2007 Update on Allogeneic Islet Transplantation from the Collaborative Islet Transplant Registry (CITR)

Abstract

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.

Impact of Tissue Volume and Purification on Clinical Autologous Islet Transplantation for the Treatment of Chronic Pancreatitis

“…In brief, when the C-peptide value was below the detection level of the assay (0.1 ng/ml), the islet function was defined as “no function.” When a patient achieved insulin independence, the islet function was defined as “full function.” Insulin independence was defined as receiving no exogenous insulin for 2 weeks or longer with excellent glycemic control by cap illary blood glucose measurements, according to the report of the Collaborative Islet Transplant Registry (3). Cases that did not meet the criteria for no function or full function were classified as partial function.…”

Mitigating hypoxic stress on pancreatic islets via in situ oxygen generating biomaterial

“…Clinical islet transplantation provides an attractive approach to restore endogenous insulin control for Type 1 Diabetics [1, 2]. Poor islet engraftment following transplantation, however, significantly hampers long-term islet function; leading to the need for multiple transplants to achieve glycemic control [1, 3].…”

The Efficacy of an Immunoisolating Membrane System for Islet Xenotransplantation in Minipigs

“…However, the chronic need for immunosuppressive therapy following islet transplantation and the persistent shortage of high-quality donor organs is currently restricting this therapeutic approach to a group of high-risk patients who have exhausted conservative treatment options. Indeed, only patients with unstable metabolic control, repeated severe hypoglycemia that is often associated with hypoglycemic unawareness, or those with rapidly progressive diabetes-associated complications are eligible for islet transplantation in most centers [4]. Furthermore, a thorough risk-benefit analysis is required to justify immunosuppressive therapy in patients suffering from a generally non-acute life-threatening disease [5].…”