MONDAY, Aug. 26, 2002 (HealthDayNews) -- A transplant approach pioneered 40 years ago has been resurrected as a way to preserve organ grafts with fewer or potentially no immunity-blocking drugs.
The technique involves wiping out key immune cells before transplant surgery, followed by doses of a single immune-suppressing medication. Many patients can slowly be weaned off the drug, and a few have even been able to drop the therapy completely without suffering rejections of the graft, the researchers say.
"It's exciting, in that many centers are seeing similar results with similar strategies," says Dr. Allan Kirk, a transplant expert at the National Institute of Diabetes and Digestive and Kidney Diseases. "That suggests what people are seeing is real."
Kirk is among a handful of researchers presenting their results with this new-old approach today at the International Congress of The Transplantation Society in Miami. Eventually, he says, as many as 80 percent of transplant patients might be able to avoid rejection on a single immune-suppressing agent. And many could get by on greatly reduced doses of the compounds.
Because these drugs are highly toxic and highly expensive -- it's common for patients to spend $20,000 a year on the therapy -- anything that would reduce the burden of immune-suppressing treatment would be a boon, Kirk says.
"I think there is a need to do it, and it might work," says Dr. Stuart Kanechtle, a University of Wisconsin surgeon. "But we need to figure out how to do it long-term."
The method involves muzzling the activity of the T-cells that marshal the response to an invasion of foreign tissue. Because trauma, including surgery, is frequently a way germs and viruses enter the body, it's not surprising T-cells are on high alert after an operation. While this is good for fighting infection, it's bad for helping the body make peace with a donor organ.
In the early 1960s, scientists reasoned they could clamp down on the T-cell surge after transplant surgery by blocking them before the procedure. They had the right idea, Kirk says, but primitive tools.
Recently, however, some surgeons have revived interest in the practice of T-cell depletion.
In one of the studies to be presented, researchers at the University of Pittsburgh showed that 12 of 22 small-bowel recipients who underwent T-cell depletion are being weaned off the immune-quashing drug tacrolimus.
Although 10 haven't fared as well, and three of the 12 suffered rejections after weaning began, Dr. John Fung, director of transplantation surgery at Pitt, says even that success rate among small-intestine patients is a major victory, because these people are particularly prone to rejections.
Fung is presenting an overview of the Pittsburgh protocol, which is nearing its one-year anniversary. Roughly 80 of 250 patients, including 20 liver recipients, 40 kidney recipients and the 22 bowel recipients, have begun weaning off their immune-suppressing drugs.
The protocol involves killing T-cells with a substance called rabbit anti-thymocyte globulin. If after 90 days the patients show no signs of rejection, the doses of immune-suppressing drugs they take are gradually scaled back.
None is completely off medication, Fung adds. However, some of the most advanced patients are now taking a weekly dose of immune-blocking therapy, compared with the routine of two or three drugs twice a day or more required by conventional treatment.
"The weaning process is critical. You can't just stop the drugs entirely without increasing your risk of rejection," he says.
Kanechtle and his colleagues are reporting the results of 29 kidney transplant recipients who had their T-cells wiped out with a drug called Campath-1H. They are now receiving "maintenance" doses of the immune-blocking compound rapamycin, or sirolimus, and are "doing very well," he says. The Wisconsin group plans to start weaning several of these patients off rapamycin to see if they'll continue to keep their new kidneys.
Complete freedom from immune suppression is the promised land for transplant patients and surgeons alike. A small number of people appear to have reached this happy state, says Kanechtle, who has been following "a couple" of these patients at his hospital in Wisconsin.
However, why these patients do so well, while others who are weaned off the graft-preserving drugs ultimately suffer rejections, remains a mystery, he says.
"They're very interesting and important patients, but these are rare exceptions in the big picture," he says. "I think we need to learn as much as we can from them, and try to learn why they're tolerant."
What To Do
For more on organ transplants, visit the United Network for Organ Sharing or the American Liver Foundation.
