Graft Survival and Acute Rejection in Cross-Sex Solid Organ Transplants: A Systematic Review and Meta-Analysis to Inform Vascularized Composite Allotransplantation Practice

Out of nearly 90 hand and 50 face transplant recipients, only 5 have received a cross-sex vascularized composite allotransplantation (CS-VCA) to date. CS-VCA has the potential to expand the donor pool and has been shown to be anatomically feasible and ethically acceptable in previous cadaveric and survey studies. However, there is a lack of immunologic data. This study aims to evaluate the immunologic feasibility of CS-VCA through analysis of the solid organ transplant (SOT) literature, given the paucity of CS-VCA data. We hypothesize the rates of acute rejection (AR) and graft survival (GS) in CS vs. same-sex (SS)-SOT to be similar.A systematic review and meta-analysis of the PubMed, EMBASE, and Cochrane databases were performed in accordance with PRISMA guidelines. Studies comparing GS or AR episodes in CS- and SS- adult kidney (KT) and liver transplant (LT) populations were included. Odds ratios were calculated for overall GS and AR for all SS and CS transplant combinations (male-to-female (MTF), female-to-male (FTM) and overall).A total of 693 articles were initially identified and 25 studies were included in the meta-analysis. No significant difference in GS was noted between SS-KT vs. CS-KT (OR 1.04 [1.00, 1.07]; P=0.07), SS-KT vs. MTF-KT (OR 0.97 [0.90, 1.04]; P=0.41) and SS-LT vs. MTF-LT (OR 0.95 [0.91, 1.00]; P=0.05). No significant difference in AR was noted between SS-KT vs. MTF-KT (OR 0.99 [0.96, 1.02]; P=0.57), SS-LT vs. CS-LT (OR 0.78 [0.53, 1.16]; P=0.22) and SS-LT vs. FTM-LT (OR 1.03 [0.95, 1.12]; P=0.47). For the remaining pairings, GS was significantly increased and AR was significantly decreased in the SS transplants.Published data suggest immunologic feasibility of CS-KT and CS-LT, with the potential for generalization to the VCA population. In theory, CS-VCA could expand the potential donor pool, leading to decreased wait times for recipients.