Sep. 6, 2000 Challenged by higher rates of rejection than seen with other types of transplants, researchers at the University of Pittsburgh have devised a strategy that has resulted in not one episode of rejection among its first group of intestinal transplant recipients enrolled in a new study. Exposing the donor organ to radiation outside the recipient's body and just prior to transplantation, plus giving the patient donor bone marrow, appears to effectively stave off immune system attack within the first months following transplantation, the team reported today at the XVIII International Congress of the Transplantation Society.
Kareem Abu-Elmagd, M.D., associate professor of surgery and director of intestinal transplantation at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute, cautions that more patients must undergo the treatment and longer follow-up is required in order to determine if the method has long-term benefits.
"Nonetheless, such findings are significant because, despite improvements in survival rates for intestinal transplants, frequent and difficult-to-treat rejection have continued to defy surgeons. Only within the past 10 years, primarily due to the advent of the anti-rejection drug tacrolimus, has intestinal transplantation been clinically feasible. But because the intestines are laden with immune system cells that serve as a prime target for recipient immune system attack, cocktails of drugs have been only so effective," said Dr. Abu-Elmagd.
Dr. Abu-Elmagd reported on the results of five patients at high risk for rejection who received irradiated intestines as part of an isolated small bowel, liver and small bowel or multivisceral transplant. While transplant surgery was just getting underway, the donor intestine was exposed for a few minutes to a single low dose of radiation. Surgeons then transplanted the organ as well as delivered donor bone marrow to the patient. None of the patients have had evidence of rejection for up to four months.
In contrast, two study control patients, who received untreated grafts and no bone marrow, experienced the typical course of rejection within the first few weeks after transplantation. While these patients' episodes were successfully treated, rejection for intestinal transplant patients can often be quite severe. According to the Pittsburgh experience -- the most extensive of any center -- about 84 percent experience at least one episode of rejection. The researchers' protocol includes both the irradiation technique and donor bone marrow infusion, which contains immune system stem cells, because results of their animal studies showed that the combination method reduces the incidence of chronic rejection.
The five patients who participated in the study are among 143 patients who have received 151 intestinal transplants at the University of Pittsburgh Medical Center (UPMC) since May 1990. Fifty-seven received isolated small bowel, 72 liver/small bowel and 22 received multivisceral transplants. The majority (81 percent) of the patients at UPMC required intestinal transplants because of short-gut syndrome, the loss of more than 70 percent of the intestine due to trauma, surgery or disease. For adults, short gut syndrome may be caused by trauma or Crohn's disease; for children, it may be a volvulus -- a twisting of the intestines, or congenital conditions.
The overall patient survival at UPMC at one year is 72 percent; the cumulative five-year survival is 52 percent. Thirty patients are beyond three-year and 25 patients are well beyond five-year milestones. Survival rates have improved to the current rates due to better management of immunosuppression, refined donor and recipient selection criteria and modification of the surgical procedure, reported Dr. Abu-Elmagd. According to Pittsburgh and International Registry data, risk factors affecting survival are frequency of rejection, a cold ischemia time-- when the donor organ is without blood supply--of greater than nine hours, and center volume (centers performing fewer than 10 transplants have worse outcomes).
Intestinal transplantation allows patients to be free of the need of intravenous nutrition and its associated risks of complications, including the potential for liver failure. The majority of the patients in Pittsburgh (95 percent) are now able to eat a normal diet. And according to quality of life studies conducted at the University of Pittsburgh, patients experience other significant improvements in their physical and psychological well-being as well.
With such improved survival rates and quality of life, as well as the demonstrated cost benefits of transplantation compared to long-term use of total parenteral nutrition, UPMC surgeons are appealing to the U.S. Health Care Financing Administration to require that the federal Medicare program cover the costs of the procedure. A decision is expected next month.
The University of Pittsburgh's transplant programs are world-renowned for their cutting-edge research contributions and sheer volume of experience. Since 1981, with the arrival of transplant pioneer Thomas E. Starzl, M.D., Ph.D., more than 10,000 organ transplants have been performed at the University of Pittsburgh. In addition to having among the most active liver, intestine, kidney, pancreas, heart and lung transplant programs, UPMC also has established the uniquely successful Istituto Mediterraneo per I Trapianti e Terapie ad Alta Specializzazione (ISMETT). ISMETT is a partnership between the Italian government, Civico and Cervello hospitals in Palermo and UPMC. Since last year, more than 18 livers and 13 living-related kidney transplants have been performed there.
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