Drug-free breakthrough in transplant patients

Massachusetts researchers have been able to wean four of five kidney transplant patients off of anti-rejection drugs, a feat that could eventually lead to a sharp reduction in use of the expensive, side effect-ridden medications.

By simultaneously giving recipients bone marrow from living donors, physicians were able to induce what is known as a state of tolerance, in which the recipient’s immune system does not recognize the new organ as foreign.

The procedure was more remarkable in that the recipients were given kidneys that were not a perfect tissue match, making them more susceptible to rejection.

Based on experiments in monkeys, “There is reason to hope these patients will be off drugs for the rest of their lives,” said Dr. David Sachs of Massachusetts General Hospital, the lead author of the report in Thursday’s New England Journal of Medicine.

The technique will not alleviate the shortage of donors, and patients who have already received transplants will not be able to stop taking medications, but the procedure could have a major impact on transplant recipients if it can be replicated in larger studies.

Anti-rejection drugs can cause a variety of problems, including excessive hair growth, bloating, tremors and kidney failure.

In the new procedure, developed in animals during a 30-year period, the team gave the prospective recipients drugs and radiation to weaken their immune systems and destroy T cells, the primary immune system component involved in tissue rejection.

A few days later, the patients received the transplant and an infusion of bone marrow from the donor. The patients initially received anti-rejection drugs, but were successfully weaned off them after eight to 14 months.

The procedure was successful in the first two patients, one of whom has now been drug-free for more than five years. The third patient, however, rejected the transplant and had to have a second. Examining the patient, the team observed a high level of another immune cell called B cells.

In the final two patients, they modified the protocol to add antibodies against B cells. Both patients were weaned from drugs and have been drug-free for two to three years.

Sachs now plans to study the procedure in an additional 15 to 20 patients, and a team at Northwestern Memorial Hospital in Chicago is also planning to study it in 20 patients.

thomas.maugh@latimes.com