Report on the Alberta Foundation's Successful Islet Transplants
Dr. James Shapiro and collaborators at the University of Alberta in Edmonton, Canada, reported the first successful series of islet cell transplants in patients with type 1 diabetes. The presentation was made at the annual meeting of the American Society of Transplant Surgeons and the American Society of Transplantation in Chicago (the abstracts of the meeting are available on-line at www.transplant2000.org). The Edmonton group reported the results in 8 patients who received islet transplants with a new steroid free regimen based on a combination of recently introduced anti rejection drugs (anti IL2 receptor humanized antibody and rapamicin) that allowed to use a low dose of FK-506 (tacrolimus)and no steroids at all. All patients are insulin free at variable times after transplantation, up to over 14 months post islet cell infusion.
These results look really promising and represent the first consecutive series of successful islet cell transplants in patients with type 1 diabetes. In 1990, we performed the first successful series of islet cell transplants in patients with surgical diabetes (published in Lancet, 1990) using FK-506 as base immunosuppression and no steroids. Since then, it has been very challenging to reproduce the same results in patients with type 1 diabetes. This was in part due to the fact that the islet cell transplants have been generally performed in combination with another organ transplant and the anti rejection drugs used were the one chosen for the organ, which were not necessarily good for the transplanted islets. In fact, the anti rejection drugs generally used (e.g., cyclosporine, tacrolimus, steroids) are toxic to the transplanted islets and can induce diabetes even in patients who are receiving other organ transplants and who are not diabetic to begin with. This new anti rejection protocol allowed the Edmonton group to perform two islet transplants within several weeks from each other. The first transplant improved diabetes control and reduced insulin requirements, smilarly to what we and others have observed in the past. The second islet transplant resulted in freedom from insulin injections in all cases. These unprecedented results are reason for optimism in the islet cell transplant field and a multicenter trial is now planned to test and reproduce the Edmonton protocol. This trial will include 8 centers in Europe and North America, in a collaborative effort to implement this islet transplant protocol in 32 additional islet cell transplant recipients.
The outstanding results of the Edmonton group confirmed the feasibility and potential of islet transplantation. However, it must be remembered that the protocol still required a very powerful anti rejection therapy that was needed to prevent immune destruction of the transplanted islets. This protocol will not be offered to all patients with type 1 diabetes, but will be initially limited to patients at higher risk, such as patients with difficult to control diabetes and/or hypoglycemia unawareness, in which it is justified to consider exposure to life-long immunosuppression (anti rejection drugs).
Our center and others including Edmonton will continue to concentrate research efforts towards the development of strategies that will allow to transplant islets from a single donor pancreas and without the long term requirement for anti rejection drugs.
Camillo Ricordi, MD
Surgeon, Islet Transplantation Research
Diabetes Research Institute
University of Miami School of Medicine
Posted June 4, 2000
Updated May 31, 2002
Last Updated: Thursday August 29, 2002 20:59:48
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