Clinical experience with autologous and allogeneic pancreatic islet transplantation.

Abstract

Background. We initiated a pancreatic islet transplantation program using fresh, single-donor tissue. Methods. Group 1 (n=3) received cadaver kidney and islets from the same donor; islets were placed beneath the capsule of the transplanted kidney. Group 2 (n=6) received islets via percutaneous portal vein puncture subsequent to successful kidney transplant. Group 1 and 2 recipients had type 1 diabetes mellitus. Group 3 (n=6) received autologous islet transplantation after total or near-total pancreatectomy (for chronic pancreatitis and intractable pain). Implantation and graft function was considered successful if C-peptide exceeded 0.10 ng/ml. Sustacal challenge test was done before and after transplant at day 1, week 1, and months 1, 3, 6, and 12. We also measured glycated hemoglobin and insulin requirements at regular time intervals. Results. Post-Ficoll yield was 402,000 (SD 174,000) equivalent islet number, average purity of 67% (range, 50-90%). Group 1 had initial primary nonfunction followed by occasional evidence of C-peptide at months 3 and 6. Group 2 recipients had significant C-peptide levels early after transplantation which gradually declined over several months. However, all recipients had graft function at 6 months and 50% recipients still maintained graft function at 1 year. Group 3 recipients are off exogenous insulin (mean follow-up of 5.5 months). Insulin requirement was unchanged in group 1, while a reduction of approximately 20% was noted in four of six patients in group 2. Glycated hemoglobin was reduced in four out of six recipients of group 2, while in group 3, glycated hemoglobin remained within normal limits. Pain relief was sustained when patients (group 3) received total pancreatectomy; near-total pancreatectomy resulted in recurrence of pain within 3 months. Conclusions. Autologous islet transplantation is uniformly successful; total excision of pancreas was superior to partial pancreatectomy for pain relief. For allogeneic islet transplantation, the intrahepatic site is superior to the renal subcapsular site. Insulin independence was not achieved in allogeneic islet transplants; however, continued graft function resulted in reduction of glycated hemoglobin in some recipients.