LIVER AND INTESTINE TRANSPLANTATION

Abstract

The evolution of tacrolimus immunosuppression for recipients of liver allografts has substantiated our belief in the clinical superiority compared to cyclosporine. This was shown in our initial cohort of patients, as well as randomized liver transplant recipients. Results of the multi-center trials conducted in Europe and the United States are congruent with this conclusion. In these randomized trials, crossover from cyclosporine to tacrolimus because of intractable rejection (but not vice versa) was a common event that frequently prevented death or the need for retransplantation. We believe tacrolimus will supplant cyclosporine as the principal baseline immunosuppressive drug for transplantation of the liver and other organs. Not only was there improved patient and graft survivals, but also observed was an improvement in the associated quality of life due to a lower need for steroids, and fewer cosmetic side effects which is of particular importance in the pediatric population. There is a significantly better understanding of not only the mechanisms of tacrolimus but also of a previous epiphenomenon such as “chimerism,” which at the present time we believe is the central event responsible for graft acceptance. The observation of surviving donor multilineage passenger leukocytes being associated with organ graft acceptance implies a persistent engagement of donor and recipient immunocytes with consequent development of various degrees of donor specific non-reactivity. This is of particular importance in recipients of intestinal grafts, where recipient-specific non-reactivity of the chimeric donor cells must occur if the patient is to escape the complication of GVHD. We are presently armed with a new potent immunosuppressive drug, tacrolimus, and an understanding that the migration and grafting of “passenger leukocytes” of bone marrow origin is the seminal explanation for allograft acceptance. The next forefront will involve manipulation of this process not only for the transplantation of already successful whole organs such as liver, kidney, pancreas and heart, but also in the development of the intestinal transplantation program. Thus, augmentation of the leukocyte traffic of unconditioned recipients of cadaver whole organ allografts by the concomitant intravenous infusion of donor bone marrow cells and under the same conditions of immunosuppressive management of tacrolimus/prednisone treatment will be our path into the future.