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Drug-Free Hope For Transplants

Jennifer Duran knows a bit about how challenging life will be for the French woman who got a face transplant.

After a kidney transplant at age 13, Duran took "20-something pills a day" to keep her body from rejecting her new organ. The drugs' side effects included facial hair — "not a good thing when you're a 13-year-old girl" — and memory problems that linger to this day.

The worst was the warts on one leg and foot, so painful that as a college student she often couldn't walk.

But today Duran, 26, is the picture of hope to many transplant patients. Her first donated kidney was replaced by a second one in 2002, along with a promising experimental treatment. Now she doesn't take any of the anti-rejection drugs the French woman will likely take for life.

"For the first time in my life, I know what healthy is. I'd never known that before," said the Boston area librarian.

Duran is the shining example of a risky approach: Doctors killed off her entire immune system and gave her bone marrow from her organ donor before she got the new kidney. The bone marrow stem cells gave her a new immune system that doesn't try to reject her donated organ.

"I'm very excited. It's still fairly new, but if it continues to work as well as it has so far, I think this could benefit a lot of people," said Dr. David Sachs, an immunologist at Massachusetts General Hospital.

He's tried the experimental technique on four patients and been successful with three, including Duran. One of his successes is a grandmother in her 60s who's been living without anti-rejection drugs for seven years.

But other doctors view the technique as too dangerous to use in all but the most urgent cases.

"Many people wouldn't survive the regimen," said Dr. Hans Sollinger, a professor of surgery and chairman of transplantation at the University of Wisconsin-Madison. "The regular (transplant) surgery is a walk in the park compared to this — it's much too toxic right now."

In Duran's case, however, the new procedure gave her a new life. Duran, whose kidneys began to fail at an early age, is believed to be the only person in the world to undergo both a standard kidney transplant and a second kidney transplant that also included a bone marrow cell injection.

The woman in France who became the first in the world to get a partial face transplant is getting a similar experimental treatment, but details of it are unclear, and Sachs and other doctors are skeptical of it based on what they have read.


The French doctors said they gave their patient injections of bone marrow from the same donor who provided the transplanted facial tissue. But that procedure came days after she had already received the face transplant, and the patient's original immune system wasn't killed off first. The doctors said they hoped that might enable her to take lower doses of anti-rejection drugs.

In Duran's case, the immune system was first destroyed, then the donor's bone marrow was injected at the same time the new organ was implanted.

The human immune system is an army of cells that continuously circulate through the body, always on the lookout for things that don't belong there. After the immune cells are created in the bone marrow, they get programmed, or educated, to know the difference between body cells to be protected and foreign cells to be attacked.

In a transplant, doctors implant a foreign organ. Even though the organ helps the body function, the patient's immune system will recognize it as enemy tissue and try to destroy it.

So doctors have to give transplant patients anti-rejection drugs that interfere with the immune system to protect the new organ. The patient needs these drugs for life.

But the drugs can have harsh side effects, as Duran can attest. In addition to excess body hair and painful warts, patients can be more vulnerable to conditions such as cancer and osteoporosis.

Even though she's only 26, Duran developed cataracts in both eyes. The medicines, she said, "completely compromise your quality of life."

With the new procedure, the patient gets a brand new immune system from the organ donor so that the body doesn't attack the new organ. That means there's no need for anti-rejection drugs.

But this freedom comes at a steep price: All of the patient's immune cells have to be killed off so the donor's bone marrow cells can help replace them with cells that accept the new organ.

"You kind of wipe out the system and start over," said Dr. Hugh Auchincloss, the deputy director of the Immune Tolerance Network, a consortium that's researching new ways to make the immune system accept transplanted tissue.

The grueling procedure involves drug and radiation treatments that leave the patient exhausted, in pain and without an immune system for weeks.

The technique left Duran in a sterile hospital room for several weeks. For the first few days after surgery she had so much pain she could only moan for morphine.

But within a month her strength returned. In two months she was starting a normal life. Two years later she ran a half-marathon and expects to run a full one next month. And, except for a few weeks of mild anti-rejection drugs immediately after her surgery, she's been completely free of them and their side effects ever since.

"Because I've had the surgery both ways, I tell anyone who'll listen how great it is," she said. "I tell them it's a month of suffering for a lifetime of normal."

Sachs is equally pleased with the outcome. He estimates that fewer than 100 patients are enrolled in clinical trials for the new procedure, though, so it might be some time before it becomes commonplace.

Sollinger estimated that the technique has been used successfully at least a dozen times around the world, including in Wisconsin, New York and Germany. He said the science is sound but the process needs to be safer before it can be tried on more patients.

By Dinesh Ramde