New Drug Cuts Risk of Post-Transplant Graft-vs.-Host Disease

Results were now presented at the 2012 Annual Meeting of the American Society of Hematology.

“Graft-vs.-host disease is the most serious complication from transplant that limits our ability to offer it more broadly. Current prevention strategies have remained mostly unchanged over the past 20 years. This study has us cautiously excited that there may be a potential new way to prevent this condition,” said lead author Sung Choi, MD and assistant professor of pediatrics at UM.

Vorinostat is of a class of drugs targeting histone deacetylases (different from the molecules targeted by traditional treatments) and is currently approved by the US Food and Drug Administration to treat certain types of cancer. But researchers led by senior author Pavan Reddy, MD and associate professor of internal medicine at UM, had found that vorinostat had anti-inflammatory effects as well – which they hypothesized could be useful in preventing graft-vs.-host disease.

Prof. Choi presented data on the first 47 patients enrolled on the study at the UM Comprehensive Cancer Center and Washington University. Participants were older adults who were undergoing a reduced-intensity bone marrow transplant with cells donated from a relative. Patients received standard medication used after a transplant to prevent graft-vs.-host disease. They also received vorinostat, given as a pill taken orally. Vorinostat was found safe and tolerable, with manageable side effects. In addition, rates of patient death and cancer relapse among the study participants were similar to historical averages. The results mirror those found in the laboratory using mice.

“This is an entirely new approach to preventing graft-vs.-host disease,” said Prof. Choi. “Vorinostat has a dual effect as an anticancer and an anti-inflammatory agent. That’s what’s potentially great about using it to prevent graft-vs.-host, because it may also help prevent the leukemia from returning,” added Prof. Choi. The researchers hope next to test vorinostat in patients receiving a transplant from an unrelated donor, which carries an even greater risk of graft-vs.-host disease.

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University of Michigan Comprehensive Cancer Center