Small Intestines Exposed to Radiation Less Likely to Reject, Reports University of Pittsburgh Transplant Surgeon at Transplant 2001
CHICAGO, May 15, 2001 — The majority of small intestine transplant recipients experience at least one episode of rejection within the first month of transplantation. But in a group of patients whose donor organs were exposed to radiation just prior to transplantation, the incidence was practically zero. Rejection was observed in only one patient of 13 in the study, reported a surgeon from the University of Pittsburgh Thomas E. Starzl Transplantation Institute at Transplant 2001, the joint meeting of the American Society of Transplantation and the American Society of Transplant Surgeons.
"The verdict is not yet in -- more patients need to be studied. But we are really excited about these results. This novel strategy represents a very promising approach that could significantly improve the outcomes for intestinal transplantation," said Kareem Abu-Elmagd, M.D., Ph.D., F.A.C.S., associate professor of surgery and director of the Intestinal Rehabilitation and Transplant Center at the University of Pittsburgh's Starzl Institute.
The protocol involves not only the irradiation of the intestines prior to transplantation, but also donor bone marrow augmentation. While transplant surgery is just getting underway, the donor intestine is exposed for a few minutes to a single low dose of radiation. Surgeons then transplant the organ into the patient and soon thereafter deliver donor bone marrow infusions through a major vein.
Typically, 85 percent of patients receiving intestinal transplants - either alone, with the liver or as a multivisceral graft -- experience at least one episode of rejection within the first 30 days of transplantation. A rejection requires surgeons to administer even more powerful anti-rejection drugs, but at a price to patients. With their immune systems suppressed to protect the transplanted organs from rejecting, patients become more susceptible to infections. The bowel is laden with various microorganisms that, if unchecked, can grow, causing serious systemic infections.
"Even the better drugs have not dramatically improved our ability to prevent and manage rejection and infection, so we set out to develop this alternative strategy involving irradiation and donor bone marrow augmentation," explained Dr. Abu-Elmagd.
The small intestine is full of lymphoid tissue, which is rich in mature immune cells. When a donor intestine is transplanted, these donor immune cells are in such large numbers that they can either aggravate the recipient immune system to attack and reject the intestine or these donor cells can themselves attack the recipient's organs and cause serious damage or even death.
The radiation treatment developed by the University of Pittsburgh team aims to kill enough of these donor immune system cells so that the donor organ is less likely to serve as a target for the recipient's cells. The purpose of the donor bone marrow infusion, which contains immature immune cells, is to enhance a condition called chimerism, whereby certain types of donor and recipient cells learn to coexist peacefully. Chimerism is believed to influence the long-term survival of the transplanted organ.
Of the 13 study patients, nine received small bowel alone, one a liver/intestine transplant, and three, multivisceral transplants involving various combinations of the liver, small bowel, duodenum, pancreas and stomach. Only one patient, a recipient of an isolated small bowel, had rejection. That patient eventually died from complications of the anti-rejection treatment. The others have had not one episode of rejection since their transplants, one for more than one year. All patients are doing well and enjoying normal diets.
Three of five patients in a control group -- patients who received unconditioned small intestinal grafts and no donor bone marrow -- each had at least one serious episode of rejection.
Surgeons at the University of Pittsburgh have performed more than 170 intestine transplants since May 1990, the largest experience of any center in the world. For most of these patients, intestinal failure was caused by short gut syndrome. In adults, this loss of intestine was often due to Crohn's disease, clots, or trauma; for children, short gut syndrome might have been caused by a volvulus -- a twisting of the bowel -- or various congenital conditions. Prior to transplantation, patients are unable to eat solid foods and require intravenous nutrition feedings. In the long term, these feedings can cause liver failure and other life-threatening complications.
At the University of Pittsburgh, actuarial patient survival at one year is 75 percent. Survival among those transplanted within the last five years is 64 percent; and 10-year survival is 42 percent. A patient transplanted nearly 11 years ago is the world’s longest surviving liver-intestine recipient.
The University of Pittsburgh, which successfully petitioned the Health Care Finance Administration to pay for intestinal transplants, is one of three centers approved by Medicare to perform intestine transplants.