Costimulation Blockade in Vascularized Composite Allotransplantation

Abstract

Vascular composite allotransplantation (VCA) is a field under research and has emerged as an alternative option for the repair of severe disfiguring defects that result from infections or traumatic amputation in a selected group of patients. VCA is performed in centers with appropriate expertise, experience and adequate resources to effectively manage the complexity and complications of this treatment. Lifelong immunosuppressive therapy, immunosuppression associated complications, and the effects of the host immune response in the graft are major concerns in VCA. VCA is considered a quality of life transplant and the risk-benefit ratio is dissimilar to life saving transplants. Belatacept seems a promising drug that prolongs patient and graft survival in kidney transplantation and it could also be an alternative approach to VCA immunosuppression. In this review, we are summarizing current literature about the role of costimulation blockade, with a focus on belatacept in VCA.

Sensitization and Desensitization in Vascularized Composite Allotransplantation

“…Other alternative approaches include the use of alemtuzumab and basiliximab ( 34 ). For maintenance immunosuppression, protocols commonly used are derived from solid-organ experience and mainly consist of triple therapy with tacrolimus, MMF and steroids ( 4 , 35 ), There have been reports of management of VCA patients with dual maintenance immunosuppression regimen subsequent to ATG induction ( 36 ). Tacrolimus is the most commonly used calcineurin inhibitor with early (initial period of 1–5 months after transplantation) trough levels of 10–15 ng/mL and 5–10 ng/mL thereafter.…”

“…Vascular composite allotransplantation is an evolving field in organ transplantation since it has emerged as a viable option to repair tissue defects resulting from traumatic or other injuries in selected patients ( 1 ). Vascularized composite allografts (VCAs) consist of anatomically distinct tissues such as skin, muscles, connective tissue, bones and neurovascular elements that are transplanted as a single unit ( 2 – 4 ). So far, VCAs have been used in various settings including transplantation of face, upper or lower extremity, abdominal wall and genitourinary organs ( 4 , 5 ) ( 1 ).…”

“…Vascularized composite allografts (VCAs) consist of anatomically distinct tissues such as skin, muscles, connective tissue, bones and neurovascular elements that are transplanted as a single unit ( 2 – 4 ). So far, VCAs have been used in various settings including transplantation of face, upper or lower extremity, abdominal wall and genitourinary organs ( 4 , 5 ) ( 1 ). As with other solid organ grafts, they are limited by immune mediated rejection and a concomitant requirement for immunosuppression ( 2 – 4 ).…”

“…So far, VCAs have been used in various settings including transplantation of face, upper or lower extremity, abdominal wall and genitourinary organs ( 4 , 5 ) ( 1 ). As with other solid organ grafts, they are limited by immune mediated rejection and a concomitant requirement for immunosuppression ( 2 – 4 ). Also, candidates for VCA are frequently sensitized, making them susceptible for antibody-mediated rejection (AMR).…”

Vascularized composite allotransplants as a mechanistic model for allograft rejection – an experimental study

“…Vascularized composite allotransplants (VCAs) have emerged as means of restoring form and function for selected individuals following devastating injury or limb loss [1]. As with other solid organ grafts, they are limited by immune‐mediated rejection and a concomitant requirement for immunosuppression [2,3]. Although VCA rejection is assumed to be mechanistically similar to the rejection of other organs, several unique features of VCAs are notable from an experimental perspective.…”