Protein levels predict bone marrow transplant survival

Feb 19 2006

Researchers say that protein levels can predict which bone marrow transplant patients are likely develop a deadly complication a week after the procedure and well before any symptoms occur.

The inflammation marker measured at one week was, they say, linked to a one year survival rate.

According to the study by researchers at the University of Michigan Comprehensive Cancer Center it was found that elevated levels of a protein called tumor necrosis factor, or TNF, measured a week after patients received bone marrow transplants, were found among those who later developed a serious and deadly complication, making them candidates for preventive treatment before any symptoms occur.

TNF is a trigger for inflammation and 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.

The study looked at 170 patients, 94 of whom went on to develop graft vs. host disease.

Lead author of the study John Levine, M.D., associate professor of pediatrics and internal medicine at the U-M Medical School, says the results suggest patients could be targeted to prevent graft vs. host disease based on their post-transplant level of TNF.

Bone marrow transplants are 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.

However 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, presented at the American Society for Blood and Marrow Transplant's annual meeting in Honolulu, looked at 170 patients, 94 of whom went on to develop graft vs. host disease.

The 94 patients had elevated levels of the tumor necrosis factor protein a week after their transplants.

Researchers also found that patients whose TNF level was elevated at seven days had a 20 point lower survival rate: 62 percent were alive after a year, compared with 85 percent of those patients with a lower TNF level.

Dr. Levine says the research is one small step in a long road to making transplants safer and more effective.

Study author Carrie Kitko, M.D., a pediatric fellow at the U-M Health System, says 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 and she says they are currently conducting a clinical trial using one of these drugs, etanercept, in clinical trials to see if it can prevent or treat GVHD.

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

Apparently 40 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 www.cancer.med.umich.edu/clinic/bmtclinic.htm or call the Cancer AnswerLine at 800-865-1125.