CLINICAL ISLET TRANSPLANTATION

A.M. Posselt¹, G. Szot², L. Frassetto², U. Masharani², M. Tavakol², F. Vincenti³, L. Fong², J. Bluestone², P. Stock^2
1Transplant Surgery, M896, University of California, San Francisco, San Francisco/CA/UNITED STATES OF AMERICA, ², University of California, San Francisco, San Francisco/CA/UNITED STATES OF AMERICA, ³, UCSF, San Francisco/UNITED STATES OF AMERICA

Body: Background: The applicability of islet transplantation as treatment for type 1 diabetes is limited by the renal and beta cell toxicities of currently available immunosuppressants. We describe two novel immunosuppressive regimens that are based on the anti-LFA 1 antibody efalizumab (EFA) or the costimulation blocking antibody belatacept (BELA) and permit prolonged islet allograft survival without need for corticosteroids or calcineurin inhibitors (CI). Materials and Methods: Ten type 1 diabetics with hypoglycemic unawareness received intraportal allogeneic islet transplants along with 2 doses of thymoglobulin as induction immunotherapy. Maintenance immunosuppression consisted of sirolimus or mycophenolate (MMF), and either EFA (n=5) or BELA (n=5). Glomerular filtration rates (GFR, ml/min/1.73 m²) were measured using iohexol infusion. Results: 5/5 pts who received EFA achieved insulin independence and were weaned off EFA 150 to 420 days ago. 4/5 remain euglycemic on MMF and/or sirolimus; 1 pt has partial function and awaits a second transplant. 5/5 BELA-treated patients became insulin-independent after single transplants; 1 patient resumed partial insulin use 305 days after transplant and is now independent after a second infusion. None of the patients have developed side effects related to the study drugs and all have stable renal function. Immune monitoring of EFA-treated recipients shows increased regulatory T cells and reduced allospecific T cell responses. Conclusions: These two novel immunosuppressive regimens based on EFA or BELA are effective, well tolerated, and the first CI/steroid-free islet protocols resulting in long-term insulin independence. By eliminating CI, these protocols minimize renal and islet toxicity and may thus further improve long-term islet allograft survival and function.

Disclosure: All authors have declared no conflicts of interest.