Islet Transplantation at the University of Alberta: Status Update and Review of Progress over the Last Decade

Abstract

Keywords: islet transplant type 1 diabetes hypoglycemia immunosuppressionMots clés: transplantation d'îlots diabète de type 1 hypoglycémie immunosuppression a b s t r a c tThe general perception of islet transplantation among the diabetes community is somewhat negative, as insulin independence was maintained in only a small minority and there are fears about the safety of lifelong immunosuppression. There has been substantial progress in refining the islet transplant procedure to enhance its safety, reduce the toxicity of immunosuppression and improve long-term graft function. Longer-term follow-up studies have clarified the indications for islet transplantation; frequent, severe hypoglycemia, hypoglycemia unawareness and glycemic lability; facilitated informed consent and provided a framework for more realistic expectations, and suggest beneficial effects on microvascular complications. One hundred thirty-eight individuals have undergone islet transplantation at the University of Alberta over the last 12 years. Of these, 109 (79%) have full or partial graft function. Patient survival is 96% with no deaths due to transplantation. Three subjects have been hospitalized because of severe opportunistic infection and 3 have progressed to require renal replacement therapy. Current protocols are able to achieve insulin independence rates of 60% beyond 4 years. Safer and more effective islet transplantation, along with refinements in immunosuppressive therapy, make islet transplantation a more attractive option for a subset of persons with type 1 diabetes who suffer from frequent, severe hypoglycemia, lability and/or hypoglycemia unawareness, and resulting in excellent glycemic control and freedom from hypoglycemia.Ó 2012 Canadian Diabetes Association r é s u m é L'opinion générale de la communauté diabétique sur la transplantation d'îlots est quelque peu négative, comme l'insulino-indépendance est maintenue par un petit nombre seulement et qu'il y a des craintes concernant l'innocuité de l'immunosuppression permanente. Des progrès considérables quant au raffinement de la technique de transplantation d'îlots ont eu pour effet d'améliorer son innocuité, de réduire la toxicité de l'immunosuppression et d'améliorer le fonctionnement du greffon à long terme. Les études de suivi à plus long terme ont précisé les indications de la transplantation d'îlots (hypoglycémie grave et fréquente, ignorance de l'hypoglycémie et instabilité glycémique), facilité le consentement informé et fourni un cadre pour des attentes plus réalistes, et elles laissent entrevoir des effets bénéfiques concernant les complications microvasculaires. Cent trente-huit individus (138) ont subi une transplantation d'îlots à l'Université de l'Alberta au cours des douze dernières années. Parmi eux, 109 (79 %) ont un fonctionnement du greffon complet ou partiel. La survie des patients est de 96 % sans décès attribués à la transplantation. Trois (3) sujets ont été hospitalisés en raison d'infection opportuniste grave et 3 ont évolué vers la thérapie de remplacem...

Posttransplant Lymphoproliferative Disorder After Clinical Islet Transplantation: Report of the First Two Cases

“…insulin secretion in highly selected subjects with type 1 diabetes (T1D) (13). In contrast to the original "Edmonton Protocol," which used sirolimus for immunosuppression, our standard steroid-sparing immunosuppression regimen uses tacrolimus and mycophenolate mofetil (MMF) (17). Islet transplantation provides excellent glycemic control and robust protection from severe hypoglycemia (15).…”

“…Lymphocyte-depleting induction agents, such as alemtuzumab or thymoglobulin, have become standard of care in many centers because of superior graft outcomes (16). In contrast to the original "Edmonton Protocol," which used sirolimus for immunosuppression, our standard steroid-sparing immunosuppression regimen uses tacrolimus and mycophenolate mofetil (MMF) (17). Antiviral prophylaxis followed by weekly monitoring or pre-emptive management is used depending on donorrecipient EBV and cytomegalovirus (CMV) serostatus and exposure to lymphodepleting agents (18).…”

Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges

“…In 2013 alone, 66 islet transplants were conducted at the Edmonton site. The Edmonton group also reports that of over 200 patients transplanted with more than 400 intraportal islet preparations, 79% of recipients continue to show full or partial islet graft function 20. The median duration of insulin independence is 34.6 and 11 months for subjects with full or partial graft function, respectively, whereas the duration of C-peptide is 53.3 and 70.4 months, respectively, for those same patients 20–22…”

Pancreas Versus Islets After a Successful Kidney Transplant

“…Of over 200 patients transplanted with more than 400 intraportal islet preparations, the Edmonton group reports that currently 79 % of patients continue to show full or partial islet graft function [61•]. The median duration of insulin independence is 34.6 and 11 months for subjects with full or partial graft function, whereas the duration of C-peptide is 53.3 and 70.4 months for those same patients [5,62,63].…”