Antiretroviral Drug May Prevent Graft-Versus-Host Disease
The drug Selzentry® (maraviroc), which is typically used to treat HIV infection, may help prevent graft-versus-host disease (GVHD), a potentially lethal complication of stem cell transplants, according to the results of a study published in the New England Journal of Medicine.
Stem cell transplantation (also called bone marrow transplantation) is a procedure often used to treat patients with leukemia and lymphoma. The procedure first involves the delivery of high-dose chemotherapy and/or radiation, which destroys more cancer cells than standard doses. Unfortunately, the high-dose therapy also damages normal cells—most notably, the blood-producing stem cells in the bone marrow. In order to repair this damage, a stem cell transplant is used to “rescue” or restore bone marrow blood and immune cell production. In an allogeneic transplant, the stem cells come from a donor.
One common complication of allogeneic stem cell transplantation is graft-versus-host disease (GVHD), which refers to a condition where the donor cells attack the cells in the recipient’s body, especially those in the skin, gastrointestinal tract, and liver. GVHD can cause rash, jaundice, liver disease, diarrhea, and can also increase the susceptibility to infection. GVHD can be acute or chronic-and can be life threatening. Despite 40 years of intensive research, GVHD remains a major stumbling block to the success of allogeneic stem cell transplantation.
Selzentry is an antiretroviral drug in a class of medications called CCR5 co-receptor antagonists. It works by slowing the spread of HIV in the body. The drug targets a receptor on certain immune cells that helps direct them as they move throughout the body.
Researchers from the University of Pennsylvania Abramson Cancer Center conducted a clinical trial to evaluate the effects of Selzentry on GVHD. The study included 35 patients who underwent stem cell transplantation and received a 33-day course of Selzentry along with two other drugs commonly used to prevent or limit GVHD (tacrolimus and methotrexate). Selzentry was given orally twice daily starting 2 days before transplantation until day 30.
Six months after transplantation, approximately 6 percent of patients had experienced grade 3 or 4 GVHD—which was an approximately 70 percent reduced incidence rate from what is normally seen. Treatment with Selzentry appeared to be most effective at preventing GVHD in the liver and gastrointestinal tract, which are often the most dangerous cases. During the first 100 days after transplantation, no patients experienced GVHD in the liver or gastrointestinal tract; six months after transplantation, approximately 3 percent of patients experienced GVHD in the liver and 9 percent in the gastrointestinal tract—which represented very low rates.
Notably, treatment with Selzentry did not appear to increase the relapse rate—as the rate of cancer relapse and death were nearly identical to the rates typically seen in the transplantation setting.
The researchers concluded that treatment with Selzentry appears to limit or prevent GVHD after allogeneic stem cell transplantation, perhaps because the drug works to alter the activity of immune system cells that are primarily responsible for development of GVHD. More research is planned to test a longer course of treatment with Selzentry.
Reshef R, Luger S, Hexner EO, et al. Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease. New England Journal of Medicine. 2012; 367:135-145.