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Fred Hutchinson Cancer Research Center Found that Marrow Transplantation Using an Unrelated Donor Should be Considered for Children with Acute Leukemia

SEATTLE — Mar. 20, 2002 — Researchers demonstrate that bone-marrow transplantation between tissue-matched, unrelated individuals is a viable option for young children with acute lymphoblastic leukemia (ALL), the most common form of childhood cancer.

According to a recent study led by Dr. Ann Woolfrey, a pediatric oncologist at the Fred Hutchinson Cancer Research Center, 70 percent of children under age 18 diagnosed with very high risk leukemia and who received transplants while in their first remission were leukemia-free three years after treatment. Outcome was particularly favorable for children under age 10. Results from the study appeared in the March 15 issue of Blood.

"The best news from our study is that transplants with unrelated donors can be as successful as transplants with related donors for treatment of children with ALL," says Woolfrey. "This means that doctors should have no hesitation about referring a child with ALL for a bone-marrow transplant if they have no tissue-matched relative. For younger patients, this allows us to be more aggressive in terms of accepting patients for transplant rather than continuing to treat them with less effective chemotherapy."

The study aimed at identifying factors associated with outcomes for patients who underwent an unrelated donor transplant. While phase of disease is the strongest factor in determining a patient's potential for survival, age and duration of the patient's remission were significant.

"What's unique in our study was the ability to tease out the specific factors that are important for outcome," says Woolfrey. "This information now helps us to decide which patients should be considered for transplant and to identify areas in which we can improve the procedure for higher risk patients."

Patients with ALL are typically first treated with intensive chemotherapy to induce remission. Those who respond favorably to such therapy are then treated with conventional chemotherapy, while patients who do not respond or who have characteristics predictive of poor outcome are considered candidates for bone-marrow transplantation, as are patients who relapse after one cycle of chemotherapy. Other poor prognostic indicators include genetic abnormalities such as the Philadelphia chromosome, in which two chromosomes break and portions of each are swapped, and a defect in a gene known as MLL, for mixed-lineage leukemia.

During the study, the researchers followed the outcomes of 88 ALL patients under age 18 who received unrelated donor bone-marrow transplants at Fred Hutchinson between 1987 and 1999. Three years after transplant the leukemia-free survival rates, according to phase of disease at transplantation, were 70 percent, 46 percent, 20 percent and 9 percent, respectively, for patients in first remission, second remission, third remission and relapse.

A first remission of two years or longer was highly predictive of survival after transplant. Previously, the duration of first remission was thought only to predict outcome of conventional chemotherapy.

For patients in second remission who were younger than 10 years at transplantation, the leukemia-free survival rate at three years was 61 percent, indicating that age has a significant impact on transplant outcome.

The improved survival of younger patients was due entirely to fewer deaths from causes other than relapse, such as infection and graft-vs.-host disease.

"We saw no differences in relapse rates among age groups, and our study indicated that younger patients suffered fewer life-threatening complications from the transplant procedure which accounted for the survival difference," says Woolfrey. Although the study is most encouraging for younger children, the findings will impact the approach taken with older patients as well."

According to Woolfrey, also an assistant professor of pediatrics at the University of Washington, these results will help to explore ways to lessen transplant mortality in the older age children. For example, such children might benefit from transplants with peripheral blood stem cells, which have been shown in studies to be highly effective for adult patients who have advanced beyond first remission.

Media Contact
Susan Edmonds
(206) 667-2896
sedmonds@fhcrc.org

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Fred Hutchinson Cancer Research Center
The Fred Hutchinson Cancer Research Center, home of two Nobel Prize laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical and research partners, the University of Washington Academic Medical Center and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 38 nationwide. For more information, visit the center's Web site at www.fhcrc.org.