18-OR

Abstract

Aim Alloreactivity to pancreatic islet cell transplantation (IT) has been reported previously particularly for those IT recipients with a history of sensitization events prior to transplant. The aim of this CIT Consortium study was to determine the incidence of HLA alloimmunization and characterize donor-specific antibody (DSA) profiles after IT. Methods We conducted a prospective, single-arm, Phase III study of IT alone (CIT-07) in T1D in subjects 18 to 65 years of age in 12 transplant centers. Standardized procedures were used for islet manufacturing, patient selection, immunosuppression (Sirolimus, Tacrolimus, Etanercept, Rabbit ATG), transplantation and care. Anti-HLA antibody screening was performed using multiple solid phase assay platforms including the LABScreen® Single Antigen assay at Day 75, Months 6, 9, 12, 18 and 24 after IT. Analyses of antibody specificity included HLA class I (A, B, C) and class II (DR, DQA, DQB, DP). Subjects with HLA antibodies (MFI > 3,000) or pre-transplant DSA (MFI > 700-1,000) were deemed ineligible. CPRA was calculated using an MFI cut off value of 3,000. DSA was defined as bead reactivity with an absolute MFI > 1,000 and an increase in MFI > 50% when compared to pre-IT reactivity. Results Patients received an initial transplant between October of 2008 and September of 2012 Study follow-up will be complete in May of 2014. 48 subjects were transplanted and followed for at least 24 months. 25 of the 48 subjects received a second transplant and 1 subject received a third transplant. An interim analysis through April of 2013 showed that 3/48 (6%) developed DSA while on IS. The PRA remained negative in all patients without DSA. The follow up period ranged from 364 to 1571 days with a median of 736 days. Conclusions The CIT-07 protocol shows a low incidence of PRA or DSA using standardized procedures for islet manufacturing, patient selection and care, and HLA antibody testing. Future studies should evaluate long-term outcomes after DSA development.