Chemotherapy Benefits Subset of Childhood ALL Induction Failures

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(ChemotherapyAdvisor) – A subset of pediatric patients with acute lymphoblastic leukemia (ALL) who have precursor B-cell leukemia appear to have a better outcome with chemotherapy after failing remission-induction therapy, results of the largest study in this population reported in the New England Journal of Medicine April 12.

“Induction failure is rare, occurring in only 2% to 3% of all patients, but it constitutes one of the most unfavorable outcomes in pediatric ALL,” the investigators wrote. “…our analysis showed no benefit of allogeneic transplantation in patients younger than 6 years of age who had precursor B-cell ALL and induction failure and no high-risk cytogenetic features ― an observation with considerable clinical implications, since transplantation is generally considered to be the standard of care for such patients.”

Investigators identified induction failure in 1,041 of 44,017 patients (2.4%) who were aged 0–18 years with newly diagnosed ALL treated by 14 cooperative study groups in the U.S., Europe, and Asia between 1985 and 2000. Induction failure was defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4–6 weeks of remission-induction therapy. Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement.

Median follow-up was 8.3 years (range, 1.5 to 22.1). The ten-year survival rate (±SE) was estimated at 32±1%. Particularly poor outcomes were observed in patients ages 10 years or older, those with T-cell leukemia, presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy.

In patients with precursor B-cell leukemia, factors associated with a favorable outcome were high hyperdiploidy (a modal chromosome number >50) and an age of 1–5 years. Children <6 years of age with precursor B-cell leukemia and no adverse genetic features had a ten-year survival rate of 72±5% when treated with chemotherapy only. In those with T-cell leukemia, allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes.

“Pediatric ALL with induction failure is highly heterogeneous,” they concluded. “Patients who have T-cell leukemia appear to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients who have precursor B-cell leukemia without other adverse features appear to have a better outcome with chemotherapy.”

Abstract

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