Defining chronic rejection in vascularized composite allotransplantation-The American Society of Reconstructive Transplantation and International Society of Vascularized Composite Allotransplantation chronic rejection working group: 2018 American Society of Reconstructive Transplantation meeting report and white paper Research goals in defining chronic rejection in vascularized composite allotransplantation.
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2020-01
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This report summarizes a collaborative effort between the American Society of Reconstructive Transplantation and the International Society of Vascularized Composite Allotransplantation to establish what is known about chronic rejection in recipients of vascularized composite allografts, with an emphasis on upper extremity and face transplants. As a picture of chronic rejection in hand and face vascularized composite allografts emerges, the results will be applied to other types of vascularized composite allografts, such as uterine transplantation.Methods
The overall goal is to develop a definition of chronic rejection in vascularized composite allografts so that we can establish longitudinal correlates of factors such as acute rejection, immunosuppressive therapy, de novo donor-specific antibody and trauma/infection and other external factors on the development of chronic rejection. As Dr Kanitakis eloquently stated at the 2017 International Society of Vascularized Composite Allotransplantation meeting in Salzburg, "Before we can correlate causative factors of chronic rejection, we have to define what chronic rejection in VCA is."Results
The first meeting report was presented at the sixth Biennial meeting of the American Society of Reconstructive Transplantation in November 2018. Based on collaborative efforts and descriptions of clinical cases of chronic rejection in vascularized composite allograft recipients, a working definition of chronic rejection in vascularized composite allografts with respect to overt functional decline, subclinical functional decline, histologic evidence without functional decline, and normal allograft function in the absence of histologic evidence of chronic rejection is proposed.Conclusions
It is the intent of this collaborative working group that these working definitions will help to focus ongoing research to define the incidence, risk factors and treatment regimens that will identify mechanisms of chronic rejection in vascularized composite allografts. As with all good research, our initial efforts have generated more questions than answers. We hope that this is the first of many updates.Type
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Kaufman, Christina L, Jean Kanitakis, Annemarie Weissenbacher, Gerald Brandacher, Mandeep R Mehra, Hatem Amer, Bettina G Zelger, Bernhard Zelger, et al. (2020). Defining chronic rejection in vascularized composite allotransplantation-The American Society of Reconstructive Transplantation and International Society of Vascularized Composite Allotransplantation chronic rejection working group: 2018 American Society of Reconstructive Transplantation meeting report and white paper Research goals in defining chronic rejection in vascularized composite allotransplantation. SAGE open medicine, 8. p. 2050312120940421. 10.1177/2050312120940421 Retrieved from https://hdl.handle.net/10161/27255.
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Scholars@Duke

Linda Carime Cendales
Vascularized composite allotransplantation (VCA) refers to the transplantation of multiple tissues, such as skin, muscle, tendon, nerve, and/or bone, as a functional unit (e.g. a hand, an abdominal wall). Several recent advances in clinical organ transplant immunosuppression and experimental VCA have now made it feasible to consider clinical VCA for functional restoration in patients with the loss of one or both hands or large tissue defects that may not be reconstructed with autologous tissue. My research facilitates the translation of VCA from the bench to the bedside.
Our group has established preclinical models to understand VCA rejection in different tissues and to use that insight to minimize immunosuppression in VCA recipients who participate in clinical trials. We also organized the first public international consensus discussions conference in VCA at the Ninth Banff Conference on Allograft Pathology in Spain in 2007 resulting in the Banff VCA 2007 classification for skin allograft pathology. Additionally, we established a VCA Consortium to enable the comprehensive analysis of samples from patients in VCA clinical trials around the country.
Based on our studies of different immunosuppressive regimens in primates, we have been the first to show that belatacept prevents rejection in VCA in primates and controls rejection in humans. We are currently investigating this approach in a clinical trial of hand transplant recipients (NCT02310867). This clinical trial aims to determine the safety and efficacy of hand transplantation as a treatment for patients with limb loss. This study will also test the efficacy of belatacept to prevent rejection of the transplanted hand. We are also currently investigating in a clinical trial the efficacy of abdominal wall transplantation for the reconstruction of abdominal wall defects (NCT03310905).
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