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 was 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 were 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.