Impact of germline predisposition genes to hematologic malignancies on transplant outcomes and donor selection

Introduction Germline predisposition gene mutations may influence outcomes in patients undergoing hematopoietic stem cell transplantation (HSCT). Methods This retrospective study of 558 patients undergoing HSCT (allo-HSCT in 557 cases, auto-HSCT in 1 case) evaluated the impact of germline predisposition gene mutations on outcomes. Results Enrichment of HAVCR2 mutations in B-NHL and UNC13D mutations in MDS was associated with poorer prognosis. While homozygous mutation carriers (7.5%) overall did not have reduced survival, their outcomes were significantly better with unrelated versus related donors (3-year DFS/OS: 82.1% vs. 48.3%/56.7%). Mutations in genes linked to inborn errors of immunity affecting both cellular and humoral immunity (IACHI) predicted inferior survival. Conclusion Germline mutations, particularly in IACHI-related genes, influence HSCT outcomes. Pre-transplant genetic screening and opting for unrelated donors for homozygous carriers may optimize transplantation strategies.