HIV drug can prevent complications after stem-cell transplant
A drug used in the treatment of human immunodeficiency virus (HIV) helped lower the risk of graft-versus-host disease (GvHD) in persons with blood cancer who underwent allogeneic hematopoietic stem-cell transplantation (HSCT) to rebuild bone marrow.
Maraviroc, which was approved for HIV treatment in 2007, inhibits the chemokine receptor CCR5. Chemokines direct immune cells to specific organs, and the current research indicates that maraviroc can redirect immune cells away from sensitive organs—namely, the liver and the gut—thus preventing the deadly complication of GvHD after stem-cell transplantation.
GvHD occurs when the newly transplanted immune cells attack healthy tissue they perceive as foreign. Patients receive immunosuppressive drugs posttransplant, but these agents can leave the already weakened immune system even more vulnerable to life-threatening infections and cancer recurrence.
Treatment with maraviroc “is a novel way for us to try to decrease treatment-related complications among bone-marrow transplant patients without also reducing their new immune system's ability to attack their cancer,” explained the study's lead author, Ron Reshef, MD, in a statement issued by the University of Pennsylvania School of Medicine in Philadelphia. Reshef, a professor of hematology-oncology at the school, is also a member of the Hematologic Malignancies Research Program at Penn's Abramson Cancer Center. His group's findings appear in The New England Journal of Medicine (2012;367:135-145).
Reshef and colleagues evaluated 35 high-risk HSCT patients with acute myeloid leukemia (AML), myelodysplastic syndrome, lymphoma, myelofibrosis, and other blood cancers. All participants received tacrolimus and methotrexate, the standard regimen for GvHD prevention. Beginning 2 days posttransplant, the patients were also put on a 33-day course of maraviroc.
No cases of GvHD in the gut or liver, the most severe forms of the illness, developed in the first 100 days after transplant, and the cumulative incidence was still low by day 180 (5.9±4.1%). At the 6-month mark, only 6% of the patients had severe GvHD, compared with 22% of similar patients who received standard immunosuppressive therapy without maraviroc. At that time point, liver and gut involvement were seen in 15% of the patients with GvHD who had taken maraviroc, compared with 27% in the patients who had not received this medication.
One year after HSCT, cumulative incidence of GvHD was nearly double in the non-maraviroc group (29%) compared with the maraviroc group (15%).