Hutchinson Center researchers have developed a new drug therapy that significantly reduces death from gastrointestinal graft-vs.-host disease in allogeneic stem-cell transplant patients. By adding a widely used topical corticosteroid to the standard GVHD treatment, researchers found it kept the potentially deadly side effect in remission and reduced death by 46 percent one year after therapy.
A reformulation of beclomethasone dipropionate (BDP) into two different pills specifically releasing the anti-inflammatory drug into the stomach and mid-small intestine prevented relapse of gastrointestinal GVHD and allowed those patients to be on a shorter treatment course of high-dose prednisone. Findings of the multi-center phase III clinical trial were recently published in the online edition of the journal Blood. The lead author is Dr. David Hockenbery, of the Clinical Research Division. Hockenbery is also a professor of medicine/gastroenterology at the University of Washington School of Medicine.
About 60 percent of patients who receive an allogeneic stem-cell transplant to treat blood cancers such as acute and chronic myelogenous leukemia, acute lymphocytic leukemia and non-Hodgkin's lymphoma develop gastrointestinal GVHD as a major side effect of being infused with donor stem cells. Those who show gastrointestinal symptoms of the disease usually receive a two- to four-week course of high-dose systemic prednisone therapy that is then tapered slowly. However, that drug is a double-edged sword, Hockenbery said. On one hand, it is designed to suppress the donor cells so GVHD can be controlled. But suppressing the immune system also makes patients susceptible to potentially fatal infections.
The idea to reformulate BDP into an oral form for stem-cell transplant patients belongs to study co-author Dr. George McDonald, also of the Clinical Research Division and a professor of medicine/gastroenterology at UW. McDonald initiated the early trials of oral BDP with funding from a U.S. Food & Drug Administration Orphan Products Development Grant. Fifteen other centers in the United States and France participated in the study.
The FDA is expected to decide whether to approve use of the oral form of the drug by July. If approved, it would be only the second drug approved by the FDA for treatment of GVHD in stem-cell transplant recipients.
To learn more about this study, visit www.bloodjournal.org/cgi/content/abstract/blood-2006-05-021139v1.