Peri-transplant TP53 molecular MRD as a prognostic biomarker of relapse in TP53-mutated AML/MDS undergoing allogeneic HCT

TP53 mutations occur in up to 20% of patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) and define a distinct high-risk disease subtype [ 1 ]. Allogeneic hematopoietic stem-cell transplant (allo-HCT) remains the only potential curative approach, however, outcomes remain poor because of high relapse rates driven by persistent measurable residual disease (MRD) despite transplantation [ 2 , 3 ]. The detection of genetic MRD is a well-established predictive factor for specific AML subtypes, including those with NPM1 , CBF alterations, and MLL rearrangements [ 4 ]. However, no standardized method currently exists for MRD testing for TP53 -mutated disease. Moreover, the prognostic significance of pre- and post-transplant molecular MRD for predicting relapse after HCT in this high-risk population remains controversial. Previous studies using deep sequencing reported limited predictive utility. Grob et al. [ 5 ] found no association between TP53 MRD and outcomes in patients achieving complete remission, outside transplant-specific cohorts, while Sallman et al. [ 6 ] showed post-transplant MRD by duplex sequencing did not predict survival in a small cohort receiving APR-246 maintenance. Given this ongoing uncertainty, more definitive evaluation is needed. Droplet digital PCR (ddPCR) provides rapid and highly sensitive quantification (down to 0.001%) [ 7 ], and our prior work demonstrated that early post-transplant ddPCR can effectively stratify relapse risk in AML and MDS [ 8 ]. Therefore, we conducted a multicenter cohort study to assess peri-HCT molecular MRD in TP53 -mutated patients using a ddPCR-based platform. Detailed study design and statistical methods are provided in the Supplemental Materials.