Impact of germline predisposition genes to hematologic malignancies on transplant outcomes and donor selection.
In a retrospective cohort of 558 predominantly allogeneic HSCT recipients, germline predisposition variants—including IACHI-related mutations—were associated with transplant outcomes, and homozygous carriers had better reported outcomes with unrelated rather than related donors.
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In a retrospective cohort of 558 predominantly allogeneic HSCT recipients, germline predisposition variants—including IACHI-related mutations—were associated with transplant outcomes, and homozygous carriers had better reported outcomes with unrelated rather than related donors.
Research significance
The study provides associative evidence that pre-transplant germline screening could inform donor selection; it supports, but does not establish, the hypothesis that avoiding potentially variant-sharing related donors may improve outcomes for homozygous mutation carriers.
Source abstract
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.