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HIV drug reduces graft-versus-host disease in stem cell transplant patients, Penn study shows
Date:12/13/2011

around the body in a random way. There is a very distinct and well orchestrated process whereby cells express particular receptors on their surface that allow them to respond to small proteins called chemokines. The chemokines direct the immune cells to specific organs, where they are needed, or in the case of GvHD, to where they cause damage."

Thirty-eight patients with blood cancers, including acute myeloid leukemia, myelodysplastic syndrome, lymphoma, myelofibrosis, and others, enrolled in the phase I/II trial. All patients received the standard GvHD prevention drugs tacrolimus and methotrexate, plus a 33-day course of maraviroc that began two days before transplant. In the first 100 days after transplant, none of the patients treated with maraviroc developed GvHD in the gut or liver. By contrast, 12.5 percent of patients in the control group developed GvHD in the gut and 8.3 percent developed it in the liver within 100 days of their transplant.

The differential impact of maraviroc on those organs indicates that the drug is working as expected, by limiting the movement of T lymphocytes to specific organs in the body. Maraviroc works by blocking the CCR5 receptor on lymphocytes, preventing the cells from trafficking to certain organs. The researchers saw no effect on skin GvHD, so they theorize that the CCR5 receptor might be more important for sending lymphocytes into the liver and the gut than for the skin.

After 180 days, the benefit of maraviroc appeared to be partially sustained in patients and the cumulative incidence of gut and liver GvHD rose only to 8.8 percent and 2.9 percent, respectively. The cumulative incidence in the control group, however, remained higher, at 28.4 percent for gut and 14.8 percent for liver GvHD. Based on those data, the research team plans to try a longer treatment regimen with maraviroc to see if they could prolong the protective effect.

Maraviroc treatment did not appear to increase treatment
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Contact: Holly Auer
holly.auer@uphs.upenn.edu
215-200-2313
University of Pennsylvania School of Medicine
Source:Eurekalert

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