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| |  Statins May Protect Stem Cell Transplant Recipients From Graft-Versus-Host Disease SEATTLE -- December 4, 2009 -- Statins may protect stem cell transplant recipients from one of the most serious complications of the life-saving cancer therapy: graft-versus-host disease (GVHD). That’s the finding from a retrospective study reported in the November 4 edition of the journal Blood. According to researchers from the Fred Hutchinson Cancer Center, Seattle, Washington, of 567 patients who underwent haematopoietic cell transplantation from matched sibling donors between 2001 and 2007, patients whose donors had been taking statins at the time of stem cell donation experienced no severe acute GVHD. About 15% of the stem cell donors in the study were taking statins at the time of transplant. Normally, between 10% and 15% of transplant patients would be expected to develop severe acute GVHD, according to the study’s senior author Marco Mielcarek, MD, Clinical Research Division, Fred Hutchinson Cancer Center. No such protection from severe acute GVHD was observed if only the patient was taking a statin, according to the study. There was some indication that protection against severe GVHD was even stronger when both patient and donor had been on statin medications; however, the number of patients in this group was too small to be statistically significant. The researchers also found that only those transplant patients with statin-treated donors who received cyclosporine-based immunosuppression therapy after transplantation were protected from severe GVHD. Patients with statin-treated donors who received a similar drug, tacrolimus, did not experience the same GVHD-protection. The study also found that the greatest statin protection occurred against severe GVHD of the gastrointestinal tract. GVHD, a common side effect in patients who receive blood stem cell transplants from related or unrelated donors, can cause a variety of problems, including skin rashes, diarrhea and liver inflammation. Acute GVHD often occurs in the first 3 months after a transplant and can lead to mortality as high as 50% if it is severe. Dr. Mielcarek, first author Marcello Rotta, MD, Clinical Research Division, Fred Hutchinson Cancer Center, and colleagues undertook the study because previous research showed that statins have anti-inflammatory effects and have been found to improve control of other inflammatory diseases such as rheumatoid arthritis. Recently, studies using mouse models of stem cell transplantation have shown protection against lethal acute GVHD when the donors and recipients had been treated with statins before transplant. The exact mechanism of how statins protect against GVHD is not known. “In the literature, a multitude of possible mechanisms are discussed by which statins may influence immune function,” Dr. Mielcarek said. “One is cell adhesion, the stickiness of cells that influences how donor T cells that cause GVHD can migrate to certain target tissues. Another is how statins interfere with intracellular signaling in T cells. Statins may dampen the activity of allo-reactive T cells and prevent them from initiating the inflammatory cascade that’s required to cause GVHD.” Grants from the National Institutes of Health and The Dana Foundation funded this research.
SOURCE: Fred Hutchinson Cancer Center
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