Transplants ALL the way

Procedure works to fight most common childhood cancer in cases without related donors, says study by Woolfrey
Dr. Ann Woolfrey with pediatric patient.
Dr. Ann Woolfrey consults with Leanne Looney and her 21/2-year-old daughter Alyson. Photo by Gordon Todd

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.

A recent study by the Clinical Research Division shows that 70 percent of children diagnosed with high-risk leukemia who received transplants while in their first remission were leukemia-free three years after treatment. Outcome was particularly favorable among the youngest.

The largest single-institution analysis of its kind, the study suggests that transplantation should be considered for children with ALL who have no tissue-matched relatives as potential bone-marrow donors, said Dr. Ann Woolfrey, lead author of the study, which appears 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," she said.

'No hesitation'

"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."

Woolfrey, also an assistant professor of pediatrics at the University of Washington, said previous studies focused exclusively on survival rates of children who have undergone marrow transplantation for treatment of ALL.

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

Patients with ALL typically are 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 that predict poor outcome are considered candidates for bone-marrow transplantation, as are patients who relapse after remission induction.

Poor 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.

88 pediatric ALL patients

The researchers followed the outcomes of 88 ALL patients under 18 who received unrelated-donor bone-marrow transplants at the Center between 1987 and 1999.

At three years post-transplant, 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, second and 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-versus-host disease, Woolfrey said.

"We saw no differences in relapse rates among age groups," she said. "Our study indicated that younger patients suffered fewer life-threatening complications from the transplant procedure, which accounted for the survival differences."

Although the study is most encouraging for younger children, Woolfrey said the findings will impact the approach taken with older patients as well.

"These results will help us to explore ways to lessen transplant mortality in the older children," she said. "For example, such children might benefit from transplants with peripheral-blood stem cells, which have been shown in studies led by (Dr.) Bill Bensinger to be highly effective for adult patients who have advanced beyond first remission."



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