Outcomes after induction failure in childhood acute lymphoblastic leukemia

Abstract

Background: Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL).

Methods: We identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients.

Results: 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. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (±SE) was estimated at only 32±1%. An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy (a modal chromosome number >50) and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia. Allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia. Children younger than 6 years of age with precursor B-cell leukemia and no adverse genetic features had a 10-year survival rate of 72±5% when treated with chemotherapy only.

Conclusions: Pediatric ALL with induction failure is highly heterogeneous. 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. (Funded by Deutsche Krebshilfe and others.).

Figure 1. Kaplan–Meier Analysis of Survival in the 624 Study Patients with Induction Failure Who Had Genetic Data, According to Genetic Abnormality

Ten-year survival estimates (±SE) are shown, along with the total numbers of patients with data and the total numbers of deaths. MLL denotes the mixed-lineage leukemia gene.

Figure 2. Estimates of Overall Survival in Patients with Induction Failure, According to Treatment

Ten-year survival estimates (±SE) are shown, along with the total numbers of patients with data and the total numbers of deaths. Only data from patients who survived at least 6 months are included. Overall survival is shown for patients with precursor B-cell leukemia (without a rearranged mixed-lineage leukemia gene [MLL]) who were younger than 6 years of age (Panel A) and who were 6 years of age or older (Panel B). Also shown is the overall survival among patients with T-cell leukemia (Panel C). SCT denotes stem-cell transplantation.