Mortality after Steroid Resistant Acute Cellular Rejection and Chronic Rejection Episodes in Adult Intestinal Transplant: Report from a Single Center in Induction/Preconditioning Era

Abstract

Aim: Steroid resistant ACR and chronic rejection (CR) are still a major concern after intestinal transplantation, especially using grafts without liver: over last 20 years the presence of liver has been shown to have a protective effect on rejection episodes. We report our experience from a single center on adult recipients. Subjects and Methods: We transplanted 48 adult recipients using 49 grafts, from 2001 up to 2011: 85.7% of them were represented by grafts without liver (isolated or modified multivisceral allografts). Induction protocol was used initially on 12 transplants, accomplished by Daclizumab plus Tacrolimus and Steroids, while later we developed a preconditioning protocol, based on Alemtuzumab plus Tacrolimus, on 35 allografts; in 2 cases we preconditioned the recipients by Thymoglobulin followed by Tacrolimus. Results: Overall patient survival was 41.5 % at 10 years while graft survival was 39%. Steroid resistant ACR population: 13 recipients experienced episodes of steroid resistant ACR. Three of them were successfully treated by OKT3, 1 by Alemtuzumab and 1 by Thymoglobuline, while 1 case underwent re-transplantation after OKT3 treatment. Seven recipients died after ACR therapy mainly for sepsis: 2 after Thymoglobulin, 2 with OKT3, 1 after Infliximab, and 2 after combined treatment (Alemtuzumab plus Thymoglobulin and Thymoglobulin plus Infliximab). Twelve allografts out of 13 were grafts without liver. Chronic rejection population: 5 recipients were affected by CR (1 of them primarly transplanted in another center): 4 of them experienced indeterminate to mild episodes of ACR (only one as early as 30 days after transplant) before developing CR while only 1 had a severe episode of rejection. Two of them are still alive: 1 underwent graftectomy without increasing immunosuppressive treatment and was relisted on TPN while 1 recovered oral feeding (supported by TPN) after partial bowel resection plus stoma. The remnant 3 patients died for sepsis, 1 after retransplantation. Majority of them had mesenteric fibrosis as main pathologic feature of CR and diagnosis was always performed on resected specimen. Overall mortality: Steroid resistant ACR mortality was 50% while CR mortality was 60%: overall, 10 patients out of 19 (52.6%) died after steroid resistant ACR or CR. Notably, mortality after Daclizumab was 17.7% in steroid resistant ACR and CR population while after Alemtuzumab the percentage achieved 28.8%. The remnant transplant population (no ACR or steroid sensitive ACR - 27 patients) was affected by mortality percentage of 40.7% (p= NS). Conclusions: In our series steroid resistant ACR affected 29.1 % of our intestinal allografts (all but one without liver) while CR was shown on 8% of our resected bowels, all isolated grafts: CR was often preceded by ACR episodes. Mortality related to steroid resistant ACR and CR still affects intestinal transplant population in induction/preconditioning era.