Experimental Post-Transplant Protocol May Eliminate Need for Immunosuppressants

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One of the biggest complications associated with organ transplants is the need for lifelong use of immunosuppressants to prevent rejection, which typically cause a number of serious side effects.

But a recently developed post-kidney transplant regimen developed by doctors at the Stanford University School of Medicine could make it possible for patients to live without the need for immunosuppressive drugs.

Eight of 12 patients given the new post-transplant protocol, which consisted of radiation and donor stem cells, were able to be weaned off immunosuppressants after about six months and were able to stay off them for at least one year and in some cases, three years.

"The majority of patients were able to discontinue antirejection medications, and all patients had excellent graft function at the last observation point," the authors wrote.

In a short letter published in the New England Journal of Medicine, the doctors described the protocol, called "induced immune tolerance" in the kidney transplant patients.

After their transplants, the patients received small doses of radiation as well as stem cells from their donors with the hope that these donor cells would mix with their own cells and be recognized by the body as their own.

So far,the patients have done well.

"Nobody has had any evidence of rejection, and the patients have been observed for at least a year and as long as three-and-a-half years and things have remained quiet," said Dr. Samuel Strober, the protocol's inventor and a professor of medicine at Stanford. For decades, Strober and other groups of surgeons have been researching how to get the immune system to tolerate "non-self" material as well as it does the body's own.

Immunosuppressants: Serious Side Effects

Transplant surgeons not involved in the Stanford research say the new therapy is very promising since a lifetime of anti-rejection medicines can involve serious complications.

"It would be great if we could do something up front and just stop the immunosuppressants," said Dr. Jonathan Bromberg, chief of the division of transplantation at the University of Maryland Medical Center in Baltimore. "They can hurt the kidneys, can cause weight gain, high blood pressure, diabetes, make people more susceptible to infections and because they can cause high blood pressure and diabetes, they can increase susceptibility to cardiovascular disease."

Some transplant patients can live without immunosuppressive drugs, but it's not yet clear why.

"Some people have their own tolerance to the transplanted organ that develops, but we're not sure why that develops in some people and not others," said Dr. Michael Porayko, medical director of liver transplantation at Vanderbilt University Medical Center in Nashville.

While being able to avoid the harmful effects of immunosuppressants is a huge benefit of this new regimen, there are also potential drawbacks.

"The downside is you have to irradiate people. You could have problems later on because radiation in its own right can cause problems," said Dr. Lewis Teperman, chief of transplant surgery at NYU Langone Medical Center in New York.

Strober and his colleagues tried the new protocol in patients whose donors were perfectly matched.

"These work very well and have a very small chance of rejection," said Bromberg.

"Exciting" Development, But Will it Last?

"It's always exciting when a protocol like this comes out, but we need to look at it with larger numbers of people," said Teperman.

"It's also not clear if it will work with other solid organs, like the liver or the lungs," said Porayko.

Dr. George Burke, professor and director of Lillian Jean Kaplan Renal Transplantation Center at the University of Miami's Miller School of Medicine, said he's cautiously optimistic about the research. He believes future studies should address, among other things, the role of other types of immune cells called memory T cells.

He also expressed concern that news of this research could lead transplant patients to stop taking their immunosuppressants.

"If a patient who is doing well stops immunosuppressants, it's almost a guarantee that they will experience rejection and lose the transplant," he said.

Strober said the university is currently enrolling transplant recipients who are only partially matched with a donor to test how well the post-transplant regimen works in these patients.

If tolerance persists in kidney transplant patients over the long term, Strober said it would be an incredible medical advance.

"Patients who need transplants have had kidney failure, and the transplant procedure is a way to treat organ failure. If we can restore them to normal kidney function without drugs and they continue to do well, we can say in some way these people are cured of organ failure."

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