New islet cell transplant procedure uses only one donor pancreas.
Changes in the recipients" immunosuppressive therapy regimen and the way the donor pancreases are stored and processed before transplantation have probably made the single-donor procedure possible and may make islet cell transplantation available to more people, said Dr. Hering of the University of Minnesota, Minneapolis, and his associates.
"Our results mark a distinct advance in islet transplant efficacy. We not only achieved insulin independence using islets from only one donor pancreas [compared with two or four in the Edmonton trial]; we also achieved superior glycemic control using fewer islets," they said.
The researchers conducted the transplants from 2001 to 2003 in eight women with type 1 diabetes, using islet cells from one donor pancreas for each transplantation. All donors were younger than 50 years. The pancreases were preserved for no more than 8 hours by a two-layer method in which the pancreas is placed between a lower layer containing perfluorochemical and an upper layer containing the University of Wisconsin (UW) organ preservation solution. This method of preservation doubles islet yields and increases the acceptable preservation time to 24 hours, compared with conventional UW storage (JAMA 2005;293:830-5).
The islets were isolated, purified, and cultured for 2 days before transplant. Of 18 donor pancreases, 8 yielded adequate islets for transplantation.
The recipients began induction immunosuppression 2 days before the procedure with rabbit antithymocyte globulin and methylprednisone. On the day of the procedure, they began receiving daclizumab (five doses of 1 mg/kg every 2 weeks) and etanercept (50 mg 1 hour after the procedure, followed by 25 mg on days 3, 7, and 10).
Patients received the islets through transhepatic portal venous catheterization.
Maintenance immunosuppression consisted of sirolimus and reduced-dosed tacrolimus. At 1 month post transplantation, the tacrolimus was gradually replaced with mycophenolate mofetil; tacrolimus was either discontinued or reduced to a trough level of less than 3 ng/mL, depending on sirolimus trough levels. Tacrolimus was continued if target levels of sirolimus (5-15 ng/mL) couldn't be maintained.
There were no procedural complications, other than transient lymphopenia and neutropenia, as expected. All eight recipients became insulin independent, but three did not maintain independence, including two who tested positive for autoantibodies and alloantibodies.
Five patients maintained insulin independence for more than 1 year, and four of those had normal glucose metabolism as measured by oral glucose tolerance testing at 180 days or more post transplantation. None of the five patients tested positive for auto- or alloantibodies. All of them either maintained sirolimus trough levels of more than 9 ng/mL with low tacrolimus trough levels or achieved tacrolimus trough levels of 3-6 ng/mL in the absence of target sirolimus trough levels.
Factors that led to success with only one donor pancreas include the use of etanercept, the investigators suggested. "Etanercept administration is a new addition to our protocol ... and could have been a major factor allowing consistent diabetes reversal with a low islet dose," they said.
MICHELE G. SULLIVAN
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|Author:||Sullivan, Michele G.|
|Publication:||Family Practice News|
|Date:||Mar 15, 2005|
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