Genetic Factors and the Outcomes of Transplant-Associated Thrombotic Microangiopathies

Transplant-associated thrombotic microangiopathy (TA–TMA) is a severe endothelial complication following allogeneic hematopoietic stem-cell transplantation (allo-HSCT), associated with high mortality when not promptly diagnosed and treated. This study aimed to delineate the genetic landscape associated with TA–TMA and assess its impact on clinical outcomes. We retrospectively analyzed 1069 allo-HSCT recipients between January 2016 and May 2020, identifying 131 patients who met diagnostic criteria for TA–TMA (incidence rate: 12.25%). Genomic DNA sequencing was performed targeting 17 complement- related genes, identifying 74 genetic variants in 58 TA–TMA patients, including seven large deletions within the CFH–CFHR5 locus. Survival analysis indicated significantly poorer outcomes for TA–TMA patients compared to non-TMA patients (24.4% vs 62.4% survival at maximum follow-up, p = 0.025). However, cumulative incidence curves revealed no significant difference in TA–TMA onset between genetic variant carriers and non-carriers. These findings underscore the complexity of TA–TMA pathogenesis, suggesting that genetic predisposition alone is insufficient without additional endothelial insults. The limited predictive value of individual markers highlights the need for integrated biomarker strategies. Future research should focus on refining risk stratification models incorporating comprehensive genetic profiles, dynamic biomarkers, and longitudinal clinical parameters to enable earlier identification and targeted interventions, thereby improving post-transplant survival outcomes.