Major breakthrough for organ recipients

LOS ANGELES -- In what's being called a major advance in organ transplants, doctors say they have developed a technique that could free many patients from having to take anti-rejection drugs for the rest of their lives.

The treatment involved weakening the patient's immune system, then giving the recipient bone marrow from the person who donated the organ. In one experiment, four of five kidney recipients were off immune-suppressing medicines up to five years later.

"There's reason to hope these patients will be off drugs for the rest of their lives," said Dr. David Sachs of Massachusetts General Hospital in Boston, who led the research published in Thursday's New England Journal of Medicine.

Since the world's first transplant more than 50 years ago, scientists have searched for ways to trick the body to accept a foreign organ as its own. Immune-suppressing drugs that prevent organ rejection came into wide use in the 1980s. But they raise the risk of cancer, kidney failure and other problems. Some have unpleasant side effects such as excessive hair growth, bloating and tremors.

Eliminating the need for anti-rejection drugs is "a huge advance," said Dr. Suzanne Ildstad, a University of Louisville immunology specialist who had no role in the work.

"It still needs some fine-tuning so that everyone who gets treated gets the same consistent outcome. ... It's not the holy grail of tolerance yet," she cautioned.

The results do not mean that it is safe for current transplant patients to go off their medicines. Doing so could lead to organ rejection and death, doctors warn. And Sachs said the treatment will not solve the country's organ shortage.

In the 1990s, Sachs showed the treatment could work in a kidney recipient who was a good genetic match. The woman, who had an organ and marrow transplant in 1998, has not needed anti-rejection drugs for a decade.

The new study involved five people who got kidneys from parents or siblings who had slightly different tissue types from the patients. Since many kidney transplants are similarly mismatched, there is hope more people might one day be spared immune-suppressing drugs.

Doctors have experimented with giving marrow before, during or after organ transplants, while also tinkering with patients' immune systems to prime them to accept the new organs.

Sachs' treatment involved weakening each kidney patient's immune system with intravenous drugs several days before the transplant. After the transplant, the patient got an infusion of marrow from the donor to create a new immune system.

The stem cells from the marrow reprogram the body by allowing new immune cells to grow that don't try to attack the donated organ.

The patients took anti-rejection drugs but were weaned several months later.

Four of the five patients developed a hybrid immune system -- where recipient and donor cells live together in the body -- for a short time. They were able to stop the anti-rejection drugs and had healthy kidney function two to five years later.

In the one case that failed, the patient had a second kidney transplant and has been on medications since.

The study was financed by the Immune Tolerance Network, an international consortium of federal and advocacy groups.

At Fred Hutchinson Cancer Research Center in Seattle, the same type of stem cell and organ transplant was successfully done about five years ago, said Dr. Rainer Storb, head of the center's transplantation biology program. Four cancer patients who were on dialysis were given stem cell transplants, then two years later when their cancers were gone, underwent kidney transplants from the same donors and didn't need anti-rejection medication, said Storb.

The transplants weren't written up in any paper, he said, because the principle isn't new and was first documented in a mouse by Seattle researchers in 1956.

What is new is that unlike the Fred Hutchinson patients, who had perfectly matched donors, patients in the New England Journal of Medicine studies weren't fully matched -- putting the concept one step closer to widespread use, Storb said.

He said researchers at the Hutch are also studying ways to achieve this.