From Vancouver, British Columbia, Canada:
In September 1989, a woman at the University of Alberta had an islet cell transplant. It was stated to be "The Cure" if she remained insulin-free for 5 years. It has now been 10 years and I can't find any information. What has been the results, and when will it be available to other patients (for example: my 7 year old son)?
A renewed, although cautious optimism has recently emerged in the area of clinical islet transplantation for the treatment of type 1 diabetes, as a result of proof-of-concept in over 40 surgical and type 1 diabetic patients who have become insulin-independent following adult islet allotransplantation. One recipient has now been insulin-independent for five years and others have had functioning grafts for over 8 years.
Islet tissue has been generally obtained from cadaveric organ donors, the majority of transplants have been performed in conjunction with vascularized organ allografts, the most frequent transplant site has been the liver, and recipient treatment generally included inductive course of antilymphocyte globulin, followed by T-cell directed maintenance immunosuppression.
Simultaneous islet-liver allotransplantation following upper abdominal exenteration, including total pancreatectomy, was first explored by the Pittsburgh/Miami group in 1990 and has since been performed worldwide in a total of 15 patients suffering from primary or secondary hepato-biliary malignancies. Additional transplants in this recipient category were not undertaken after 1995. Nearly all patients in this recipient category eventually expired with recurrent metastatic disease while still being insulin-independent. The longest duration of insulin independence was noted in the first Pittsburgh patient who died of recurrent malignancy while being normoglycemic and insulin independent almost 5 years following the combined liver-islet transplant.
Of the 215 adult islet allografts performed in type 1 diabetic patients at 27 institutions between 1990 and 1996, more than 60% of the cases were transplanted at six institutions. Post-transplant positive C-peptide levels in pre-transplant C-peptide negative (plasma C-peptide <0.2 ng/mL) recipients who remain insulin-dependent following transplantation define partially successful islet grafts. Of the 170 type 1 diabetic patients without residual C-peptide secretion pre-transplant who received islet allografts between 1990 and 1996, 30% showed plasma C-peptide levels <0.5 ng/mL at one year post-transplant. About 55% of the recipients had lost graft function within the first month post-transplant. However, the Miami group reported functioning islet grafts over 6 years after islet allotransplantation in two type 1 diabetic recipients. Continued C-peptide secretion is now maintained over 8 years in these patients, and has been associated with long-term normalization or near-normalization of HbA1c levels in the absence of severe episodes of hypoglycemia.
Insulin independence for more than one week was documented in 30 of the 215 recipients transplanted between 1990 and 1996. 13 patients remained insulin independent for more than one year and the recipient with the longest (over 5 years) insulin-independent follow-up was transplanted at Washington University.
Recently, the University of Giessen, Germany, reported that in 12 out of 12 consecutive single donor islet allograft recipients graft failure was prevented during the first 3 months, and 9 patients maintained islet allograft function for more than 12 months (1-year fasting C-peptide 1.8 +/- 0.3 ng/ml). Graft survival was associated with improved metabolic control (HbA1c 6.7 +/- 0.4 vs. 8.1 +/-0.6 % pre-transplant), a lowered incidence of severe hypoglycemia (0.2 +/- 0.2 episodes/patient and year vs. 1.8 +/- 0.5 pre-transplant), and a reduced insulin dosage (7.7 +/- 2.9 U/day vs 41.5 +/- 3.2). (These comments are from a recent review that I wrote with Dr. Bernhard Hering in Current Opinion in Organ Transplantation).
It is still too early to predict when the procedure will be available for your son. Right now there are trials in progress and other planned to test new strategies that will potentially eliminate the need for life-long treatment of the recipients of islet cell transplants with anti rejection drugs. We will not be able to offer islet transplants to children until we can prove that they can be performed without the anti-rejection drugs that are well known to be dangerous, especially for children.
Original posting 22 Mar 1999
Posted to Research: Cure
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