Failure of remission-induction therapy in pediatric acute lymphoblastic leukemia (ALL), although rare, can lead to highly adverse outcomes, but outcomes differ according to type of ALL: B-cell or T-cell, as well as other characteristics (Schrapps M, et al. N Engl J Med. 2012;366:1371-1381).
The study showed that patients with childhood ALL who fail on induction therapy are highly heterogeneous. T-cell leukemia appears to be associated with improved outcomes if treated with allogeneic stem-cell transplant, while precursor B-cell leukemia with no adverse features appears to be better treated with chemotherapy.
According to the authors, “These findings have considerable implications, since transplantation is generally considered to be standard of care for such patients.”
The study was based on 1041 children and adolescents (aged 0-18 years) with newly diagnosed ALL who experienced failure after 4 to 6 weeks of remission-induction therapy; these children were culled from 44,017 patients with childhood ALL treated by 14 cooperative study groups between 1985 and 2000.
Patients with induction failure tended to have high-risk features that included older age, high leukocyte count, T-cell leukemia phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up of 8.3 years, the 10-year survival rate was 32%.
Characteristics associated with a particularly poor outcome included age of 10 years or more, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy. Improved outcomes in precursor B-cell ALL were associated with high hyperdiploidy (a modal chromosome number >50) and age of 1 to 5 years; these patients composed about 25% of the sample.
Improved outcomes in T-cell ALL were seen with allogeneic stem-cell transplant from matched, related donors. Children younger than 6 years with precursor B-cell ALL and no adverse genetic features had a 10-year survival rate of 72% when treated with chemotherapy only.