Genetic Polymorphisms of Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and clinical outcomes post allogeneic hematopoietic stem cell transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE Although HLA-matching is considered as a key genetic predictor of allo-HSCT outcomes, genetic polymorphisms in non-HLA genes, especially in genes encoding immunoregulatory proteins, have also been proposed as additional risk factors linked to the occurrence of transplant complications. This study aimed to carry out a systematic review and meta-analysis from all eligible cohort studies to determine the effect of CTLA-4 gene polymorphisms, including rs231775, rs3087243, rs4553808, rs5742909, and rs733618, on clinical outcomes in patients receiving an allo-HSCT. METHODS A systematic literature search in PubMed, Web of Science, and Scopus were performed to identify the relevant studies, and related information was extracted. The effect size (ES) and corresponding 95% confidence intervals (CIs) were calculated to estimate the association. RESULTS 16 studies were eligible and included in the meta-analysis. The pooled results showed that only the dominant models of rs3087243 was significantly associated with chronic GVHD (cGVHD), while other SNPs were not significantly associated with Overall Survival, Disease-Free Survival, Relapse, and GVHD. CONCLUSIONS Our study represents, for the first time, a comprehensive meta-analysis on the role of CTLA-4 polymorphisms on outcomes after allo-HSCT. The results indicate that the CT60 CTLA-4 polymorphism could be a significant risk factor for cGVHD.