More chemotherapy might be best move for some children with leukemia

Following failure of induction therapy, some children with acute lymphoblastic leukemia (ALL) appear to have a better outcome with additional chemotherapy than with allogeneic stem cell transplantation, a large, long-term study has revealed.

Investigators evaluated the outcomes of 44,017 patients with ALL aged 17 years and younger who had been diagnosed during a 15-year period ending in December 2000. Each child had undergone treatment through a clinical trial at one of the centers participating in this international collaborative analysis. Induction failure was defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy.

A total of 1,041 (2.4%) of the patients experienced induction failure. With a median follow-up period of 8.3 years (range: 1.5 to 22.1 years), the 10-year survival rate for such children was estimated at only 32.1%.

Many of the children who experienced induction failure presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. Patients aged 10 years and older, patients with T-cell leukemia, the presence of an 11q23 rearrangement, and patients with 25% or more blasts in the bone marrow at the end of induction therapy had particularly poor outcomes. However, allogeneic stem cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia.

Among children younger than age 6 years with precursor B-cell leukemia and no adverse genetic features who underwent additional chemotherapy only, the 10-year survival rate was 72.5%.

“These results tell us that induction failure should no longer be considered an automatic indication for a [bone marrow] transplant,” explained study coauthor Ching-Hon Pui, MD, chair of the St. Jude Children's Research Hospital Department of Oncology in Memphis, Tennessee, in a statement announcing the publication of the study results in The New England Journal of Medicine (2012;366:1371-1381).

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