Induction failure in ALL is associated with clinical and biologic heterogeneity.

  • Major finding: Induction failure in ALL is associated with clinical and biologic heterogeneity.

  • Approach: Retrospective analysis was performed on patients from 14 study groups.

  • Impact: The current standard of care may not benefit all patients who fail induction.

Current treatment regimens cure approximately 80% of children diagnosed with acute lymphoblastic leukemia (ALL). However, for those rare patients who do not achieve a complete remission after induction chemotherapy, the prognosis tends to be poor, and these patients are uniformly offered allogeneic hematopoietic stem-cell transplantation. Schrappe and colleagues performed a retrospective analysis of 44,017 pediatric patients diagnosed with ALL from 1985 through 2000 and discovered that clinical, biologic, and prognostic heterogeneity were associated with induction failure. A total of 1,041 patients (2.4%) failed induction therapy, with an overall 10-year survival rate of 32%. The authors found that the high-risk features generally associated with a diagnosis of ALL were overrepresented in this cohort, including older age, high leukocyte count, T-cell disease, male sex, Philadelphia chromosome positivity, and MLL rearrangement. Interestingly, within this poor prognosis group, patients with certain biologic features, such as high hyperdiploidy and younger age, had a significantly better rate of survival. In contrast, older age, T-cell disease, and MLL rearrangement were associated with a particularly poor outcome. The treatments administered to these patients also affected their prognosis and clinical outcome. Specifically, patients with T-cell leukemia fared better when they were treated with allogeneic stem-cell transplantation, whereas younger patients with precursor B-cell leukemia who received chemotherapy showed the best overall 10-year survival rate. These findings therefore suggest that stem-cell transplantation may not benefit all patients who fail induction chemotherapy. Rather, specific disease features may be used to personalize therapy and improve outcomes in patients with ALL.

Schrappe M, Hunger SP, Pui CH, Saha V, Gaynon PS, Baruchel A, et al. Outcomes after induction failure in childhood acute lymphoblastic leukemia. N Engl J Med 2012;366:1371–81.

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