A subset of young patients with acute lymphoblastic leukemia (ALL) who fail to achieve remission after the initial weeks of intense chemotherapy known as induction therapy appear to have better outcomes with additional chemotherapy rather than bone marrow transplantation, according to the results of an international study published in the New England Journal of Medicine.
ALL—a fast-growing cancer of the white blood cells—is the most commonly diagnosed type of leukemia in children. Each year, there are approximately 6,000 new cases of ALL diagnosed in the United States.
The treatment of childhood ALL is carried out in two phases. The initial treatment phase is called remission induction and its goal is to achieve a complete remission or disappearance of all detectable leukemia cells in the peripheral blood and bone marrow. After a complete remission is achieved, the second phase of treatment, called post-remission therapy, begins. Post-remission therapy is necessary because despite achieving a complete remission of leukemia with induction treatment, hidden undetectable leukemia cells still exist and the leukemia will return without additional post-remission therapy.
Induction failure is rare, but children who do fail induction are at a very high risk for poor outcomes. The overall long-term survival rate for childhood ALL patients is 80 percent, but that rate plummets to 32 percent for patients who fail induction. They are sometimes treated with bone marrow transplants, but this may not always be the best course of action according to the new data.
This international study included a total of 14 cooperative study groups in the U.S., Europe, and Asia. It was the largest study ever of pediatric ALL patients, involving 44,017 patients ages 0 to 18 with newly diagnosed ALL who were treated between 1985 and 2000. The researchers identified 1,041 patients (2.4%) whose cancer did not go into remission after four to six weeks of induction therapy and then analyzed the relationships among disease characteristics and outcomes in these patients.
They identified a subset of young patients who achieved 10-year survival rates of 72 percent after additional chemotherapy rather than bone marrow transplantation. These patients had B-cell leukemia, were between the ages of 1 and 5 when their cancer was diagnosed, and many had more than 50 chromosomes in their leukemia cells, rather than the normal number of 46 chromosomes. They also had no other markers of high risk, including high white blood cell counts or chromosomal rearrangements involving the MLL gene.
In contrast, the researchers found that transplants are still the best hope for some other young ALL patients who fail induction therapy—namely those with T-cell leukemia, which accounts for 12 to 15 percent of childhood ALL.
The bottom line—one size does not fit all when it comes to treating childhood ALL. The researchers concluded that patients with T-cell leukemia appear to have better outcomes with allogeneic stem cell transplantation than with chemotherapy, whereas patients with B-cell leukemia without other adverse features appear to have better outcomes with chemotherapy.
The researchers concluded that bone marrow transplantation should not be an automatic response to induction failure—instead, physicians should be aware that some patients will benefit from additional chemotherapy.
 Schrappe M, Hunger SP, Pui CH, et al. Outcomes after induction failure in childhood acute lymphoblastic leukemia. New England Journal of Medicine. 2012; 366:1371-1381.
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