DONOR-SPECIFIC PORTAL BLOOD-TRANSFUSION IN INTESTINAL TRANSPLANTATION- A PROSPECTIVE, PRECLINICAL LARGE ANIMAL STUDY

Background Unlike in kidney and heart transplantation, the role of pre transplant donor-specific blood transfusion (DST) has not been studied prospectively in a large animal model of bowel transplantation. We in vestigated the impact of portal versus systemic DST on overall surviva l, rejection, graft-versus-host disease (GVHD), and infection after to tal (small and large) bowel transplantation in pigs. Methods. Mixed ly mphocyte culture-reactive, outbred pigs underwent total enterectomy an d orthotopic total bowel transplantation with portal vein graft draina ge. One unit of donor blood was transfused via the portal or systemic circulation (according to a randomization protocol) before graft impla ntation was begun. We studied six groups,, all of which underwent at l east a total bowel transplant: group 1 (n=5) comprised nonimmunosuppre ssed control pigs with portal DST; group 2 (n=6), nonimmunosuppressed control pigs with systemic DST; group 3 (n=5), cyclosporine (CsA)-trea ted pigs with portal DST; group 4 (n=5), CsA-treated pigs with systemi c DST; group 5 (n=5), tacrolimus-treated pigs with portal DST; and gro up 6 (n=5), tacrolimus-treated pigs with systemic DST. All immunosuppr essed pigs received prednisone (2 mg/ kg/day) and either CsA (to maint ain levels between 250 and 350 ng/ml) or tacrolimus (to maintain level s between 10 and 30 ng/ml). Stomal biopsies and autopsies were obtaine d to study the incidence of rejection, GVHD, and infection. Results. P ortal DST and tacrolimus-based immunosuppression resulted in the highe st survival rates. At 7, 14, and 28 days after transplantation, surviv al rates in group 5 were 100%, 100%, and 80%; in group 6, 100%, 60%, a nd 40%; and in group 3, 100%, 0%, and 0%, respectively. Only the combi nation of portal DST and tacrolimus prevented the occurrence of, and d eath from, rejection. Death from rejection at 7, 14, and 28 days in gr oup 5 was 0%, 0%, and 0%; in group 6, 0%, 33%, and 67%; and in group 3 , 0%, 100%, and 100%, respectively. Of note, if immunosuppression was used, the groups with portal (versus systemic) DST had a higher risk o f death from infection but a lower risk of death from GVHD. Simultaneo us immunologic events were noted more frequently in groups with system ic (versus portal) DST. Long-term survival was noted only in groups wi th tacrolimus-based immunosuppression and was more common for those wi th portal (versus systemic) DST. Conclusions. Portal DST at the time o f total bowel transplantation and posttransplant immunosuppression wit h tacrolimus prevent rejection and significantly increase graft surviv al. The combination of portal antigen presentation and tacrolimus need s to be studied in clinical bowel transplantation.