Evaluating the efficacy of umbilical cord blood transplantation in TP53-mutated AML/MDS: Encouraging survival outcomes

Abstract Introduction Subtype of MDS/AML carrying TP53 mutations is reported to have poor outcomes , and it often does not respond to currently treatments. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is considered the only potential curative treatment for these type of myeloid malignancies. Although it is often recommended for eligible patients with TP53 mutations to undergo HSCT, there are limited data regarding the efficacy and outcomes of umbilical cord blood transplantation (UCBT) in TP53-mutated patients. Methods The purpose of this study was to depict clinical overview of TP53 aberrations and its impact on survival in patients with MDS/AML undergoing UCBT. We identified 23 unique patients with AML (20 [86.9%]) and MDS (3 [13.0%]) harboring a known pathogenic TP53 mutation treated at The First Affiliated Hospital of USTC between January 2015 to June 2024. All the surviving patients were followed up until 2025/7/1 . The median follow-up of the whole cohort was 22.9 months .For the patients' data, Kaplan-Meier analysis with log-rank test was used to estimate leukemia-free survival (LFS) and overall survival (OS) from the time of UCBT. Graft-versus-host disease-free relapse-free survival (GRFS),cumulative incidences of relapse (CIR), graft-versus-host disease (GVHD)and non-relapse mortality (NRM) were performed as defined by the Fine and Gray model. Results We identified 23 patients (12 males/11 females) with TP53 mutation prior to UCBT with AML and MDS. The 3-year OS for the entire cohort was 42.2% (95% CI: 21.8–61.3%). Among AML/MDS patients with TP53 mutations, a relatively high 3-year LFS (42.7% [95% CI: 22.4–61.6%]) and GRFS (38.3% [95% CI: 18.9–57.4%]) were achieved after receiving UCBT. Meanwhile, a relatively low 3-year CIR (22.52% [95% CI: 8.2–41.2%]) and NRM (34.78% [95% CI: 16.6–53.7%]) were also observed. Additionally, for the entire cohort, the 42-day neutrophil engraftment rate was 95.65% [95% CI: 81.757–99.7%], the 60-day platelet engraftment rate was 69.57% [95% CI: 50.72–86.5%], the cumulative incidence of grade II-IV acute GVHD was 34.78% [95% CI: 19.155–57.7%], and the cumulative incidence of grade III-IV acute GVHD was 13.04% [95% CI: 4.404–35.2%]. Conclusions These results indicate that despite the universally poor prognosis associated with TP53 mutations, UCBT can achieve substantial survival rates. Compared to the approximate 10-20% 3-year OS reported in other studies for TP53-mutated AML/MDS patients post-transplantation, the observed 3-year OS of 42.2% (n=23) in this cohort represents an improvement. Although this study had a relatively limited sample size (n=23), provide new insights into UCBT application for TP53-mutated AML/MDS patients. This finding suggests that with stringent patient selection criteria, UCBT may offer an effective therapeutic option for this high-risk population, potentially surpassing outcomes achievable with some conventional transplantation approaches.