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

Abstract

he advent of vascularized composite allotransplantation (VCA) provides a comprehensive reconstructive option for patients with extensive injuries. Since the first hand transplant in 1998 and first face transplant (FT) in 2005, medical technology, preoperative evaluation, operative technique, and posttransplant care have evolved considerably. For instance, the advent of calcineurin inhibitors, computerized surgical planning (CSP), and the inclusion of vascularized bone in FT have all played an important role in Background: Of nearly 90 hand and 50 face transplant recipients, only five have received a cross-sex vascularized composite allotransplantation (CS-VCA). CS-VCA has the potential to expand the donor pool and has been proven anatomically feasible and ethically acceptable in previous studies. However, there is a lack of immunologic data. This study evaluated the immunologic feasibility of CS-VCA through analysis of the solid organ transplant literature, given the paucity of CS-VCA data. The authors hypothesize that rates of acute rejection (AR) and graft survival (GS) in CS versus same-sex (SS) solid organ transplantation are similar. Methods: A systematic review and meta-analysis were performed. 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), femaleto-male, and overall]. Results: A total of 693 articles were initially identified with 25 included in the meta-analysis. No significant difference in GS was noted between SS-KT versus CS-KT [OR, 1.04 (95% CI, 1.00 to 1.07); P = 0.07), SS-KT versus MTF-KT [OR, 0.97 (95% CI, 0.90 to 1.04); P = 0.41), and SS-LT versus MTF-LT [OR, 0.95 (95% CI, 0.91 to 1.00); P = 0.05). No significant difference in AR was noted between SS-KT versus MTF-KT [OR, 0.99 (95% CI, 0.96 to 1.02); P = 0.57), SS-LT versus CS-LT [OR, 0.78 (95% CI, 0.53 to 1.16); P = 0.22], or SS-LT versus female-to-male LT [OR, 1.03 (95% CI, 0.95 to 1.12); P = 0.47]. For the remaining pairings, GS was significantly increased and AR was significantly decreased in the SS transplants. Conclusions: Published data suggest immunologic feasibility of CS-KT and CS-LT with the potential for generalization to the VCA population. (Plast. Reconstr. Surg. 153: 839, 2024.) Clinical Relevance Statement: In theory, CS-VCA could expand the potential donor pool, ultimately leading to decreased wait times for recipients and improve the likelihood of establishing a immunologically favorable donorrecipient match.