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Thalidomide: is there a silver lining?

Thalidomide: Is there a silver lining?

Once exiled from medicine for thesevere birth defects it can cause, the drug thalidomide may have found a respectable role in preventing the severe reaction associated with transplanting tissues.

According to Georgia B. Vogelsang ofthe Johns Hopkins University School of Medicine in Baltimore, thalidomide is being used successfully there to treat graft-versus-host disease (GVHD) in a small group of bone marrow recipients. She reported preliminary results this week in San Diego at the American Cancer Society's annual Science Writers' Seminar.

In the late 1950s, women given thalidomideas a sleep-inducing and anti-morning sickness drug while pregnant ran the risk of giving birth to infants who lacked arms or legs. It is "one of the most notorious drugs ever introduced,' says Vogelsang.

Nevertheless, Vogelsang believes thalidomidemay redeem itself in the transplantation field. Although bone marrow transplants often are used to treat leukemia, aplastic anemia and certain genetic disorders, there can be serious setbacks. Because bone marrow contains a large number of cells capable of an immune response, clinicians are careful to match a recipient with donor bone marrow through compatibility testing. However, in 40 to 60 percent of these grafts, the donor bone marrow (graft) recognizes the recipient (host) as foreign and "attacks.' The potentially fatal GVHD that results may be acute or chronic, with symptoms that include mouth ulcers, skin problems and liver failure. To fight GVHD, the immunosupressant cyclosporine currently is the drug of choice; but its high toxicity and slow-acting effects reduce its usefulness.

In the search for alternatives, studieshave shown that cyclosporine and thalidomide influence the same type of immune cell. This, coupled with earlier observations in the 1960s that thalidomide may have caused improvement of leprosy, pointed the way to thalidomide, says Vogelsang.

Encouraged by animal studies, the researchershave recently administered thalidomide to four bone marrow recipients, two with acute GVHD and two with the chronic form. In the present scheme, cyclosporine is being given in tandem with the thalidomide, but in lower doses and for shorter periods of time than usual. "Our real hope is that [thalidomide] will be complementary to cyclosporine,' explains Vogelsang, who says three of the four patients have "responded beautifully.'

One of those patients, who had sufferedfrom GVHD for three years, is regaining normal hair and skin growth, as well as limb mobility lost through thickening of the skin. Vogelsang adds that concurrent studies in England and France are showing similar overall positive results.

Vogelsang and her co-workers are planningstudies of thalidomide's effects on solid-organ transplants, but two problems arise with extended use of the drug. First, while the bone marrow recipients have been made sterile by previous treatment, other organ recipients may still be capable of pregnancy. Second, given the huge liability risk, no U.S. drug company has been willing to manufacture the compound. Therefore, Vogelsang is trading skin-disease drugs for thalidomide "on a pill for pill basis' with a dermatologist in Brazil, where the drug is made for treatment of leprosy.

Whether thalidomide becomes the prodigalson that is warmly welcomed home remains a question to be answered by further research. But, says Charles A. Coltman of the Cancer Therapy and Research Center in San Antonio, Tex., the use of thalidomide "may well be one of the most important advances in bone marrow transplantation.'
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Title Annotation:research on use in bone marrow transplants
Author:Edwards, Diane D.
Publication:Science News
Date:Mar 28, 1987
Previous Article:AIDS drug approved, vaccine tested.
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