Preemptive hematopoietic stem cell transplantation in RUNX1 familial platelet disorder: a shared decision-making framework

Abstract

RUNX1 familial platelet disorder (RUNX1-FPD) is associated with a 35% to 50% lifetime risk of hematologic malignancy (HM), and like all germline HM predisposition syndromes, can only be cured with allogeneic hematopoietic stem cell transplantation (HSCT). Current genetic screening techniques allow for early detection of germline predisposition, and consequently, the opportunity for HSCT before overt development of HM (ie, preemptive HSCT). However, there is not yet a consensus on the use of preemptive HSCT for RUNX1-FPD. Described here is the case of an individual with RUNX1-FPD and a family history of HM who underwent preemptive HSCT. We introduce a shared decision-making framework designed to support individuals with RUNX1-FPD, their families, and their multidisciplinary clinical teams in evaluating whether and when to pursue preemptive HSCT versus continued surveillance. The framework reviews key medical factors that influence HSCT timing decisions, including germline and somatic variants, clonal changes over time, familial history of HM, early morphologic or hematologic features, bleeding-related quality of life impacts, and donor availability. The framework also summarizes the major risks and uncertainties potentially associated with preemptive HSCT while highlighting the associated ethical challenges. Together, the case and framework provide a structured, patient-centered approach for navigating the complex clinical decision of preemptive HSCT. Ongoing collaborative efforts to define cytogenetic and clonal changes preceding malignant transformation in RUNX1-FPD will refine the framework and bolster individualized treatment strategies aimed at preventing HM and improving the quality of life of individuals with RUNX1-FPD.