We sought to determine the long-term outcomes in type 1 diabetic recipients of intraportal alloislet transplants on a modified immunosuppressive protocol. Six recipients with hypoglycemia unawareness received 1 to 2 islet infusions. Induction therapy was with antithymocyte globulin (ATG) plus etanercept for tumor necrosis factor-α blockade. Recipients received cyclosporine and everolimus for maintenance immunosuppression for the first year posttransplant, with mycophenolic acid or mycophenolate mofetil subsequently substituted for everolimus. Recipients have been followed for 1173 ± 270 days since their last infusion for islet graft function (insulin independence, hemoglobin A1c levels, and C-peptide production) and for adverse events associated with the study protocol. Of the 6 recipients, 5 were insulin-independent at 1 year, and 4 continue to be insulin-independent at a mean of 3.4 ± 0.4 years posttransplant. None of the 6 recipients experienced recurrence of severe hypoglycemia. Measured glomerular filtration rate decreased from 110.5 ±21.2 mL/min/1.73m2 pretransplant to 82.6 ±19.1 mL/min/1.73m2 at 1 year posttransplant. In conclusion, islet transplants restored insulin independence for a mean of >3 years in 4 of 6 recipients treated with ATG and etanercept induction therapy and with cyclosporine and, initially, everolimus for maintenance. Our results suggest this immunosuppressive protocol may allow long-term graft survival.

As of October 1, 2007, 25 North American medical institutions and one European islet transplant center reported detailed information to the Registry on 315 allograft recipients, of which 285 were islet alone (IA) and 30 were islet after kidney (IAK). Of the 114 IA recipients expected at 4 years after their last infusion, 12% were insulin independent, 16% were insulin dependent with detectable C-peptide, 40% had no detectable C-peptide, and 32% had missing C-peptide data or were lost to follow-up. Of the IA recipients, 72% achieved insulin independence at least once over 3 years and multiple infusions. Factors associated with achievement of insulin independence included islet size >1.0 expressed as IEQs per islet number [hazard ratio (HR) = 1.5, p = 0.06], additional infusions given (HR = 1.5, p = 0.01), lower pretransplant HbA(1c) (HR = 1.2 each %-age unit, p = 0.02), donor given insulin (HR = 2, p = 0.003), daclizumab given at any infusion (HR = 1.9, p = 0.06), and shorter cold storage time (HR = 1.04, p = 0.03), mutually adjusted in a multivariate model. Severe hypoglycemia prevalence was reduced from 78-83% preinfusion to less than 5% throughout the first year post-last infusion, and to 18% adjusted for missing data at 3 years post-last infusion. In Year 1 post-first infusion for IA recipients, 53% experienced a Grade 3-5 or serious adverse event (AE) and 35% experienced a severe AE related to either an infusion procedure or immunosuppression. In Year 1 post-first infusion, 33% of IA subjects and 35% of IAK subjects had an AE related to the infusion procedure, while 35% of IA subjects and only 27% of IAK subjects had an AE related to the immunosuppression therapy. Five deaths were reported, of which two were classified as probably related to the infusion procedure or immunosuppression, and 10 cases of neoplasm, of which two were classified as probably related to the procedure or immunosuppression. Islet transplantation continues to show short-term benefits of insulin independence, normal or near normal HbA(1C) levels, and sustained marked decrease in hypoglycemic episodes.