Review of immunosuppressive usage in pancreas transplantation

Throughout 1997, nearly 10 000 pancreas transplants have been performed wor ldwide, with 88% being simultaneous kidney transplants (SKPT). The current 1 yr patient survival rate exceeds 90% and pancreas graft survival (complet e insulin independence) rate exceeds 80% for SKPT, 70% for sequential pancr eas after kidney transplant (PAKT), and 65% for pancreas transplant alone ( PTA). According to registry data, rejection accounts for 32% of graft failu res in the first year after pancreas transplantation. However, improvements are expected to continue with the evolution of treatment protocols. Most p ancreas transplant centers employ quadruple drug immunosuppression with ant i-lymphocyte induction with either a monoclonal or polyclonal antibody agen t. In recent years, there has been an overall decline in the use of antibod y induction therapy from 90% during the period 1987-1993 to 83% of pancreas transplants performed during 1994-1997, Maintenance immunosuppression is t riple therapy consisting of a calcineurin inhibitor (cyclosporine or tacrol imus), corticosteroids, and an anti-metabolite (AZA or MMF). Prior to 1995, nearly all pancreas transplant recipients were managed with Sandimmune, In the last 2 yr, tacrolimus-based therapy has been used in approximately 20% of cases and a new microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in contemporary post-transplant immunosuppression. In a ddition, MMF is replacing AZA as part of the standard immunosuppressive reg imen after pancreas transplantation. At present, a number of centers are co nducting various trials with new drug combinations including either Neoral or tacrolimus in combination with steroids and MMF with or without antibody induction therapy. From 1994 to 1997, the 1 yr rates of immunologic graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The current array of new immunosuppressive agents are providing more effective control of rejection and permitting solitary pancreas transplantation to b ecome an accepted treatment option in diabetic patients without advanced co mplications. The apparent potency of new drug combinations has also resulte d in a resurgence of interest in steroid withdrawal. Immunosuppressive stra tegies will continue to evolve in order to achieve effective control of rej ection while minimizing injury to the allograft and risk to the patient. In addition, new regimens must not only address the issue of specific drug to xicities but also long-term economic, metabolic, and quality of life outcom es. Pancreas transplantation will remain an important alternative in the tr eatment of diabetic patients until other strategies are developed that can provide equal glycemic control with less immunosuppression and overall morb idity.