Characterisation of TP53 mutational features and outcomes of acute myeloid leukaemia after allogeneic haematopoietic cell transplantation

TP53 mutations define a clinically distinct subset of acute myeloid leukaemia (AML) associated with complex cytogenetics and therapy resistance. We performed a retrospective single-centre analysis of 61 consecutive TP53-altered AML patients undergoing first allogeneic haematopoietic cell transplantation (allo-HCT) at the Medical Center Freiburg (2007-2025), compared with 636 TP53-wild-type controls. TP53-altered patients had markedly inferior overall survival (median 379 vs. 1694 days; 5-year OS 18% vs. 50%; p < 0.001). Excess relapse was the primary driver (5-year cumulative incidence 55% vs. 33%; p < 0.001), whereas non-relapse mortality did not differ (28.5% vs. 23%; p = 0.426). On multivariable Cox analysis, TP53 alteration was the strongest independent predictor of inferior OS (HR 2.54, 95% CI 1.77-3.64; p < 0.001), and this association persisted after adjustment for cytogenetic risk and for the refined Disease Risk Index. In an exploratory hierarchical clustering analysis extended by seven patients from a second centre, two subgroups emerged: a del(17p)-enriched cluster (n = 12; median OS 5.7 months) and a TP53 point mutation-enriched cluster (n = 56; median OS 15.1 months). TP53-altered AML is confirmed as the strongest independent adverse prognostic factor after allo-HCT, and molecular heterogeneity within this subtype may inform trial stratification and targeted post-transplant interventions.