Transplant Cell Ther. 2026 Apr 11. pii: S2666-6367(26)00257-5. [Epub ahead of print]
Moataz Ellithi,
Sandeep Raj,
Maria Bromberg,
Ilan Goldstein,
Amethyst Saldia,
Esperanza B Papadopoulos,
Boglarka Gyurkocza,
Doris M Ponce,
Brian C Shaffer,
Roni Tamari,
James W Young,
Ioannis Politikos,
Gunjan L Shah,
Mohammad Alhomoud,
Gagan Raju,
Charlotte F M Hughes,
Parastoo B Dahi,
Michael Scordo,
Sergio A Giralt,
Miguel-Angel Perales,
Aaron D Goldberg,
Ellin Berman,
Xin Wang,
Eytan M Stein,
Mithat Gonen,
Ann A Jakubowski,
Richard J Lin.
BACKGROUND: Myeloid malignancies with TP53 alterations are characterized by genomic instability, chemotherapy resistance, and very poor outcomes even after allogeneic hematopoietic cell transplantation (allo-HCT). Hypomethylating agents (HMAs), small molecule targeted therapies, and donor lymphocyte infusion (DLI) are often used post-transplant to mitigate relapse risk in high-risk myeloid malignancies, but their impact on survival in TP53-mutated disease remains uncertain.
OBJECTIVES: To evaluate the impact of post-transplant interventions and graft-versus-host disease (GVHD) on relapse and survival outcomes in patients with TP53-mutated or chromosomal 17p-deleted myeloid malignancies.
STUDY DESIGN: This is a single-center retrospective study of adult patients with TP53-mutated and/or chromosomal 17p-deleted myeloid malignancies who underwent first allo-HCT between 2014 and 2023. Survival outcomes were assessed using the Kaplan-Meier method. Univariable Cox proportional hazards regression was used to assess associations of baseline characteristics with outcomes. Analyses of post-HCT interventions (maintenance/preemptive HMAs, targeted therapies, and/or DLI) and the development of chronic GVHD (classic chronic or acute/chronic overlap) were landmarked at 60 and 180 days, respectively, and both exposures were treated as time-dependent covariates. Cause-specific multivariable Cox proportional hazards regression models adjusted for baseline covariates were fitted to assess associations of outcomes with the time-dependent exposures. Pre-specified subgroup analyses were performed for the ultra-high-risk group, defined as complex karyotype and/or ≥2 TP53/17p alterations.
RESULTS: Among 158 patients (median age 65 years, IQR: 57- 70), acute myeloid leukemia (54%) and myelodysplastic syndromes (40%) were the most common myeloid malignancies. Complex karyotypes were present in 68%, and ultra-high-risk features were present in 73%. Reduced-intensity conditioning was used in 59%. Approximately 49% of patients received post-HCT interventions; 68% of these were administered before relapse (preemptively or as prophylaxis/maintenance). In a landmark analysis at day 60 post-HCT (N=145), pre-relapse HMA, targeted therapies, and/or DLI was not associated with improved overall survival (OS) (HR 0.95; 95% CI: 0.56, 1.62; p=0.80), progression free survival (PFS) (HR 0.95; 95% CI: 0.49, 1.30; p=0.40), or cumulative incidence of relapse (CIR) (HR 1.05; 95% CI: 0.60, 1.85; p=0.90) after adjusting for key baseline characteristics. Similarly, in a landmark analysis at day 180 post-HCT (N=100), the occurrence of chronic GVHD was not associated with OS (HR 0.78; 95% CI: 0.24, 2.61; p=0.70), PFS (HR 0.67; 95% CI: 0.20, 2.23; p=0.50), or CIR (HR 0.34; 95% CI: 0.05, 2.54; p=0.30). Findings were similar in the ultra-high-risk subgroup (N=115) where post-HCT interventions showed no association with OS (HR 0.81; 95% CI: 0.45, 1.45; p=0.50), PFS (HR 0.72; 95% CI: 0.42, 1.24; p=0.20), or CIR (HR 0.87; 95% CI: 0.46, 1.62; p=0.70).
CONCLUSIONS: In this single center study, preemptive or prophylactic post-HCT interventions did not significantly improve survival or reduce relapse risk in patients with TP53-altered myeloid malignancies, including those with ultra-high-risk features. While the study was limited by its small sample size and heterogeneous interventions, these findings highlight the urgent need to develop novel therapeutic strategies for this high-risk population.
Keywords: Chronic graft-versus-host disease; Donor lymphocyte infusion; Post-transplant maintenance therapy; Relapse prevention; TP53 mutant myeloid neoplasms