HLA class I sensitization in islet transplant recipients: report from the Collaborative Islet Transplant Registry.

Pancreatic islet transplantation is a promising treatment option for patients severely affected with type 1 diabetes. This report from CITR presents pre- and posttransplant human leukocyte antigen (HLA) class I sensitization rates in islet-alone transplantation. Data came from 303 recipients transplanted with islet-alone between January 1999 and December 2008. HLA class I sensitization was determined by the presence of anti-HLA class I antibodies. Panel-reactive antibodies (PRA) from prior to islet infusion and at 6 months, and yearly posttransplant was correlated to measures of islet graft failure. The cumulative number of mismatched HLA alleles increased with each additional islet infusion from a median of 3 for one infusion to 9 for three infusions. Pretransplant PRA was not predictive of islet graft failure. However, development of PRA >20% posttransplant was associated with 3.6-fold (p < 0.001) increased hazard ratio for graft failure. Patients with complete graft loss who had discontinued immunosuppression had significantly higher rate of PRA ≥ 20% compared to those with functioning grafts who remained on immunosuppression. Exposure to repeat HLA class I mismatch at second or third islet infusions resulted in less frequent development of de novo HLA class I antibodies when compared to increased class I mismatch. The development of HLA class I antibodies while on immunosuppression is associated with subsequent islet graft failure. The risk of sensitization may be reduced by minimizing the number of islet donors used per recipient, and in the absence of donor-specific anti-HLA antibodies, repeating HLA class I mismatches with subsequent islet infusions.

2008 Update from the Collaborative Islet Transplant Registry.

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>or=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 HbA1c 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.