Doctors experiment in weaning transplant patients off anti-rejection drugs

WASHINGTON (AP) _ Lynette Fralick in January received an intestine transplant, the organ most prone to being rejected when it's put into a new body. Yet in a daring experiment, the New York woman has

Monday, September 2nd 2002, 12:00 am

By: News On 6

WASHINGTON (AP) _ Lynette Fralick in January received an intestine transplant, the organ most prone to being rejected when it's put into a new body. Yet in a daring experiment, the New York woman has been weaned down to a mere three anti-rejection pills a week, not the usual handfuls that transplant recipients swallow.

Powerful medications keep transplant patients' immune systems from attacking and destroying their new organs, but they also can cause debilitating, even deadly, side effects.

Now, in a series of experiments spanning the globe, scientists are trying different methods to wean several hundred transplant recipients off anti-rejection drugs.

They're nerve-racking studies: The patients could lose their new organs, even their lives, in the still elusive quest to go drug-free. Indeed, some patients undergoing weaning have had to quickly resume the pills when rejection started to occur. Transplant surgeons insist that organ recipients should not try quitting on their own.

Yet a small but growing number of successes has scientists edging closer to understanding what makes some bodies able to tolerate a stranger's cells _ an understanding indispensable to determining one day which patients might be able to safely dump the pills.

``The question is how low can you go'' with anti-rejection pills, explains Dr. Samuel Strober of Stanford University. ``Can you go to zero, and if you go to zero, how long?''

Even if patients can't quit completely, ``everybody is of the same mind that the price that one pays of lifelong immunosuppression is higher than we'd like right now, and you'd like to reduce it,'' he says.

``We are on the right track,'' agrees Dr. Kareem Abu-Elmagd of the University of Pittsburgh, which is attempting to wean Fralick and more than 100 other recipients of new livers, kidneys or intestines.

The drug-free quest was spurred by Pittsburgh transplant pioneer Dr. Thomas Starzl's discovery in 1990 of seven people given kidney transplants 40 years earlier, who had stopped their anti-rejection medicine later in life, yet miraculously survived. They had a trait called chimerism _ some of the donor's immune cells rode in during the transplant and spread until donor and recipient cells peacefully coexisted in their bodies.

But there's no way, yet, to know in advance who would be so lucky. So doctors are hunting ways to force chimerism. Among the attempts reported at a major transplant meeting last week:

_In the Pittsburgh experiment, scientists administer one pre-transplant dose of a medicine that kills certain immune cells. Then, after 90 days of lower-than-usual doses of one anti-rejection drug, tacrolimus, patients with no signs of rejection are slowly weaned off. Of 120 now being weaned, several dozen are down to one, two or three pills a week; the goal is eventual stoppage.

That directly contradicts today's standard practice of major immunosuppression immediately following surgery. The Pittsburgh theory is that allowing an early but mild immune reaction permits attack cells that initially targeted the new organ to lose interest and die off.

``I'm feeling great,'' says Fralick, 40, of Medina, N.Y. But she wants to stay at just three pills a week for a while before the scarier step of further weaning. ``I don't want to get to the point where I may go into rejection,'' she said.

_Other researchers suspect infusions of tissue or stem cells from donors before transplanting the actual organ may help mediate rejection. Scientists at the Institute of Kidney Diseases in Ahmedabad, India, infused donor kidney tissue into the recipient's thymus _ where developing immune cells are directed to their target _ 15 days before kidney transplant. Some 26 kidney recipients have been off all anti-rejection drugs for three months.

_Stanford researchers implanted kidneys into four people, then gave them radiation to kill certain immune cells and then infused immune-spurring stem cells taken from their kidney donor. For a few months, all showed signs of chimerism as the donor and recipient immune cells mixed _ and two were able to stop anti-rejection pills for five months before an early warning sign of rejection sent them back on low doses. A third is weaning now; one had early rejection that prohibited weaning.

_Stem cell infusions alone aren't the answer, say University of Miami doctors, who have 19 liver recipients off all anti-rejection drugs, 10 for more than a year. Some of these patients received no pretreatment.

Modena Bailey, 77, of Davie, Fla., doesn't know why she's one of the lucky ones: ``I just say, 'thank God I'm off all those pills','' she said.