title: 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.).
authors.affiliation: Department of Pediatrics, University Medical Center Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Vaskar
authors.initials: V
authors.lastname: Saha
authors.forename: Paul S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
authors.forename: Jacques
authors.initials: J
authors.lastname: Otten
authors.forename: Akira
authors.initials: A
authors.lastname: Ohara
authors.forename: Anne Birgitta
authors.initials: AB
authors.lastname: Versluys
authors.forename: Gabriele
authors.initials: G
authors.lastname: Escherich
authors.forename: Mats
authors.initials: M
authors.lastname: Heyman
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Camitta
authors.forename: Jochen
authors.initials: J
authors.lastname: Harbott
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Riehm
authors.forename: Sue
authors.initials: S
authors.lastname: Richards
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016044:Fusion Proteins, bcr-abl