2578: Improved vascularized composite allograft survival in sensitized rats after syngeneic hematopoietic stem cell transplantation and fludarabine

Abstract

2578: Improved vascularized composite allograft survival in sensitized rats after syngeneic hematopoietic stem cell transplantation and fludarabine Howard D. Wang, MD, Samuel Fidder, MD, Devin Miller, MD, Georg Furtmuller, MD, Denver M. Lough, MD, PhD, Joseph Lopez, MD, MBA, Amy Quan, MPH, Joshua Budihardjo, Giorgio Raimondi, PhD, Zhaoli Sun, MD, PhD, W. P. Andrew Lee, MD, and Gerald Brandacher, MD Johns Hopkins University School of Medicine, Vascularized Composite Allotransplantation (VCA) Laboratory, Baltimore, MD, USA Background Vascularized composite allotransplantation (VCA) is a promising option for patients with devastating injuries from severe burn or trauma The initial management of this patient population frequently requires blood transfusions or skin allografts, leading to formation of alloantibodies and a high degree of sensitization Sensitized recipients are at risk for antibody-mediated rejection (AMR) and poor graft outcomes Our group has established a model of AMR in sensitized rats and demonstrated accelerated rejection of the hind-limb allograft The aim of this study is to establish a desensitization protocol using haematopoietic stem cell transplantation (HSCT) to prevent AMR in the setting of VCA. Methods Sensitization was established by performing skin transplants from Dark Agouti (DA) donors to Lewis rat recipients Sensitized controls received skin transplant only, whereas the experimental group underwent a desensitization protocol including a 7-day course of fludarabine, myeloablative total body irradiation (12Gy) and syngeneic HSCT Serum donor specific antibody (DSA) levels of both groups were measured using flow cytometry after skin transplant and again after desensitization Orthotopic hind-limb transplantation from DA donors was then performed, and daily tacrolimus (05 mg/kg) was administered thereafter Graft rejection was defined as grade 3 rejection and was assessed by clinical monitoring and histology Complement deposition was examined by performing immunohistochemistry for C4d.