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New Therapies Could Change Organ Transplants
Date:1/23/2008

Three reports show some patients went five years without anti-rejection drugs

WEDNESDAY, Jan. 23 (HealthDay News) -- Therapies that allow organ transplant recipients to stop taking powerful immunosuppressive drugs are starting to come to fruition.

"The next stage in the development of the transplant field is to completely withdraw those drugs and be able to have the lifesaving benefit of the transplant without the costs of the lifelong immunosuppressive drugs," said Dr. Samuel Strober, senior author of a paper describing one of these therapies and a professor of medicine at Stanford University School of Medicine.

The procedures, detailed in three reports in the Jan. 24 issue of the New England Journal of Medicine, won't expand the pool of donor organs, but they could greatly improve the outlook for those who receive organ transplants.

"We hope it will make a major difference in how transplants are done," said Dr. David H. Sachs, senior author of one of the studies and director of the Transplantation Biology Research Center at Massachusetts General Hospital in Boston. "Patients don't have to take immunosuppressor drugs all their lives, which is one of the major problems with transplants. The drugs are wonderful, but they have complications."

Those complications can include cancer and, ironically, kidney damage.

"Doctors did a great job about developing the use of transplants for people who had [organ] failure. The problem is that all people who get transplants have to go on lifelong immunosuppressor drugs, and those have lots of side effects, especially when used for very long periods of time. They also have substantial financial costs," Strober said. "It's a lot better to get these patients off the drugs."

Some 5 percent to 7 percent of organ transplant fail every year even if the individuals take their drugs religiously.

Both Sachs' and Strober's research involved "tricking" the immune system into thinking the organ had come from the recipient. Both procedures also involved transplanting donor stem cells into the recipient.

"The ability to achieve tolerance in what's called stable chimerism [when donor cells are present in the recipient] in patients has been postulated since the 1960s," said Dr. Roy Smythe, chairman of surgery at Texas A&M Health Science Center School of Medicine. "It's really been a 'gee whiz' thing for the last 30 years. . . This is proof of principle in human beings, which is a big deal."

But, Smythe noted, forcing tolerance in transplant patients poses a fair bit of danger. "It's going to be tough at first, but the likelihood is, in the next 10 years, we will find less injurious and dangerous ways to prepare people for tolerance, so eventually it will be a safe thing to do. There's a long road to hoe yet, but it's going to happen. It's very exciting."

In the Sachs study, four of five patients who had HLA-mismatched kidney transplants were able to stop taking immunosuppressive drugs nine to 14 months after the transplant. Kidney function has stayed stable for up to 5.3 years since the transplantation.

HLA refers to human leukocyte antigens, which is one of the primary ways donors and recipients are matched. HLAs, found on the surface of virtually all cells, help tell the difference between normal body tissue and foreign substances.

All patients first underwent a procedure to partially destroy their bone marrow and reduce the level of T-cells (the part of the immune system most responsible for organ rejection). The bone marrow eventually regenerated and produced new immune cells which accepted the new organ.

The procedure had already been successfully performed on matched transplants.

Strober and his colleagues altered the immune system of a man who had received a closely matched kidney from his brother. The man has lived without immunosuppressant drugs for two years.

Unfortunately, six other patients who received the same treatment have not been able to give up their immunosuppressive drugs. Their kidneys were not as well-matched, however.

A third study, from Australian researchers, involved a 9-year-old girl who had received an HLA-mismatched liver from a deceased male donor and who was also able to come off immunosuppressive medications.

Essentially her body did naturally what the other two studies had to induce, Smythe said. She developed a viral infection, which dropped the number of her own white blood cell counts and allowed donor white blood cells that were in her body to take over. Being a child also helped. "My guess is that this was a large graft in a small person," Smythe said.

These advances may one day indirectly alleviate the biggest problem facing the transplant field: a shortage of donors.

"We hope this will be even more important when applied to xenografts [grafting tissue from one species, such as a pig, to another, such as a human], which will increase donors," Sachs said. "We think the pig is going to be the answer to that. We have been breeding special pigs for that purpose."

More information

Learn more about organ transplantation at the United Network for Organ Sharing.



SOURCES: David H. Sachs, M.D., director, Transplantation Biology Research Center, Massachusetts General Hospital, Boston; Samuel Strober, M.D., professor, medicine, Stanford University School of Medicine, Palo Alto, Calif.; Roy Smythe, M.D., chairman, department of surgery, Texas A&M Health Science Center School of Medicine, and Scott &White, Temple, Texas; Jan. 24, 2008, New England Journal of Medicine


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