by Alicia Chang, 24 January 2008
LOS ANGELES (AP) — 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 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.
