Drug Reduces Graft-Versus-Host After Stem Cell Transplant

Chemokine receptor CCR5 antagonist maraviroc inhibits lymphocyte chemotaxis

THURSDAY, July 12 (HealthDay News) -- The chemokine receptor CCR5 antagonist maraviroc, which blocks lymphocyte trafficking, is safe and reduces the incidence of acute graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem-cell transplantation, according to a phase I and II study published in the July 12 issue of the New England Journal of Medicine.

Ran Reshef, M.D., from the University of Pennsylvania in Philadelphia, and colleagues examined the in vitro effect of maraviroc and its safety and efficacy when added to standard GVHD prophylaxis in 38 high-risk patients undergoing allogeneic hematopoietic stem-cell transplantation. Maraviroc was given orally twice a day, starting two days before transplantation until day 30.

The researchers found that, in vitro, maraviroc inhibited lymphocyte chemotaxis and CCR5 internalization, without impairing T-cell function or hematopoietic-cell colonies. The mean cumulative incidence rate of grade II to IV acute GVHD was 14.7 percent on day 100 and 23.6 percent at day 180 in 35 patients who could be evaluated. The mean cumulative incidence of grade III or IV GVHD was 5.9 percent at day 180, largely attributed to low rates of acute liver and gut GVHD which were absent before day 100. At one year the mean cumulative rate of death not preceded by disease relapse was 11.7 percent, and relapse and infection rates were not excessive.

"In this study, inhibition of lymphocyte trafficking was a specific and potentially effective new strategy to prevent visceral acute GVHD," Reshef and colleagues conclude.

The study was partially funded by Pfizer. Several authors disclosed receiving financial support from Pfizer and other pharmaceutical companies.

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