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.

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 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 versus 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 versus 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 versus 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 versus 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, at the U-M Medical School.

Research led by James Ferrara, director of the Blood and Marrow Transplantation Program at the U-M Comprehensive Cancer Center has previously linked TNF to graft versus 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 ( Enbrel ), in clinical trials to see if it can prevent or treat GVHD, " says study author Carrie Kitko, 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.

Source: University of Michigan Health System, 2006


XagenaMedicine2006