# The prognostic impact of myeloid co-mutation burden in TP53-mutated AML/MDS after allogeneic stem cell transplantation: a multicenter retrospective analysis

## TL;DR

This study finds that TP53-mutated AML/MDS patients with fewer myeloid co-mutations after stem cell transplants have worse survival outcomes, suggesting a new way to assess risk.

## Contribution

The study introduces myeloid co-mutation burden as a novel prognostic factor for TP53-mutated AML/MDS patients post-transplant.

## Key findings

- Low myeloid co-mutation burden (<2) is linked to significantly worse overall and progression-free survival in TP53-mutated AML/MDS patients after allo-HSCT.
- A composite model combining co-mutation burden and karyotype improves risk stratification for these patients.
- Outcomes did not differ between AML and MDS patients in this cohort.

## Abstract

TP53 mutations are associated with poor prognosis in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a potential cure, but outcomes are suboptimal and risk stratification remains challenging. This multi-center, retrospective study analyzed 66 patients with TP53-mutated AML/MDS who underwent allo-HSCT. The study endpoints included overall survival (OS), progression-free survival (PFS), and cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and Graft-versus-host disease-free, relapse-free survival (GRFS). After median 1054-day follow-up, 3-year rates for OS, PFS, CIR, NRM, and GRFS were 47.2%, 39.7%, 37.3%, 23%, and 37.4%, respectively. Survival did not differ between AML and MDS. Univariate analysis showed that < 2 somatic myeloid co-mutations predicted inferior OS (3-y OS: 32% vs. 65.9%, p = 0.02) and PFS (27.6% vs. 59.1%, p = 0.01). Age > 50 years adversely affected PFS, and complex karyotype showed a negative trend. Multivariate analysis found no independent factors, likely due to sample size and collinearity. A combined risk factor analysis revealed that patients with ≥ 1 adverse factor (either co-mutations < 2 or complex karyotype) had significantly worse OS (3-y OS: 72.6% vs. 37.2%, p = 0.04) and PFS (3-y PFS: 67.7% vs. 28.9%, p = 0.02) compared to those with neither risk factor. In patients with TP53-mutated AML/MDS undergoing allo-HSCT, a low myeloid co-mutation burden (< 2) is strongly associated with poor outcomes. A composite model integrating co-mutation burden with karyotype may assist in post-transplant risk stratification, offering a practical supplementary parameter when TP53 allelic status is uncertain. This finding requires validation in larger prospective studies.

The online version contains supplementary material available at 10.1007/s00277-026-06895-4.