Rituximab effective in treating chronic graft-versus-host disease
Mar 24, 2006 - 7:15:00 PM, Reviewed by: Dr. Priya Saxena
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"Our findings validate the preliminary work about the benefits of rituximab for this group of patients. It offers a new line of therapy for individuals for whom, until now, few good options have existed."
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By Dana-Farber Cancer Institute,
A study by Dana-Farber Cancer Institute researchers offers the strongest evidence yet of the effectiveness of a novel therapy for chronic graft-versus-host disease (GVHD), a potentially life-threatening complication of donor bone marrow and stem cell transplants.
The use of the therapy, a drug known as rituximab, grew out of recent discoveries about the human immune system and the interactions between transplanted cells and recipients' own tissue. In the new study, posted on the website of the journal Blood, researchers found that rituximab reduced the severity of chronic GVHD in 70 percent of the study participants who completed at least one course of treatment, including two who experienced complete remissions of symptoms. The benefits, which continued up to a year after therapy, occurred mainly in patients whose skin and musculoskeletal systems were affected by chronic GVHD.
"Our findings validate the preliminary work about the benefits of rituximab for this group of patients," says the study's lead author, Corey Cutler, MD, MPH, of Dana-Farber. "It offers a new line of therapy for individuals for whom, until now, few good options have existed."
Chronic graft-versus-host disease is the most common cause of disease and death among long-term survivors of donor stem-cell transplants for certain forms of cancer and blood diseases, affecting 60-70 percent of long-term survivors. It occurs when immune system cells in transplanted tissue launch an attack on recipients' own tissue, producing problems that can range from a mild rash to diarrhea and fever to life-threatening disorders. Despite therapy that can last months or years, chronic GVHD kills up to a third of all those who survive long-term after stem-cell transplants for leukemia.
Traditionally, scientists have thought that GVHD is caused by T cells, immune system cells whose job is to attack foreign tissue and which enter transplant recipients along with donor stem cells. This thinking has been challenged by research, by Dana-Farber's Jerome Ritz, MD, and others, that indicates that immune system B cells, as well as T cells, play a critical role in GVHD. (T cells are so named because they mature in the thymus gland, while B cells are derived from bone marrow.) This hypothesis gained traction when laboratory studies and small clinical trials showed that rituximab, which specifically targets B cells, could be effective against GVHD.
The new study reinforces those findings with the largest group of chronic GVHD patients yet treated with rituximab. The patients in the study had chronic GVHD that was resistant to the standard therapy of corticosteroids, and were on stable doses of other immune system-suppressing medications. Twenty of the study's 21 participants completed at least one 4-week course of treatment. All had received stem cell transplants at least six months before enrolling in the study.
In addition to reducing the severity of GVHD in nearly three-fourths of the study participants, rituximab enabled 68 percent of the participants to reduce the amount of corticosteroids they were taking by more than 50 percent. Patients reported few side effects of the rituximab therapy.
"We've demonstrated that anti-B cell therapy with rituximab is safe and effective for patients with steroid-resistant chronic GVHD," Cutler says. "It's becoming clearer that treatments for chronic GVHD will need to take account of both T cell and B cell activity in transplant recipients. The success of this approach suggests that anti-B cell therapies cold be tested as part of a strategy for preventing GVHD and treating it in its earliest stages." 
- Published in Journal Blood
www.bloodjournal.org
The study's senior author is Edwin Alyea, MD, of Dana-Farber. David Miklos, MD, PhD, of Stanford University, is co-lead author. Other co-authors include Jesse Levin, Katherine Miller, Carol Reynolds, PhD, Rebecca Macdonell, Haesook Kim, PhD, Mildred Pasek, RN, OCN, Stephanie Lee, MD, MPH, Vincent Ho, MD, Robert Soiffer, MD, Joseph Antin, MD, and Jerome Ritz, MD, of Dana-Farber; and Nathaniel Treister, DMD, Sook-Bin Woo, DMD, Don Bienfang, MD, and Lloyd Klickstein, MD, PhD, of Brigham and Women's Hospital.
Funding for the study was provided by Genentech, Inc., and a grant from the National Heart Lung and Blood Institute.
Dana-Farber Cancer Institute (www.danafarber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
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