The Impact of Post-Transplant Interventions and Chronic GVHD on Survival in Myeloid Malignancies Harboring TP53 Alterations

A recent single-center retrospective study, published in Transplantation and Cellular Therapy, investigated post-transplant outcomes in patients with TP53-mutated or 17p-deleted myeloid malignancies treated with allogeneic hematopoietic cell transplantation (allo-HCT). This study, performed by researchers from Memorial Sloan Kettering Cancer Center, demonstrated that pre-emptive or prophylactic post-transplant interventions, including hypomethylating agents (HMAs), targeted therapies, and donor lymphocyte infusion (DLI), are not associated with improved survival or reduced relapse. Further, the development of chronic graft-versus-host disease (cGVHD) was also not associated with improved survival or reduced relapse. Therefore, conventional post-transplant strategies appear inadequate for this high-risk population, underscoring an urgent unmet need for novel therapeutic approaches.

TP53-altered myeloid malignancies, present in 10–20% of AML/MDS cases, are defined by chemoresistance, genomic instability, and median post-transplant survival under 12 months. Despite allo-HCT remaining the only potentially curative option, relapse rates are high in these patients, and long-term survival is estimated to be low at 20–30%. The authors therefore investigated adult patients with myeloid malignancies harboring TP53 alterations who underwent first allo-HCT between January 2014 and December 2023. Analyses were performed at day 60 for post-transplant interventions and day 180 for cGVHD.

Among the 158 patients (median age 65 years; AML 54%, MDS 40%), 68% had complex karyotype and 73% fulfilled ultra-high-risk criteria. Median OS was 17 months (95% CI: 14–26) and median PFS was 9.2 months (95% CI: 6.8–14). Two-year OS and PFS were 43% and 34%, respectively, with a cumulative incidence of relapse of 46% at 2 years. Day 60 landmark analysis (n=145), prerelapse interventions showed no association with OS, PFS, or CIR. At day 180 (n=100), cGVHD was similarly not associated with OS, PFS, or CIR. These findings were consistent in the ultra-high-risk subgroup (n=115), with median OS of only 14 months. Overall, this study provides critical real-world evidence that current post-transplant strategies offer no measurable survival benefit in TP53-altered myeloid disease, highlighting the need for novel approaches such as p53 reactivators, CD123-targeted therapies, and MRD-guided immune profiling strategies.

Reference:

Ellithi M, Raj S, Bromberg M, et al. The Impact of Post-Transplant Interventions and Chronic GVHD on Survival in Myeloid Malignancies Harboring TP53 Alterations. Transplant Cell Ther. Published online April 12, 2026. http:doi.org/10.1016/j.jtct.2026.03.039