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

Abstract

Objectives: 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.

Graft vasculopathy in upper extremity allotransplantation: Results of a retrospective high‐resolution ultrasonographic study

“…This manifests with myointimal proliferation of arteries, resulting in luminal narrowing and obstruction, producing ischemic-necrotic damage to the graft. 5,12,13 A previous study 12 using ultrasound biomicroscopy showed some degree of GV in all six UET recipients. 12 In that study, the authors used a Vevo 2100 Ultrasound Biomicroscope, which was created for preclinical studies and not to explore adult arteries in clinical practice; moreover, no control group was studied and the precise IMT values were not provided.…”

“…This patient developed clinical signs of CR more than 10 years after the transplantation, manifesting with pain, motor dysfunction, and progressive necrotic skin lesions, leading to graft removal 2 years later. 5 Low-titer circulating anti-class II DSA were detected in this patient transiently from the 6th post-transplant year. Pathological study of the removed UET showed severe GV involving the grafted radial and ulnar arteries, digital arteries, and skin arterioles.…”

“…5 Some additional UET recipients have also reportedly developed GV. 1,[4][5][6]12,13 The vascular lesions reported in these patients were similar to those observed in our patients (myointimal proliferation of arteries). These vascular lesions triggered arterial thrombosis causing in the majority of cases allograft loss from 9 months up to 11 years after transplantation.…”

“…treatment. While it is well known that in UET there is a high incidence of acute rejection (AR) episodes which are easily diagnosed and usually reversed with adequate treatment, 7 currently there is no formal definition and/or classification of chronic rejection (CR), the true incidence of which is not yet well known 5,[8][9][10] although it has been reported in 13.5% of VCA recipients. 4 As in solid organ transplantation, one of the most severe features of CR in VCA is graft vasculopathy (GV), which manifests pathologically with myointimal proliferation of arteries, resulting in luminal narrowing and obstruction, producing ischemic-necrotic damage to the graft.…”

“…6 Although in one of our earlier studies 14 we did not detect signs suggestive of GV in our series of VCA recipients treated with triple immunosuppressive therapy, since then two of these recipients (one with bilateral UET and one with face transplantation) developed GV with consequent graft loss 12 and 10 years after the transplantation, respectively. 5 Some additional UET recipients have also reportedly developed GV. 1,[4][5][6]12,13 The vascular lesions reported in these patients were similar to those observed in our patients (myointimal proliferation of arteries).…”