Evaluating allogeneic transplant for TP53 mutated acute myeloid leukemia

OncotargetOct 12 2024

A new editorial was published in Oncotarget's Volume 15 on October 1, 2024, entitled, "Transplant or no transplant for TP53 mutated AML."

As highlighted in this editorial, TP53 mutations (mut) occur in 10–15% of acute myeloid leukemia (AML) cases, commonly associated with therapy-related AML (t-AML) and complex cytogenetics (CG). TP53-mut AML is inherently resistant to conventional chemotherapies and continues to show a poor prognosis, even with venetoclax-based therapies. Allogeneic hematopoietic stem cell transplant (allo-HCT) remains a potential curative option, though only 10–15% of patients receive it. In a recent study, allo-HCT was the only variable significantly improving survival, despite only 16% of patients successfully bridging to it.

In their editorial, researchers Talha Badar, Moazzam Shahzad, Ehab Atallah, Mark R. Litzow, and Mohamed A. Kharfan-Dabaja from the Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program at Mayo Clinic (Jacksonville, Florida) evaluated the outcomes of TP53-mutated AML patients based on data from the Consortium of Myeloid Malignancies and Neoplastic Diseases (COMMAND). The study found a "dismal" survival rate of 8.5 months, with no significant difference among treatment types, and allo-HCT was the only variable associated with improved survival.

The authors also report on the "better long-term outcomes" when allo-HCT was performed during Complete Remission 1 (CR1) in previous observations. They acknowledge the limitations of their retrospective analysis, including selection bias, data heterogeneity from participating institutions, and the lack of complete molecular data prior to allo-HCT that might have influenced the results. Nevertheless, the findings are encouraging and suggest that allo-HCT improves long-term outcomes in this poor prognostic disease, where effective therapies remain limited.

"In summary, this study reported improved survival when allo-HTC was performed in CR1 versus after later lines of therapy."