Marrow transplant side effect

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Study finds new cause for marrow transplant side effect Source: (cancerfacts.com) Tuesday, June 04, 2002 ANN ARBOR, Mich. -- June 4, 2002 -- Scientists reported this week that they have discovered how graft-versus-host disease, a common and deadly complication of life-saving bone marrow transplants, attacks and often kills its victims. Contrary to current understanding of graft-versus-host-disease (GVHD) the study shows how skin, liver and gastrointestinal cells in mice with GVHD are destroyed from a distance by a firestorm of immune system proteins called inflammatory cytokines. The research team led by Dr. James Ferrara, published the findings in the June 2002 issue of Nature Medicine. Ferrara says the results call into question a widely accepted assumption that T cells – immune cells which attack and kill just one target cell at a time – are the major cell-killing agents of graft-versus-host disease. “Cytokines turn healthy immune cells in donated bone marrow – something given to cure patients -- into lethal weapons capable of killing them,” says Ferrara, director of the UM Bone Marrow Transplantation Program. “Now that we know cytokines are the major cause of GVHD-induced cell damage, we can look for ways to neutralize them or block their production,” Graft versus host disease arises when the immune system that grows from the transplanted donor marrow recognizes the patient’s tissues as foreign and mounts an immune system attack on them. It is the opposite of organ rejection in patients who receive a donor organ, where the patient’s immune system attacks the donor organ. The UM discovery could help prevent the 500 deaths and reduce the risk of hospitalization and debilitating side-effects that can affect the more than 5,000 Americans who receive donor bone marrow transplants annually, primarily to treat leukemia and other cancers. The study’s findings will help scientists focus GVHD prevention strategies on its primary killing agents – especially two powerful cytokines called tumor necrosis factor-alpha and interleukin-1, Ferrara says. The risk of graft-versus-host disease is highest following a bone marrow transplant from an allogeneic donor – someone other than the patient or the patient’s identical twin. Symptoms of acute GVHD usually begin three to six weeks after the transplant, often after the patient has been discharged and appears to be recovering well. In clinical trials under way at the U-M Cancer Center, Ferrara and colleagues are investigating new drugs that bind to and neutralize tumor necrosis factor. The researchers are testing these drugs to determine if they can prevent cell damage in patients with GVHD and lung disease after a bone marrow transplant. In a future study, Ferrara hopes to determine whether other drugs can block the original interaction between host and donor immune cells, preventing the initial activation phase of acute GVHD. Copyright ?2001 NexCura, Inc. All rights reserved. Republication or redistribution of cancerfacts.com content, including by framing or similar means, is expressly prohibited without the prior written consent of NexCura. NexCura and cancerfacts.com are trademarks of NexCura, Inc. or its affiliates. Copyright ?2001. This information is for educational purposes only.