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February 17

Protein level predicts who will develop deadly complication after marrow transplant, U-M researchers find

Inflammation marker measured at 1 week tied to 1-year survival rate

ANN ARBOR, MI – Researchers could determine one week after a bone marrow transplant which patients were likely to develop a serious and deadly complication, making them candidates for preventive treatment before any symptoms occur.

John Levine, M.D.Researchers at the University of Michigan Comprehensive Cancer Center measured the level of a protein called tumor necrosis factor, or TNF, seven days after patients received a bone marrow transplant. TNF, a trigger for inflammation, is known to be elevated in people who develop graft vs. host disease, the most common serious side effect of a bone marrow transplant from a donor.

Bone marrow transplant is a lifesaving treatment given to children or adults with certain types of cancer, such as leukemia or lymphoma, or to people with some blood or immune disorders. A transplant allows higher doses of chemotherapy to be used to destroy cancer, because the damaged bone marrow is replaced by the transplanted healthy marrow. But the complicated treatment carries a risk of the body rejecting the new bone marrow, a condition called graft vs. host disease, or GVHD. The transplanted immune cells can attack the patient’s skin, liver and gastrointestinal cells, triggering a massive inflammatory reaction that can kill the patient.

The study looked at 170 patients, 94 of whom went on to develop graft vs. host disease, a condition in which the transplanted immune system attacks the patient’s normal tissue. Those 94 patients had elevated levels of the TNF-receptor protein a week after their transplant – before they showed any symptoms of graft vs. host disease. Researchers also found patients whose TNF level was elevated at seven days had a 20-point lower survival rate: 62 percent were alive after a year, compared to 85 percent of those with a lower TNF.

“This suggests we could target patients to prevent graft vs. host disease based on their post-transplant level of TNF. If we can develop a test that can reliably predict this complication, we can then look at treating it before any symptoms develop. This is one small step in a long road to making transplants safer and more effective,” says study author John Levine, M.D., associate professor of pediatrics and internal medicine at the U-M Medical School.

Levine will present these findings Friday, Feb. 17, 2006, at the American Society for Blood and Marrow Transplant annual meeting.

Research led by James Ferrara, M.D., director of the Blood and Marrow Transplantation Program at the U-M Comprehensive Cancer Center has previously linked TNF to graft vs. host disease.

“TNF is known to play a role in a variety of inflammatory or autoimmune diseases, including septic shock, rheumatoid arthritis and Crohn’s disease. Anti-TNF drugs are already FDA-approved and available on the market. We are currently conducting a clinical trial using one of these drugs, etanercept, in clinical trials to see if it can prevent or treat GVHD,” says study author Carrie Kitko, M.D., a pediatric fellow at the U-M Health System.

About 40 percent to 50 percent of all patients who receive a bone marrow transplant will develop GVHD, and 30 percent will die from this complication. The
U-M Comprehensive Cancer Center performs 250 blood and marrow transplants each year, in both children and adults. For more information, visit or call the Cancer AnswerLine at 800-865-1125.

The research was funded by a Doris Duke Charitable Foundation Distinguished Clinical Scientist Award.

Reference: American Society for Blood and Marrow Transplant annual meeting, Feb. 17, 2006, Honolulu, Hawaii.

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