Pioneering Immunosuppression...woohoo!

http://www.post-gazette.com/pg/06205/708203-114.stm

Pittsburgh, Pa.
Monday, July 24, 2006

Less drug better for transplant survival
Immune system can accept donor tissue
Monday, July 24, 2006

By Anita Srikameswaran, Pittsburgh Post-Gazette

A protocol that allows children who get intestinal transplants to minimize the drugs needed to prevent rejection appears also to improve their survival chances.

The regimen avoids steroids and encourages the immune system to welcome the donor tissue, explained Dr. Rakesh Sindhi, co-director of pediatric transplantation at Children's Hospital.

"There's no question, as we look back at our data, that using less drug has been better for these patients," he said. "Today we'll often send patients home with barely about three to four medicines. It used to be there would be about 10 to 15 of them."

Dr. Sindhi will present findings today and tomorrow from four studies at the World Transplant Congress in Boston.

One of them reviewed 75 children who between 2002 and 2006 had transplants of small bowel either alone or with a liver at Children's. Three years after their operations, 84 percent were still alive.

Before transplant physicians implemented the new protocol, two-year survival rates were about 70 percent, comparable to international figures, Dr. Sindhi noted.

The new approach, which is now routinely used at Children's, is definitely better because patients live longer and need fewer drugs, he said.

It's based on a premise proposed by transplant pioneer Dr. Thomas Starzl, of the University of Pittsburgh, and others that creating the right balance between patient cells and donor cells will favor the development of immunological tolerance.

Near the time of transplantation, patients get a drug called thymoglobulin, which depletes the number of immune system T-cells that could attack the donor organ.

No steroids are given after the surgery, Dr. Sindhi said. "That's our way of starting the drug reduction process right up front."

Steroids can slow growth in children and lead to diabetes and hypertension, among other problems.

A standard dose of an anti-rejection drug called Prograf is administered initially, but after about three months, it is rapidly reduced. In general, the intestinal transplant patients require about half the amount of the drug than had been the norm, and no steroids, the doctor said.

The same approach is being used in the transplantation of other organs at Children's.

Liver transplant recipients might get to the point where they don't need the medicine anymore, or only need it every other day in minimal doses. The liver has a greater capacity to regenerate, so it can recover more easily than the intestine or kidney from mild rejection episodes, Dr. Sindhi said.

"If rejection occurs, we treat it the same as we always have," with steroids and more medicine, he said. But "using this approach, we've noticed that rejections are not any worse than before."

Renee Rosner's daughter Adelynn, now 4, got a liver transplant when she was 9 months old and weighed 13 pounds. The North Huntingdon girl had biliary atresia, in which the ducts that drain bile from the liver are obstructed.

Adelynn had the thymoglobulin protocol during her transplant, but did need steroids because of mild rejection.

"She was the classic steroid baby," her mother said. "She was chubby with the big moon face, which for us, believe it or not, was almost a relief because she had been so skinny."

But Ms. Rosner was glad when the steroids were tapered, and Adelynn no longer needs them. The child used to take a total of 7 milligrams of Prograf each day, and now takes 2 milligrams once a day. That will soon be reduced again, Ms. Rosner said.

"The goal would be the need for no immunosuppressor [drug] at all," she said. " Quite honestly, I would be very happy with every other day."

As the Prograf dose has come down, Adelynn is sleeping better, her mother said. And if she no longer needs the antirejection drug, she should also be able to stop taking other medications that counteract its side effects.

(Anita Srikameswaran can be reached at anitas@post-gazette.com or 412-263-3858. )