Impact of germline predisposition genes to hematologic malignancies on transplant outcomes and donor selection.
In a retrospective cohort of 558 HSCT recipients, germline predisposition variants—particularly homozygous variants and variants in genes affecting cellular and humoral immunity—were associated with transplant outcomes, including better survival among homozygous carriers receiving unrelated rather than related donor grafts.
Open original publication →What the AI sees
In a retrospective cohort of 558 HSCT recipients, germline predisposition variants—particularly homozygous variants and variants in genes affecting cellular and humoral immunity—were associated with transplant outcomes, including better survival among homozygous carriers receiving unrelated rather than related donor grafts.
Research significance
The reported associations support the hypothesis that pre-transplant germline testing could help stratify HSCT risk and inform donor selection, especially by avoiding potentially variant-sharing related donors for homozygous carriers; however, this is an inference from retrospective data and does not establish a donor-selection standard.
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.