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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 the January 24 edition of 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 many other problems. And they 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 even 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.
The breakthrough has changed the life of a Los Angeles man who was one of Sachs’ patients.
Derek Besenfelder was born with a genetic kidney disease. After a year on dialysis, he decided to enroll in the experiment and received a kidney and marrow transplant from his mother in 2005. He took anti-rejection pills for eight months, but then was weaned from them. He has been drug-free for two years.
“I wanted to be off the drugs as soon as possible. I had this huge bloated face and didn’t feel comfortable going out in public,” said Besenfelder, 28, who works as a communications director for a Beverly Hills plastic surgeon.
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 taking 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.
Some researchers such as Ildstad believe the “home run” breakthrough will come when more people respond to the treatment and keep the mixed immune system permanently.
Transplant pioneer Dr. Thomas Starzl of the University of Pittsburgh said donor cells appeared to persist in the bodies of the successful transplant recipients even if those cells were not readily detected.
As promising as the treatment is, Sachs said it won’t solve the country’s organ shortage problem. Nearly 98,000 people are on the waiting list, according to the United Network for Organ Sharing.
The study was funded by the Immune Tolerance Network, an international consortium of federal and advocacy groups. Sachs plans a follow-up study involving 15 to 20 patients at Massachusetts General and other hospitals.
In the same issue of the New England Journal, Stanford University doctors reported successfully inducing tolerance to a donor organ in a man who was born with one kidney.
Larry Kowalski, now 50, received a matching kidney and marrow from his brother in 2005 and was weaned off drugs six months later. He has been off medications for two years.
Unlike the Massachusetts General cases, doctors said Kowalski has maintained an immune system from his own cells and his brother’s. The research was funded by the National Heart, Lung and Blood Institute.