miércoles, 25 de julio de 2012

Drug May Make Bone Marrow Transplants to Treat Blood Cancers Safer ► NCI Cancer Bulletin for July 24, 2012 - National Cancer Institute

NCI Cancer Bulletin for July 24, 2012 - National Cancer Institute



Drug May Make Bone Marrow Transplants to Treat Blood Cancers Safer

Results from a small clinical trial suggest that a drug used to treat HIV infection may help prevent a potentially lethal complication of bone marrow transplants to treat patients with blood cancers. The drug, maraviroc, appears to work by altering the activity of immune system cells that are chiefly responsible for graft-versus-host disease (GVHD). The findings were published July 12 in the New England Journal of Medicine.
Allogeneic stem cell transplantation is often required to treat patients with leukemia and lymphoma. GVHD occurs when immune cells in the transplanted cell population attack the patient’s body, typically organs such as the liver, skin, and gut.

Dr. Ran Reshef of the University of Pennsylvania Abramson Cancer Center and his colleagues conducted a 38-patient clinical trial to test whether a 33-day course of maraviroc might limit or prevent GVHD. The drug targets a receptor on certain immune cells that helps direct them as they move throughout the body.

Overall, 35 patients could be evaluated, all of whom underwent reduced-intensity conditioning stem cell transplants. In this procedure, lower doses of drugs are used to kill cancer cells and suppress immune cells in the patients’ bone marrow before they receive stem cells. The 35 patients also received maraviroc and two other drugs commonly used to prevent or limit GVHD.

Six months after the transplants, about 6 percent of patients had experienced serious GVHD (grade III and IV)—more than 70 percent lower than what is usually seen after reduced-intensity-conditioning transplants, the authors reported. The treatment was most effective at preventing GVHD in the liver and gut, which can produce debilitating and even fatal outcomes.

In the first 100 days after the transplants, no patient had GVHD in the liver or gut; 6 months after the transplants, the rates were approximately 3 percent and 9 percent, respectively, which Dr. Reshef noted “is still very low.”

The rates of cancer relapse and death were nearly identical to what is typically seen with reduced-intensity conditioning transplants, a finding that Dr. Reshef said supports the hypothesis that maraviroc does not significantly suppress the immune system. “Disease relapse is a major concern of any trial of GVHD prevention,” he explained. “You may reduce GVHD, but you can pay the price of increased relapse. We were encouraged that we did not see this in our trial.”

More studies are needed to better understand the drug’s impact, Dr. Reshef stressed. The Abramson team is planning another small trial to test a longer course of maraviroc treatment, and they have begun discussions with the NCI-supported Blood and Marrow Transplant Clinical Trials Network Exit Disclaimer to conduct a larger, multicenter trial.
This research was supported in part by the National Institutes of Health (P30-CA16520, K24-CA117879, and U01-HL069286).

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