Procedure Spares Organ Recipients a Life of Drugs ; In Trials, Therapy 'Fooled' Hosts' Immune System

Jan 24, 02:46 PM

In what's being called a major advance in organ transplant procedure, doctors say they have developed a technique that could free many patients from having to take anti-rejection drugs for the rest of their lives.

The treatment involves weakening the patient's immune system, then rebuilding it with cells from the bone marrow of the organ donor. The result is an immune system that tolerates cells from both a donor and a patient, allowing transplant recipients to thrive without drug therapy.

"There's reason to hope these patients will be off drugs for the rest of their lives," said Dr. David Sachs of Massachusetts General Hospital in Boston, who led the research published in today's New England Journal of Medicine.

The approach is still in its infancy, with five successful cases reported out of almost a dozen attempts.

The goal is to eliminate the need for the anti-rejection medications that revolutionized transplants starting in the 1960s by suppressing the immune system's instinct to attack a donated organ. The drugs leave patients vulnerable to infections, and can raise the risk of cancer, kidney failure and other complications with long- term use.

The procedure may "change the whole game of transplantation," said Dr. Thomas Starzl from the University of Pittsburgh Medical Center, who performed the first liver transplant in 1963 and reviewed the studies. "You have two immune systems learning to coexist with each other," he said.

Four out of five patients who received kidney transplants from living donors have been free from medication for as long as 5.3 years in the lead report from Massachusetts General Hospital and Harvard Medical School. The donors and the patients weren't perfectly matched for a transplant, a trait that increases the odds of rejection or the graft attacking the host.

Patients first got intense treatment with chemotherapy, radiation and a cocktail of immune-suppressant drugs. The kidney transplant was followed by an intravenous dose of bone marrow taken from the donor, in each case either a parent or sibling of the recipient. The stem cells from the marrow reprogram the body by allowing new immune cells to grow that don't try to attack the donated organ.

"We're fooling the immune system into thinking the donor is part of itself," said Sachs.

The patients took anti-rejection drugs but were weaned several months later. In the one case that failed, the patient had a second kidney transplant and has been on medications since.

The approach is quite extreme, with patients trading intense therapy to suppress the immune system in the beginning in an effort to avoid lower doses for the rest of their lives, said Dr. Stuart M. Flechner, a professor of surgery and a transplant urologist at the Cleveland Clinic in Ohio. The long-term results are still unclear, he said in a telephone interview.

"It's developmental, it's experimental," said Flechner, who emphasized that the approach should be done only at centers with experience in the process. "It's exciting, but the jury is still out. This is a work in progress."

As promising as the treatment is, Sachs said it won't solve the country's organ shortage problem. Nearly 98,000 people are on the waiting list, according to the United Network for Organ Sharing.

For Jennifer Searl, a Gloucester, Mass., librarian and the first patient of the Massachusetts researchers, the new approach has been miraculous.

Searl was 12 years old when a routine camp physical in 1993 found she had only 15 percent function in her kidneys. She quickly had a conventional transplant with a kidney donated by her father. The immune-suppressing drugs, 20 pills daily, wreaked havoc with her health, causing hypertension, cataracts, weak bones and myriad other conditions. Warts caused by a rampant virus covered her feet, making walking difficult.

Almost a decade later, Searl had another transplant, this time with a kidney and bone marrow donated by her mother using the new approach at Massachusetts General. She was successfully weaned from the drugs in 2003. Her health has fully recovered and she is now a marathon runner who enjoys pushing her physical limits.

"I would have done anything to have a chance at living a somewhat normal life," Searl said. "A conventional transplant is just exchanging one illness for another. It's only now that I'm a normal, healthy person. I can't believe how good I feel. I don't want to waste that."

Another team from Stanford University School of Medicine used perfectly matched donors and a less aggressive pre-treatment to wipe out the immune system. One of six patients, a man who got a kidney from his older brother, has been free from immune-suppressing drug therapy for more than two years.

The treatment led to a hybrid immune system, with an even mix of immune system cells from the patient and his brother, said Dr. John Scandling, medical director of the adult kidney and pancreas transplant program at Stanford. Two subsequent patients weren't able to halt drug therapy, and three others are early in the process, the researchers said.

"Our hope is that with this protocol, we can establish normal kidney function without these medications, and that will prolong these individuals' life expectancy," he said. The patient in the study is active, employed and has a family. "We still have to consider him treated and not cured, but we do hope this will be a cure," Scandling said.

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This article contains material from Bloomberg News and The Associated Press.

(c) 2008 Record, The; Bergen County, N.J.. Provided by ProQuest Information and Learning. All rights Reserved. Procedure Spares Organ Recipients a Life of Drugs ; In Trials, Therapy 'Fooled' Hosts' Immune System
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