Utility or futility? A contemporary approach to allogeneic hematopoietic cell transplantation for TP53-mutated MDS/AML

Abstract

Abstract TP 53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are among the most lethal malignancies, characterized by dismal outcomes with currently available therapies. Allogeneic hematopoietic cell transplantation (allo-HCT) is widely thought to be the only treatment option to offer durable disease control. However, outcomes with allo-HCT in this context are quite poor, calling into question the utility of transplantation. In this review, we summarize the latest data on allo-HCT outcomes in this subgroup, evaluating the limitations of available evidence; we review the molecular heterogeneity of this disease, delineating outcomes based on distinct biological features to aid in patient selection; and we critically examine whether allo-HCT should be routinely applied in this disease on the basis of currently available data. We propose that the exceptionally poor outcomes of patients with TP53-mutated MDS/AML with biallelic loss and/or adverse-risk cytogenetics should motivate randomized-controlled trials of HCT vs non-HCT to determine whether transplantation can prolong survival and/or positively impact other clinically relevant outcomes such as patient-reported outcomes or healthcare resource utilization in this disease subset. Without dedicated prospective randomized trials, selecting who may actually derive benefit from allo-HCT for TP53-mutated MDS/AML can be described as ambiguous guesswork and must be carefully contemplated.