Immunosuppressive and antiinfectious regimens in vascular composite allograft recipients-a systematic review

Vascularized composite allotransplantation (VCA) has achieved significant clinical success, but lifelong immunosuppression remains essential to prevent rejection. Despite potent regimens, including tacrolimus, mycophenolate mofetil, and steroids, rejection episodes frequently occur within the first postoperative year. The side effects of immunosuppressive drugs must be carefully balanced against the risks of insufficient therapy. This review specifically aims to evaluate current immunosuppressive regimens and infection prophylaxis in VCA to identify evidence based approaches that attempt to mitigate rejection, prevent infections, and improve long-term graft survival.

A systematic review was conducted across PubMed/MEDLINE, EMBASE, and Web of Science databases, adhering to PRISMA 2020 guidelines. Inclusion criteria focused on studies reporting immunosuppressive regimens, dosages, and infection prophylaxis in VCA surgery. Non-VCA, animal, feasibility studies, and non-English publications were excluded.

Of 1,150 screened articles, 42 met inclusion criteria. Upper extremity and facial VCAs represented 50% and 29% of cases, respectively, with traumatic amputation as the primary indication (37%). Antithymocyte globulin was the most common induction drug, while tacrolimus, mycophenolate mofetil, and steroids were predominant for maintenance therapy in 33% and 11% of cases, respectively. Infection prophylaxis was used in 31% of cases. Drug dosages varied widely, and no standardized immunosuppressive protocols were identified.

Current immunosuppressive strategies in VCA lack standardization, leading to variability in outcomes and increased risks. Infection prophylaxis remains underutilized despite recipient vulnerability. There is a critical need for standardized and tailored guidelines to optimize immunosuppressive therapy and infection control, ensuring graft survival and improved patient outcomes.