Association of Primary Graft Function and 5-year outcomes of islet transplantation: An international study from the Collaborative Islet Transplant Registry (CITR)
Mikael Chetboun1, Cassandra Ballou2, Elodie Drumez1, Franca Barton2, Elizabeth Payne2, Francois Pattou1.
1CHU Lille, Lille Pasteur Institute, Inserm, F-59000, Univ. Lille, CHU Lille, Lille, France; 2CITR, The EMMES Corporation, Rockville, MD, United States
On behalf of the Collaborative Islet Transplant Registry (CITR) publication committee.
Introduction: Islet graft function following allogenic islet transplantation (IT) in type 1 diabetes (T1D) declines with time. The impact of initial islet graft function as opposed to recipient characteristics or immunosuppression regimen on long-term success of IT is unclear. In this registry study, we explored the association between primary islet graft function (PGF) and 5-year outcomes of allogenic IT.
Method: Participants were T1D patients with hypoglycemia unawareness (ITA) and/or a functioning kidney graft (IAK), who were enrolled in the CITR, after receiving at least one allogenic intraportal islet infusion. Exposure of interest was PGF, measured 28 days post last infusion with the beta2-score (B2S), and explored as continuous or qualitative variable (quartiles classes). Primary outcome was loss of IT success defined by the EPITA-IPITA Igls 2.0 criteria : HbA1c <7% without SHE with fasting C-peptide ≥ 0.2 ng/mL. Secondary outcomes were the loss of graft survival (C-peptide ≥ 0.3 ng/mL) and the loss of insulin independence. The association between PGF and IT outcomes were analyzed during 5 years by survival analysis taking into account death and iterative islet infusion (≥ 1 year after last infusion) as competing events after handling missing values by multiple imputations (m=20) and adjusted on prespecified covariates suspected or known to impact IT (age, gender, BMI, diabetes duration, insulin requirements and fasting C-peptide value before IT, number of islet infusion, total islet mass and total cell volume transplanted, type of recipient, immunosuppression).
Results: From 1996 to 2019, 1121 patients with a mean history of T1D of 30.7 ± 11.2 yrs ,aged of 47.1 ± 10.3 yrs, including 490 (40.5%) males received IT by 1.7 ± 0.7 infusions and a mean total islet mass of 746.2 ± 343.2 103 IEQ. Among them 215 (17.8%) were IAK recipients. Mean PGF was 14.2 ± 8.8. Overall 76 % (74-79), 42 % (39-45), and 71 % (67-74) of participants had failed IT success, graft survival, and insulin independence at 5 years, respectively, respectively (cumulative incidence). PGF was negatively associated with the primary and secondary endpoints, with Hazard Ratio of 0.77 (0.73 to 0.82), 0.64 (0.58 to 0.70), and 0.77 (0.73 to 0.80) respectively (p<0.001; per 5 units increase of B2S). When PGF was analyzed by quartile classes, there was a dose effect between increase in PGF and all 5-year outcomes of IT.
Conclusion: Based on the CITR analysis of 1121 islet recipients, we observed an independent positive relation between PGF and 5-year success of IT.
The authors are indebted to The CITR funded by the NIDDK, the National Institutes of Health and by the JDRF International.