Pancreas transplantation utilizing thymoglobulin, sirolimus, and cyclosporine.

Background: This study aims to determine the impact of thymoglobulin-sirolimus-cyclosporine immunosuppression on the alloimune response of pancreas-kidney transplant recipients.

Methods: Thirty-six pancreas transplant recipients received an induction protocol of thymoglobulin, sirolimus, reduced-dose cyclosporine, and corticosteroids. Ten recipients were also enrolled in a study to measure immune responsiveness. Flow PRA determined HLA antibody, donor-specific flow cytometry crossmatching (FCXM), T-cell subset, and suppressor cell assays were performed during the first posttransplant year.

Results: One-year patient, kidney, and pancreas graft survivals were 97%, 94%, and 92%, respectively. There was one death and three graft losses. There were no acute rejection episodes. Recipients in the immune-monitoring study (n=10) displayed>80% depression of CD3, CD4, and CD8 (+) cell counts up to 3 months posttransplant. At transplantation 9/10 patients displayed<10% class I and no class II HLA antibody. By 3 months, 7/10 monitored recipients showed a transient elevation in class I HLA antibodies, including 2 patients who expressed>80% Flow PRA. One patient was pretransplant FCXM positive, whereas by 3 months posttransplant 2/10 patients demonstrated a positive FCXM. There were no clinical consequences of the presence of HLA antibody or the positive FCXMs. By 6 months, 7/9 patients demonstrated immunoregulatory suppressor cells.

Conclusions: The absence of acute rejection events was likely due to inhibition of donor-specific immunity by the immunosuppressive regimen. Seventy percent of patients demonstrated an early, non-donor-directed HLA antibody response that had no adverse effect on graft function and 78% of the monitored patients displayed immunoregulatory cells probably contributing to the successful outcomes.