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Drugs limit deadly side effects of graft-versus-host disease

ANN ARBOR, MI V A new class of anti-cancer drugs, currently being tested in human clinical trials, reduces the severity of graft-versus-host disease or GVHD a common and often deadly complication of life-saving bone marrow transplants without suppressing the immune response required to kill lingering cancer cells.

Scientists at the University of Michigan's Comprehensive Cancer Center are the first to study the effect of these drugs, called HDAC inhibitors, in laboratory mice with cancer after the mice received a bone marrow transplant. Results of the U-M study were published online in this week's early edition of the Proceedings of the National Academy of Sciences.

Other studies have shown that high doses of HDAC inhibitors can be an effective anti-tumor agent in mice and humans. Now, U-M scientists have found that low doses of the same drugs have a powerful anti-inflammatory effect. This prevents the production of proteins called inflammatory cytokines, which cause the extensive cell damage seen in GVHD patients. "What's so exciting is that HDAC inhibitors already have been tested as a chemotherapeutic agent in people," says co-author James L.M. Ferrara, M.D., director of the U-M's Blood and Marrow Transplant Program and a professor of internal medicine and pediatrics in the U-M Medical School. "They have relatively little toxicity and the doses required to generate an anti-inflammatory effect are 50- to 100-fold lower than doses needed to kill cancer cells."

If HDAC inhibitors work as well in cancer patients as they did in mice in the U-M study, they could reduce the risk of death, hospitalization and serious side effects associated with bone marrow transplants used to treat leukemia and other related cancers.

More than 5,000 Americans receive allogeneic bone marrow transplants annually. An allogeneic donor is someone other than the patient or the patient's identical twin. Between 500 to 1,000 Americans die from gr
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Contact: Sally Pobojewski
pobo@umich.edu
734-615-6912
University of Michigan Health System
27-Feb-2004


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