Outcomes after induction failure in childhood acute lymphoblastic leukemia.

Journal article

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.).

Authors: Schrappe, M; Hunger, S; Pui, C; Saha, V; Gaynon, P

• Publication status: Published
• Journal: New England journal of medicine
• Volume: 366
• Issue: 15
• Pages: 1371-1381
• Publication date: 2012-04-01
• DOI: 10.1056/nejmoa1110169
• EISSN: 1533-4406
• ISSN: 0028-4793
• Language: English
• Keywords: Treatment Outcome; Retrospective Studies; Adolescent; Treatment Failure; Follow-Up Studies; Stem Cell Transplantation; Prognosis; Child; Leukocyte Count; Survival Rate; Humans; Age Factors; Female; Fusion Proteins, bcr-abl; Male; Kaplan-Meier Estimate; Child, Preschool; Infant; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Gene Rearrangement; Remission Induction; Antineoplastic Agents