Excellent outcomes can be achieved in young pancreas transplant alone recipients by addition of sirolimus to maintenance immunosuppression regimen

Background: Pancreas transplant alone (PTA) has evolved into a viable treatment option for nonuremic patients with labile diabetes mellitus. Historically, PTA outcomes were inferior to simultaneous pancreas-kidney transplant outcomes, because of the higher rate of graft loss due to rejection in PTA recipients. But with advances in immunosuppression, PTA outcomes have improved significantly--except in young PTA recipients. The more potent immune system in young recipients appears to play a key role. In this study, our objective was to investigate outcomes of PTA, by recipient age, with the use of different immunosuppressive maintenance regimens.

Methods: Using information from the International Pancreas Transplant Registry and from the United Network for Organ Sharing, we analyzed outcomes of 393 technically successful enteric-drained transplants in the PTA category that were performed from January 2003 through December 2012. All PTA recipients underwent induction immunosuppression with thymoglobulin and pulse steroids and were then maintained on long-term low-dose prednisone. Excluded from our study group were patients who experienced surgical graft loss. We divided the 393 recipients into 2 age groups: <42 years (187 patients) versus ≥42 years (206 patients). For both the younger group and the older group, we compared 2 maintenance immunosuppressive regimens: (1) tacrolimus (Tac) and mycophenolate mofetil (MMF) versus (2) Tac/MMF and sirolimus (Srl). We refer to immunosuppression with Tac and MMF as the non-Srl regimen.

Results: The overall 3-year graft survival rate, across both age groups, was significantly better with the Srl regimen (P = .03). Regardless of the immunosuppressive regimen used, outcomes were significantly better in the older group than in the younger group (P = .05). In the older group, with both regimens, outcomes were similar (P = .55). But in the younger group, outcomes with the Srl regimen were significantly better (P = .009) than with the non-Srl regimen and, in fact, were similar to outcomes in the older group.

Conclusions: Our study shows that adding Srl to the standard maintenance immunosuppressive regimen of Tac and MMF provides the best outcomes in young PTA recipients, the most immunologically robust and therefore the most immunologically challenging age group. To achieve excellent outcomes, more potent immunosuppression is required in this cohort. We think that PTA should be offered to young patients with labile diabetes before secondary complications develop.