Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody Mediated Rejection After Vascularized Composite Allotransplantation

ABSTRACT

Close to 40 of combat injuries sustained in Operation Iraqi Freedom and Operation Enduring Freedom involve severe extremity and craniofacial trauma. For many devastating injuries where conventional reconstruction is not possible, vascularized composite allotransplantation (VCA) has become a viable alternative, providing new, exciting options for Wounded Warriors that could better restore the appearance, anatomy, and function. However, clinical management of these injuries prior to reconstruction frequently requires multiple blood transfusion or skin allografts resulting in the formation of alloantibodies (anti-HLA IgG Abs, donor specific antibodies or DSA) and a high degree of sensitization. The role of DSA and mechanisms of antibody mediated rejection (AMR) in VCA are still largely unknown. To date, there is only one single experimental study published that has recently attempted to define the role of DSA in a rat model of vascularized osteomyocutaneous flap allotransplantation. As such, this project aims to comprehensively investigate the mechanisms and impact of pre-existing and de-novo DSA and AMR in in VCA. The goal is to develop a clinically translatable desensitization protocol that will subsequently broaden the eligible population for reconstructive transplantation to include those patients who have become sensitized to foreign antibodies