Allogeneic islet cell transplantation outcome is improved with smaller transplant size and with addition of etanercept and exenatide to the post-transplant immunosuppression regimen. Chicago researchers from the University of Illinois report that all type 1 diabetics receiving this protocol achieved long-term independence from insulin.
Dr. Jose Oberholzer and colleagues conducted a phase 1/2 study of allogeneic islet cell transplantation in 10 patients with C-peptide-negative type 1 diabetes and hypoglycemic unawareness.
Four patients (Group1) received two to three islet cell transplants with a mean total of 1,460,080 islet cells transplanted, followed by the Edmonton immunosuppression regimen of daclizumab, sirolimus and tacrolimus.
Six patients (Group 2) received one transplant of 537,495 cells, followed by the Edmonton regimen plus the tumor necrosis factor (TNF) receptor blocker etanercept and the glucagon-like peptide-1 (GLP-1) analogue exenatide. The new protocol is known as the University of Illinois regimen.
Patients were followed for 15 months. All patients in both groups became insulin-independent soon after transplantation. In Group 2, two patients resumed insulin – one after a reduction in immunosuppression due to an infectious episode and the other because of exenatide intolerance.
Hemoglobin A1c levels were in the normal range in both groups of patients. Group 1 had a baseline hemoglobin A1c of 6.5, which fell to 5.6 after the series of transplantations. Group 2 had a baseline hemoglobin A1c of 7.8, which fell to 5.8 after one transplantation.
Ryan hypoglycemia severity scores were "markedly" decreased in both groups.
Dr. Oberholzer and colleagues write that "utilization of exenatide and a short course of TNF alpha blockade shows promise in decreasing the need for multiple donors and warrants further investigation."
"This study is extremely promising and shows that we can achieve success with fewer islet cells, freeing patients from the need to check their insulin, even after 20 or 30 years of suffering from diabetes," Dr. Oberholzer says in a University of Illinois press release.
Am J Transplant 2008;8:1250-1261.
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