizu,
  • Yuho Najima,
  • Hironori Harada,
  • Yuka Harada,
  • Noriko Doki

摘要

Allogeneic hematopoietic stem cell transplantation is recommended for TP53-mutant acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) despite a high relapse rate and poor survival. To understand TP53 alterations on a molecular level and define stratified prognostic outcomes following transplantation, we performed targeted next-generation sequencing on 63 patients who underwent transplantation for TP53-mutant AML/MDS and profiled their molecular spectrum. Sixty-eight TP53 mutations were detected, with a median variant allele frequency of 46.8%. Copy number alterations at the TP53 locus were present in 19 patients (30%). Complex karyotype was detected in 48 patients (76%) and was significantly associated with larger TP53 clone size, bi-allelic status, and the absence of concurrent mutations, reflecting the high TP53 mutational burden. Specifically, 51 patients (81%) with the dominant TP53 clone greatly overlapped with those with the complex karyotype. Multivariable overall survival (OS) analysis identified AML (hazard ratio [HR], 2.51; P = 0.03) and TP53 clonal dominance (HR, 5.30; P = 0.002) as prognostic factors. One-year OS was worse in AML with the dominant TP53 clone than in others (13% vs 61%; P < 0.001). Our results underscore the utility of mutational profile-guided risk stratification in patients with TP53-mutant AML/MDS, and could aid in transplantation-related decision-making.