Primary Graft Function Predicts 5-Year Islet Transplantation Outcomes in T1D

Primary graft function is a reliable surrogate endpoint for allogeneic islet transplantation success in patients with severe hypoglycemia, according to study findings in the Lancet Diabetes Endocrinology.

Treatment with an allogeneic pancreatic islet transplantation is an already approved form of therapy for patients with type 1 diabetes. Due to the eventual decline of the transplanted islet graft function, researchers conducted a multicenter, observational cohort study to assess the association between primary graft function and 5-year islet transplantation outcomes. The 5-year islet graft outcomes were then used to develop a predictive model. The primary outcome was the total incidence of unsuccessful islet cell transplantations, defined by criteria from the International Pancreas and Islet Transplant Association (IPITA) and European Pancreas and Islet Transplant Association (EPITA) Igls 2.0 consensus.

The researchers used data from the Collaborative Islet Transplant Registry (CITR) from January 1999 and July 2020. Patients with type 1 diabetes who received islet transplantation alone to treat severe hypoglycemia as well as patients with an islet-after-kidney transplant who received at least 1 perfusion were included.

A total of 1376 patients who received at least 1 allogeneic pancreatic islet infusion were identified from the CITR database. After exclusions, 1210 patients remained for analysis and were followed up for up to 5 years after the initial follow-up 28 days after transplantation. Patients were aged an average of 47 years (standard deviation [SD], 10), the majority were female (59.5%) and White (97.9%), and patients had an average diabetes duration of 30.4 years (SD, 11.2). Of those included in the study, 452 (37.4%) underwent a single islet infusion and 758 (62.6%) received more than 1 infusion. Among those who received multiple infusions, most patients received the next infusion within 6 months of their first (70%).

The researchers found the average primary graft function at day 28, measured using the BETA-2 score, was 14.3 (SD, 8.8). The average primary graft function in patients with a single infusion was 10.1 (SD, 7.9), compared to 16.8 (SD, 8.4) among patients receiving multiple infusions. Patients who received islet transplantation alone had an average primary graft function of 13.9 (SD, 8.6) compared with 16.2 (SD, 9.5; P =.0016) among patients who received islet-after-kidney transplants.

Upon assessment of mortality and delayed islet reinfusion, researchers reported that 19.6% of recipients had unsuccessful transplants 28 days after infusion (95% CI, 17.2-22.2). Among these patients, the median primary graft function was 5.0 (IQR, 0.6-11.8).

After adjusting for covariates and missing data, primary graft function was inversely related to failure of islet transplantation per 5-unit increase of the BETA-2 score (adjusted sub hazard ratio [aSHR], 0.77; 95% CI, 0.72-0.82; P <.0001). Patients who had a primary graft function in the 75th percentile (>20.1) had a lower risk of unsuccessful islet transplantation compared with a primary graft function in the 25th percentile (aSHR, 0.35; 95% CI, 0.26-0.45; P <.0001).

Study limitations included a lack of documentation for repeated islet infusion, lack of assessment on transplantation complications, and limited availability of donor pancreases.

“To improve the outcome of current strategies for β-cell replacement, more attention should be directed to evaluate and optimise early islet graft potency by enhancing the survival and function of transplanted islets or other insulin-secreting cells,” the researchers concluded.