New Treatments Fight GVHD In Bone Marrow Transplant Patients

It's hard to imagine your body being attacked by foreign blood cells while your own immune system is unable to defend you. Unfortunately, for many bone marrow transplant patients, graft versus host disease (GVHD) is a common and often deadly complication of this life-saving procedure.

However, research by the University of Michigan Comprehensive Cancer Center has revealed a new way to fight back against these attacks.

"When graft versus host disease occurs, it can be fatal in about 50 percent of the cases," says James Ferrara, M.D., director of the Blood & Marrow Transplantation Program at the U-M Comprehensive Cancer Center. "Through our research, we've found some of the reasons behind graft versus host involve an inflammatory reaction, and treating the inflammatory reaction may curb graft versus host."

More than 5,000 Americans receive allogeneic bone marrow transplants annually, meaning the bone marrow donor is someone other than the patient or his identical twin.

GVHD occurs when cells from the donated bone marrow attack the body of the transplant patient, whose own immune system has been repressed in order to allow the new bone marrow to grow. Most often, it is the skin, eyes, stomach, and intestines that are affected.

Ferrara and his colleagues have found that as this immune system reaction progresses, it mimics a very large inflammation in the body, and that specific proteins are directly responsible for this inflammation.

"There are certain antidotes to these proteins. Knowing that, we have developed new trials both to treat GVHD, as well as to prevent it," Ferarra explains.

Graft versus host disease is normally treated using high dose steroids, but only about a third of the patients respond to this treatment. However, using anti-inflammatory proteins in combination with steroids has yielded a response rate of over two-thirds, twice the traditional rate of complete response.

The researchers are particularly excited about the use of etanercept, a drug that is commonly used to reduce the inflammation of rheumatoid arthritis, to treat GVHD. "The treatment is very simple. It's a shot, similar to an insulin injection, that is given twice a week," says Ferarra.

The new treatments reduce the risk of death, hospitalization and serious side effects associated with bone marrow transplants and GVHD. This means that patients who get transplants will have a much higher chance of being cured without the debilitating effects of GVHD, and also that bone marrow transplant is likely to become more available to patients who need it.

GVHD is much more intense in older patients, which has been a problem since most of the people who need bone marrow transplants are over the age of 50. "With this new approach we are now likely to be able to offer bone marrow transplants to the very people who need them, the more elderly populations who are at risk and who could benefit from transplants as a therapy," Dr. Ferarra says.

There are currently two to three times as many patients who need bone marrow transplants than those who actually receive them, mostly due to the intense risks of GVHD. In addition to older populations, now patients who have non-malignant diseases such as scleroderma, an auto immune disease, or other toxic but not necessarily life threatening diseases can have the option of a transplant.

A bone marrow transplant occurs when defective or cancerous bone marrow is replaced with healthy marrow, either from the patient or a donor. Transplants are used most commonly for cancers of the blood, such as lymphomas and leukemia, or to correct certain genetic diseases, defects in the immune system, or other problems in the blood cells.

It is still important that the donor and the transplant recipient have as close a match as possible, and Ferarra encourages everyone to do his or her part by becoming a donor. Today, new advances have made bone marrow donation similar to donating a pint of blood.

"It is very easy for anonymous donors to provide their stem cells. We now have millions of patients in registries, and we are looking for even more so that we can have perfect matches for everyone who might need a bone marrow transplant," he says.

For more information, visit these Web sites:

U-M Comprehensive Cancer Center: BMT patient guide http://www.cancer.med.umich.edu/cancertreat/treatment/bmt/complications.shtml

U-M Blood & Marrow Transplantation Program http://www.cancer.med.umich.edu/cancertreat/treatment/bmt/about_the_program.shtml

National Marrow Donor Program
http://www.marrow.org

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