2008 Update From the Collaborative Islet Transplant Registry Rodolfo Alejandro, 1 Franca B. Barton, 2,4 Bernhard J. Hering, 3 and Steve Wease 2 ; The CITR Investigators Background. This report summarizes the primary efficacy and the safety outcomes of islet transplantation reported to the NIDDK and JDRF funded Collaborative Islet Transplant Registry (CITR), currently the most comprehensive collection of human-to-human islet transplant data. Methods. CITR collects and monitors comprehensive data on allogeneic islet transplantation in North America, Europe, and Australia since 1999. Results. As of April 2008, the CITR registry comprised 325 adult recipients of 649 islet infusions derived from 712 donors. At 3 years post-first infusion, 23% of islet-alone recipients were insulin independent (II2 weeks), 29% were insulin dependent with detectable C-peptide, 26% had lost function, and 22% had missing data. Seventy percent achieved II at least once, of whom 71% were still II 1 year later and 52% at 2 years. Higher number of infusions, greater number of total islet equivalents infused, lower pretransplant HbA 1c levels, processing centers related to the transplant center, and larger islet size are factors that favor the primary outcomes. Protocols with daclizumab or etanercept during induction had higher rates of II and lower rates of function loss, which endorse the current approaches. Infusion-related adverse event incidence was 0.71 events/person-year (EPY) in year 1, whereas immunosuppression-related adverse event incidence was 0.87 EPY, both declining to less than 0.21 EPY thereafter. Conclusions. Clinical islet transplantation needs to be evaluated using the most clinically relevant endpoints such as glucose stabilization and severe hypoglycemia prevention. The cumulative results of the registry confirm the inarguably positive impact of islet transplantation on metabolic control in T1 diabetes. Keywords: Islet transplantation, T1 Diabetes, Immunosuppression. (Transplantation 2008;86: 1783–1788) H uman-to-human transplantation of islets of Langerhans is an evolving therapy for persons with T1 diabetes (T1D) and severe hypoglycemia or T1D after kidney trans- plant. The Edmonton protocol of nonsteroidal immunosup- pression (1, 2) has encountered challenges in reproducibility of results and durability of clinical benefit (3). The various immunosuppressive regimens generally have not been evalu- ated in randomized comparisons. With a world-wide collec- tive experience to date of only approximately 700 recipients, factors that influence outcomes are difficult to identify. Fur- thermore, the supply of human islets remains severely lim- ited. Nonetheless, the quest for the best recipients and best regimens for islet preparation and immunosuppression continues. To date, the most complete collection of information on islet transplantation comes from the Collaborative Islet Transplant Registry (CITR) funded by the NIDDK and the JDRF. This report summarizes results from the fifth CITR Annual Report (4) on recipients of one or more islet cell transplants between 1999 and 2007 inclusive. Twenty-five of 31 US/Canadian medical institutions, active in islet transplantation since 1999, participated in the Registry. Data from two JDRF-sponsored European centers are also included. PATIENTS AND METHODS Patients and methods are fully described in the CITR Annual Report (4). Briefly, recipients of allogeneic islet trans- plants have T1 diabetes mellitus for more than 5 years, are between 18 and 65 years of age, and have poor diabetes con- trol including episodes of severe hypoglycemia and hypogly- cemia unawareness, wide swings of blood glucose levels, or consistently high HbA 1C levels (8%). The registry collects information on the pancreas donor(s), islet processing and testing, immunosuppression and concomitant medications, severe hypoglycemic episodes, hemoglobin A 1C , fasting blood glucose and C-peptide, daily insulin status, vital status, re- portable adverse events (AEs), islet graft dysfunction and loss, donor and islet processing data, all AEs graded 3, 4, and 5 according to the terminology criteria for adverse events of the Clinical Islet Transplantation Consortium (5), and all serious AEs (6). The data are rigorously monitored to comply with 21 Code of Federal Regulations (CFR) requirements. The data- base was closed for analysis on April 1, 2008 for data on re- cipients that were registered in CITR as of December 31, 2007. Site participation in the registry requires local research ethics board approval and written informed consent by the islet recipients. The CITR Publications and Presentations Committee approved the manuscript. The Collaborative Islet Transplant Registry is funded by a grant from the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA, and by a supplemental grant from the Juvenile Diabetes Foundation International. Additional data are made available through cooperative agreements with the US United Network for Organ Sharing and the Administrative and Bioinformatics Coordinating Center of the City of Hope. The CITR investigators contributing data to this report are listed in the Appendix. 1 The Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL. 2 The EMMES Corporation, Rockville, MD. 3 Diabetes Institute for Immunology and Transplantation, University of Minnesota, Minneapolis, MN. 4 Address correspondence to: Franca B. Barton, M.S., The EMMES Corpo- ration, Rockville, MD. E-mail: fbarton@emmes.com Received 7 August 2008. Revision requested 11 September 2008. Accepted 13 October 2008. Copyright © 2008 by Lippincott Williams & Wilkins ISSN 0041-1337/08/8612-1783 DOI: 10.1097/TP.0b013e3181913f6a Transplantation • Volume 86, Number 12, December 27, 2008 1783