- The Washington Times - Tuesday, September 3, 2002

ASSOCIATED PRESS
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.
Transplant patients usually take large doses of powerful medications to keep their immune systems from attacking and destroying the new organs. But the drugs also can cause debilitating, even deadly, side effects.
Now, in a series of closely monitored experiments worldwide, scientists are trying different methods to wean several hundred transplant recipients off anti-rejection drugs.
A small but growing number of successes has scientists edging closer to an understanding of 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 one pays of lifelong immunosuppression is higher than we'd like right now, and you'd like to reduce it," he says.
The quest was spurred by Pittsburgh transplant pioneer Dr. Thomas Starzl's discovery in 1990 of seven persons 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 for ways to force chimerism.
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 slowly are weaned off. Of 120 now being weaned, several dozen are down to one, two or three pills a week.
That directly contradicts today's standard practice of major immunosuppression immediately following surgery. The 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.
Other researchers believe 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 University researchers implanted kidneys into four persons, 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.


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