SYSTEMATIC REVIEW article
Front. Transplant.
Sec. Vascularized Composite Allotransplantation
Immunosuppressive and Antiinfectious Regimens in Vascular Composite Allograft Recipients – A Systematic Review
Provisionally accepted
Leonard Knoedler1
Tobias Niederegger2Thomas Schaschinger2
Gabriel Hundeshagen2,3
Javier Gonzalez4,5*
Samuel A. Knoedler6
Martin Kauke-Navarro MD6
Jasper Iske1Curtis L. Cetrulo5Maxime Jeljeli5
Elena Hofmann1
Max Heiland1
Steffen Koerdt1
Alexandre G. Lellouch5,7,8- 1Charite - Universitatsmedizin Berlin, Berlin, Germany
- 2Universitat Heidelberg, Heidelberg, Germany
- 3BG Klinik Ludwigshafen, Ludwigshafen, Germany
- 4University of Arizona, Tucson, United States
- 5Cedars-Sinai Medical Center, Los Angeles, United States
- 6Yale University School of Medicine, New Haven, United States
- 7Massachusetts General Hospital, Boston, United States
- 8Shriners Children's Boston, Boston, United States
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ABSTRACT Introduction: 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. Methods: 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. Results: 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.
Keywords: Vascularized Composite Allotransplantation, Immunosuppression, Tacrolimus, Mycophenolate mofetil, antithymocyte globulin, Infection prophylaxis, Graft Survival, Systematic review
Received: 28 Sep 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Knoedler, Niederegger, Schaschinger, Hundeshagen, Gonzalez, Knoedler, Kauke-Navarro MD, Iske, Cetrulo, Jeljeli, Hofmann, Heiland, Koerdt and Lellouch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Javier Gonzalez
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