Oct. 30, 2003 Washington, D.C. – Georgetown University Medical Center researcher Carolyn Hurley, Ph.D. and colleagues have developed new comprehensive national guidelines on bone marrow transplantation that involve donors unrelated to the patient. The guidelines, which encourage transplant physicians to develop robust donor search strategies, have been issued by the National Marrow Donor Program and appear as a commentary in the current issue of the journal Biology of Blood and Marrow Transplantation.
Every year, thousands of Americans with leukemia, genetic disorders like Fanconi Anemia, and other potentially fatal blood diseases need a marrow transplant. For 70% of these individuals, sibling donors – who have a 1 in 4 chance of having marrow matching that of the patient – are not available and an unrelated donor is the only hope.
The major criteria for marrow donor matching is a set of genetically determined molecules known as histocompatibility antigens (HLA) which determine whether donated marrow is accepted or rejected by the immune system. "By matching as closely as possible donor HLA molecules to those of the recipient we are trying to fool the immune system so it thinks the bone marrow graft is not foreign," said Hurley, professor of oncology at Georgetown's Lombardi Comprehensive Cancer Center.
Any healthy individual can be a bone marrow donor as donated marrow is quickly replaced by the body. Over 5 million Americans have placed their names on the National Marrow Donor Program registry indicating willingness to be an unrelated marrow donor. "The closer the HLA molecules of a potential donor and recipient match the fewer medical problems the recipient will have," said Dr. Hurley. For this reason the new guidelines call for searches within the registry to be conducted by histocompatibility specialists and for patients to be HLA typed to a high degree of resolution.
To describe the search for HLA compatible donors on the registry, Hurley uses the analogy of searching for a specific individual in a city of 5 million. "First you identify all the people with the same surname, say 'Doe'. That's a very large group but it does include the person you need, you just can't find the one you seek within the crowd. But if you go to a higher degree of resolution and cull out all those named Mary Doe, you can narrow your search considerably. But that's not specific enough, so you go to yet a higher degree of resolution and have the computer spit out all the Mary Margaret Does."
Dr. Hurley notes that due to cost considerations, the volunteer donors listed on the registry are labeled only to the Mary Doe specificity level. Donor selection specialists select from these individuals to determine which ones to test to find Mary Margaret Does or even the Mary Margaret Does born in the fifth decade of the 20th century.
High resolution HLA typing needs to be done for all transplant patients, Dr. Hurley said, although it is too costly to conduct high resolution testing on all volunteer donors listed on the registry. And since the patients are sick and can go downhill rapidly, it is important to find the best donor quickly. That's why the guidelines call for a specialist to conduct the search, rapidly narrowing the likely potential donors to those with the highest likelihood of matching for which high resolution testing can be done.
The guidelines encourage consideration of transplants as a treatment option even without a perfect match. "While the best results are obtained with HLA matches, the new guidelines indicate to transplant physicians that they can get good results with some degree of HLA molecule mismatching although the final word is not in on how mismatched the donor and recipient can be.
The physician must compare the risks of a transplant with the best available mismatched donor to the risks of other treatment to make the best decision for the patient. With these practical guidelines, the NMDP conveys to transplant physicians a roadmap to help them make informed decisions about how to treat patients for whom an exact match cannot be found," said Dr. Hurley.
Dr. Hurley, who is engaged in research on the genetics underlying HLA compatibility, chairs the Histocompatibility Committee that advises the National Marrow Donor Program on search and match issues and is Vice President (representing the Americas) of the World Marrow Donor Association.
Coauthors of the guidelines are Lee Ann Baxter Lowe, Ph.D. of the University of California in San Francisco, Brent Logan, Ph.D. of the Medical College of Wisconsin, Chatchada Karanes, M.D. of the National Marrow Donor Program, Claudio Anasetti, M.D. of the Fred Hutchinson Cancer Research Center, Daniel Weisdorf, M.D. of the National Marrow Donor Program and the University of Minnesota and Dennis L. Confer of the National Marrow Donor Program.
The Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future.
Lombardi is one of only 39 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington DC area. For more information, go to http://www.georgetown.edu/gumc.
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