Bruce Blazar, M.D.

MINNEAPOLIS/ST. PAUL (August 11, 2009)—The National Institutes of Health has awarded a five-year, $9.5 million project grant to Bruce Blazar, M.D., of the University of Minnesota's Masonic Cancer Center, and Joseph Antin, M.D., and Jerome Ritz, M.D., both with Dana-Farber Cancer Institute in Boston. The grant will be used to further their research on graft-versus-host disease (GVHD), a complication that can occur after a patient undergoes a stem cell transplant for treatment of hematologic malignancies including leukemia, lymphoma, and multiple myeloma.

GVHD occurs when the transplanted donor cells perceive the patient's body as foreign and attack the patient's organs and tissue.

"The disease can be either acute, meaning that it starts within three months of transplant, or chronic, defined as beginning more than three months after transplant and potentially lasting for years," Blazar said. "Our research focus with this grant will be on chronic GVHD. Over the next five years, our goals will include trying to better understand the biology of chronic GVHD, identify the potential for GVHD in patients undergoing stem cell transplant, and beginning clinical trials to test new therapy approaches that can prevent or better treat GVHD in stem cell transplant patients."

Blazar is a Regents Professor in the University's Department of Pediatric Hematology, Oncology and Transplantation, and a leading scientist in the Masonic Cancer Center's Transplant Biology and Therapy Research Program.

Stem cell transplantation is frequently used in the treatment of hematologic malignancies because it results in long-term remissions and potential cures. GVHD can occur after a person receives a stem cell transplant from either a related or unrelated donor. The stem cell transplant patient's immune system can recognize protein differences between the donor and recipient, even when these individuals are "matched" for HLA (human leukocyte antigen) tissue compatibility. As a result, T-cells (a type of white blood cell) from the donor's immune system can launch an attack on the recipient's own tissue, producing problems that can range from a mild rash to diarrhea and fever to life-threatening disorders.

Both the acute and chronic forms of GVHD can lead to serious toxicity in patients who might otherwise be cured of their malignant disease. Work done in the previous years of the grant developed new effective ways of controlling acute GVHD; however, chronic GVHD remains a problem. Research previously performed in Ritz's lab at Dana Farber and in Blazar's lab at the University of Minnesota's Masonic Cancer Center demonstrated that not only are T-cells involved in chronic GVHD, but B-cells producing antibodies against recipient tissues also may play an important role in the development of chronic GVHD. The NIH grant is designed to build on those findings, and to develop new ways to prevent and treat chronic GVHD.

"We are fortunate to have a group of highly committed, creative investigators who both understand the biology of GVHD and how to perform clinical studies," said Antin, chief of the Stem Cell Transplantation Program at Dana-Farber Cancer Institute. "This set of skills has allowed us to select novel agents for testing in transplant patients and design interesting studies with both clinical and biologic endpoints to maximize the knowledge gained in these trials."

The NIH award renews grant funding the team initially received more than five years ago that resulted in more than 40 research publications. More importantly, this initial research established a new paradigm for the cause of acute of GVHD and suggested new mechanisms to treat it.

During the next five years, Blazar and his Dana-Farber colleagues will use the NIH program project grant for research that advances the scientific understanding of chronic GVHD, its prevention and treatment.

"NIH funding has been tremendously helpful and has allowed us to develop a much better understanding of the complex response to normal recipient tissues that occurs after hematopoietic stem cells transplantation," said Ritz, director of Dana-Farber's Connell and O'Reilly Families Cell Manipulation Core. "This has led to new therapies that are now being tested by Dr. Antin and his colleagues, and I expect that these new studies will also lead to new approaches for prevention and treatment of chronic GVHD and improved outcomes for patients undergoing stem cell transplantation."

Masonic Cancer Center, University of Minnesota is part of the University's Academic Health Center. It is designated by the National Cancer Institute as a comprehensive cancer center for cancer research, treatment, and education. For more information, call 612-624-2620 or visit www.cancer.umn.edu.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research 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.

Media contacts:

Mary Lawson, Masonic Cancer Center 612-203-0819, mlawson@umn.edu

Sara Martin, Academic Health Center 612-626-7037, buss@umn.edu