Bridging TP53-mutated myelodysplastic syndrome/acute myeloid leukemia to transplant: is venetoclax part of the answer?

PURPOSE OF REVIEW: TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remain among the most challenging myeloid malignancies, with poor long-term outcomes despite allogeneic stem cell transplantation (HCT). Venetoclax-based regimens produce encouraging response rates, but their role as optimal pre-transplant therapy for TP53 mutated MDS/AML remains unconfirmed. This review evaluates the rationale and clinical evidence supporting venetoclax as a bridging strategy to HCT. RECENT FINDINGS: Recent studies have refined risk stratification through TP53 allelic-state characterization, demonstrating poor transplant outcomes. Studies show venetoclax-based therapy may induce deeper and faster remissions. A higher proportion of patients who receive venetoclax successfully transition to transplantation. However, higher response rates do not consistently translate into a survival advantage post-transplant. Efforts to study venetoclax regimens in the pre-transplant setting lack stratification by TP53 allelic state or design focus for this subgroup. SUMMARY: Current evidence supports venetoclax as an acceptable bridging strategy to accelerate response and cytoreduction for TP53-mutated MDS/AML. There is a limited number of studies of venetoclax-containing regimens specific for transplant eligible patients with TP53 mutated MDS/AML. It is important for future studies to incorporate a standardized TP53 allelic-state assessment, molecular measurable residual disease evaluation, and transplant-specific endpoints.