Transplant Drug Has Good, Bad Side

A drug that stops the immune system from attacking a newly transplanted heart also increases the risk of life-threatening infections in some patients, researchers report.

The drug, daclizumab (marketed as Zenapax), has already proven successful in kidney transplants and works by blocking immune cells that attack foreign tissue. And in a trial that included 434 heart transplant patients, the drug did decrease the rate of rejection, say researchers reporting in the June 30 issue of the New England Journal of Medicine.

Only 25.5 percent of the patients who got daclizumab experienced rejection in the first six months after the surgery, compared to 41.3 percent of those who got a placebo, according to the study, which was funded by the drug's maker, Roche Laboratories.

However, six of the patients placed on the drug died of infections. No such deaths occurred in the placebo group.

The reaction of cardiologists to those numbers differs greatly.

"I am certain that I would not be willing to trade even a small increase in the risk of death from infection for a reduction in the risk of histologic rejection," Dr. Jeffrey D. Hosenpud, a cardiologist at St. Luke's Medical Center in Milwaukee, commented in an accompanying editorial.

But study lead researcher Dr. Ray E. Hershberger, a transplant cardiologist at the Oregon Health and Science University, has a different view. According to Hershberger, the study shows that infection risk was increased only in patients who got both daclizumab and another form of therapy, called cytolytic therapy. Cytolytic treatment is aimed not at blocking the immune cells, but at killing them, he said.

It took "an enormous amount of effort" sifting through the study data to establish that connection, Hershberger said. The use of daclizumb plus cytolytic therapies in combination for heart transplant patients "should be avoided in usual clinical practice," he said. Roche Laboratories has already issued a warning to that effect.

Hershberger said he does use daclizumab in his practice -- but with great care. "We use this antibody and all others selectively," he said. "We tailor therapy to every patient. In heart transplantation, one size does not fit all."

Dr. Randall C. Starling, director of the Cleveland Clinic's heart failure and transplant program, who took part in the study, said essentially the same thing. "We do not use any type of antibody preparation for all of our patients," he said. "We use them selectively."

Starling is not ready to write off the clinical value of avoiding transplant rejection episodes. The study added valuable information about immune therapy, he said, because "this is the largest randomized trial to test whether such an antibody is efficacious." But the final word on the treatment is still not in, Starling said.

"Only with time and extended follow-up will we know if reducing rejection up front translates into better survival over the long run," he said.

More information

You can learn more about daclizumab from the National Library of Medicine.

Thalidomide Helps Combat Multiple Myeloma

A treatment called Thal-Dex that combines the once-banned drug thalidomide with the steroid dexamethasone works better than conventional chemotherapy in the treatment of multiple myeloma, according to a new Italian study.

Multiple myeloma in an incurable and painful cancer of the bone marrow. Many patients live less than five years after being diagnosed with the disease. Autologous (self-donor) stem cell transplants can help extend patient survival. Chemotherapy is done a few months before stem cell transplant to reduce the number of cancer cells and improve the odds of stem cell transplant success.

The new study included 100 multiple myeloma patients who received Thal-Dex before stem cell transplant and 100 patients who received traditional "VAD" chemotherapy before transplant. VAD is a combination of three drugs -- vincristine, adriamycin and dexamethasone.

As reported in the July 1 issue of the journal Blood, patients who received Thal-Dex were more likely to have successful transplant results -- 76 percent of the Thal-Dex patients showed at least a partial remission compared with 52 percent of VAD patients. The Thal-Dex patients also showed more reduction in the size of their tumors.

Fifteen percent of patients taking Thal-Dex experienced deep vein thrombosis (dangerous blood clots), however. This side effect was successfully treated using anti-coagulants. The study authors said more research is needed to help predict which patients will suffer deep vein thrombosis when treated with Thal-Dex.

In the 1960s, thalidomide was used by some pregnant women to treat morning sickness. But women who took the drug gave birth to children with severe birth defects such as missing or shortened limbs, according to the National Institutes of Health.

"It's time to look at thalidomide in a new light," Dr. Michele Cavo, professor at the University of Bologna and lead study author, said in a prepared statement. "It's earned its place in modern medicine. Thalidomide has proven to be a highly effective, relatively safe, and more comfortable treatment for patients with multiple myeloma than traditional chemotherapy."

More information

The American Cancer Society has more about multiple myeloma