Impact of TP53 variants and germline mutations on allogeneic stem cell transplantation outcomes in acute myeloid leukemia and myelodysplastic neoplasms

Abstract

TP53-mutated myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) are typically characterized by complex cytogenetic abnormalities and resistance to intensive chemotherapy [1, 2]. Allogeneic stem cell transplantation (allo-HSCT) remains the only curative option, yet the outcomes of germline versus somatic TP53-mutated AML/MDS under allo-HSCT remain poorly explored. Moreover, the prognostic impact of TP53 mutations (TP53mut) across different domains is not well characterized. Additionally, the effects of missense versus truncating mutations [3, 4] and the prognostic significance of multi-hit TP53 status in AML/MDS remain controversial [5, 6]. Given the clinical and biological heterogeneity of TP53 mutations, this multi-center retrospective study aims to delineate the differences between germline and somatic TP53mut to refine disease trajectories and optimize transplant strategies.

Somatic mutations were identified by next-generation sequencing, while germline TP53 variants were confirmed using oral mucosa testing. Germline TP53mut carriers received allo-HSCT from related donors negative for the corresponding variant. Pre-transplant MRD was assessed by multiparameter flow cytometry (MFC) on bone marrow, with MRD positivity defined as ≥0.01% leukemic-associated immunophenotypes.