Transplants Transformation?

I. Lewis "Scooter" Libby, former Chief of Staff to Vice President Dick Cheney, leaves the federal court house Wednesday, Feb. 21, 2007 in Washington. Jury deliberations began in the case against Libby who is accused of lying under oath during an investigation into CIA employee Valerie Plame's blown cover.
All Janet McCourt wanted that day in 1998 was a new kidney to help her live long enough to see her first grandchild. She ended up fibbing her way into medical history.

Today, at 59, the suburban Boston resident is a grandmother of three. And scientists have an encouraging success story for an experimental technique that could one day make life for transplant patients a lot easier.

For virtually all the three years since McCourt got the kidney, she hasn't had to take drugs to keep her body from rejecting the organ. While there are unusual cases of other transplant patients getting by after they stopped taking such drugs, the reason is a mystery, and it's not clear how to take advantage of their success for future patients.

McCourt, in contrast, is the first person to go through a procedure that combined her immune system cells with those of an organ donor to make her body accept an organ naturally. A second kidney patient followed a year ago.

Their continuing health "gives us the courage and enthusiasm to suggest this is a possibility" for freeing transplant patients from a lifetime of taking anti-rejection drugs, said immunologist Dr. David Sachs of Massachusetts General Hospital, who is studying the procedure.

At the moment, of course, anti-rejection drugs remain a breakthrough that makes modern-day transplant successes possible. Transplant patients need the medications because their immune systems, designed to fight germs, recognize tissue from other people as foreign and attack them. The drugs interfere with that.

But these drugs bring their own complications, notes John Butorac, executive director of the American Transplant Association.

They cost about $10,000 a year, on average. And they can cause hair to grow all over the body - "not so great if you're a teen-age girl" - along with overgrowth of gums, high blood pressure, high cholesterol and increased risks of cataracts, glaucoma and cancer. And over time, they can make kidneys fail, he said.

But "in the end," he said, "it still beats the alternative."

McCourt, for one, was looking for a standard kidney transplant the day she told her fib in 1998. She had been on dialysis a little over a year, starting just after she was diagnosed with a bone marrow cancer called multiple myeloma and given perhaps six months to a year to live. The cancer had made her kidneys fail, and it also kept doctors from giving her a new kidney.

Dialysis sessions were especially hard on her. She tended to faint and vomit. It took a day to recover, and with three sessions a week, McCourt could count on only about one day every week when she felt reasonably normal. As a former businesswoman, she felt her active life had been shut down.

Her cancer appeared to be in remission after McCourt, inspired by the prospect of becoming a grandmother, plunged into a bundle of nontraditional therapies. But doctors still wouldn't give her a kidney.

"I could have lived with the cancer (for) maybe couple of years," McCourt said. "But I could not take two more years of the dialysis."

So she took matters into her own hands. On a day when she knew a certain doctor would be on vacation, she told the head nurse at her dialysis center that the missing doctor wanted her to meet with a transplant coordinator at Mass General.

The coordinator turned her down because of the cancer, but McCourt figured she had a foot in the door. She pleaded her case again, saying she "would do anything to have a transplant," and that she was planning to take herself off dialysis."

With the coordinator's help, McCourt met some Mass General researchers who had been looking for somebody just like her, with the combination of multiple myeloma and failed kidneys.

Their kidney transplant procedure involved transplanting bone marrow at the same time, and standard marrow transplants had cured multiple myeloma, Sachs said. So it made sense to try their experiments in people who could benefit from a marrow transplant anyway.

So on Sept. 22, 1998, doctors led by Dr. A. Benedict Cosimi transplanted in McCourt a kidney donated by her younger sister. Then a bone marrow transplant team headed by Dr. Thomas Spitzer fed about two pints of her sister's marrow into a vein through a tube in McCourt's chest. The marrow cells found their way to her bones, where they took up residence along with McCourt's own.

Why does this help?

Basically, "you retrain the immune system," Sachs said. The goal is to expand its idea of what normal tissue in the body looks like, so that a donated organ appears to be an old friend.

The immune system gets its idea of what "normal" looks like from certain cells in the bone marrow. So, in McCourt's case, the marrow transplant let her immune system take direction from both her own marrow and her sister's. That paved the way for her body to accept her sister's kidney.

There's more to the treatment than the specially modified marrow transplant. Organ recipients must take an anti-rejection drug for a while, no longer than about two months. And they are treated with radiation and a drug to wipe out many of the mature T cells that were already programmed to attack anything foreign. That doesn't eliminate all of them, but somehow the remainder haven't seemed to cause trouble for McCourt or the second kidney transplant patient, said Dr. Megan Sykes, another of the Mass General researchers.

Maybe the new kidney itself retrains those lingering T cells, Sykes said.

In any case, the results with the two women so far are "phenomenal," said Steve Rose, director of the office of clinical applications at the National Institute of Allergy and Infectious Diseases.

Rose is in charge of giving grants for a program that seeks ways to make organ recipients' immune systems accept new organs. While scientists are exploring a number of strategies, the approach of Sachs and Sykes appears to be one of the most promising, he said.

Eventually, the tw researchers say, the technique might be useful for a wide range of organ transplants, including livers, hearts and pancreatic islets used to treat diabetes. Farther into the future, it might let people easily accept organs from pigs, easing the shortage of human donated organs.

But don't look for this technique, called mixed chimerism, to be used at your local transplant center any time soon.

For one thing, McCourt and the later patient are only two cases - encouraging, but hardly solid scientific evidence. Sykes and Cosimi are leading a larger study, to be done at hospitals in New York and Atlanta as well as Mass General, to try the technique in more patients with multiple myeloma and resulting kidney failure.

Cosimi and Sachs, the immunologist, meanwhile, are starting a study of people who want a kidney transplant but have no other need for a marrow transplant. A big question will be whether the risks and side effects of the marrow procedure outweigh those of taking anti-rejection drugs for life.

Another hurdle to widespread use is that with the current procedure, prospective kidney recipients have to go through about six days of treatment before the transplant. There's time for that if the donor is alive, but donated hearts and livers come from cadavers and must be used right away.

Sykes said animal studies give her hope that human recipients could eventually get an effective treatment right before the transplant.

In the meantime, McCourt said she's had no sign of kidney rejection, although that risk is never far from her mind.

"The minute you get sick, the minute you get even a tinge of pain in your kidney, you say, `This is it, I've been too lucky too long,"' McCourt said. "It's constant, it never goes away."

But in fact, "I'm extremely healthy." The cancer, she says, is gone.

Last spring McCourt dyed her hair red - "I needed a little sparkle in my life" - and bought a bike. These days she spends lots of time outdoors for her photography classes at the University of Massachusetts in Boston, where she is majoring in art.

The first two years after the transplant she was nagged by colds and flu. "Whatever was out there, I got," she said.

But since then, she has largely avoided getting sick. This fall, while her fellow students were catching colds all around her, she stayed healthy. In early November, when McCourt finally came down with some sort of a bug, it lasted only three days.

"I think my immune system is starting to build up again," she said. "I guess I (was) due for a bout of something."

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