title: Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: the AML99 trial from the Japanese Childhood AML Cooperative Study Group.
abstract: OBJECTIVE
  To improve the prognosis in children with newly diagnosed acute myeloid leukemia (AML) by introducing a dose-dense intensive chemotherapy regimen and an appropriate risk stratification system.
  
  
  METHODS
  Two hundred forty children with de novo AML were treated with continuous cytarabine-based induction therapy and stratified to three risk groups based on the initial treatment response, age, and WBC at diagnosis and cytogenetics. All of the patients were treated with intensive consolidation chemotherapy including three or four courses of high-dose cytarabine. Allogeneic hematopoietic stem-cell transplantation (HSCT) was indicated for only the intermediate-risk patients with matched related donors and for all the high-risk subsets.
  
  
  RESULTS
  Two hundred twenty-seven children (94.6%) achieved a complete remission (CR). Four children demonstrated induction death. The median follow-up of the live patients was 55 months (range, 37 to 73 months). The 5-year overall survival of all 240 children was 75.6% (95% CI, 70.3% to 81.4%) and event-free survival was 61.6% (95% CI, 55.8% to 68.1%). The 5-year disease-free survival in each risk group were 71.3% (95% CI, 63.4% to 80.2%) in the low-risk group (n = 112), 59.8% (95% CI, 50.6% to 70.7%) in the intermediate-risk group (n = 92), and 56.5% (95% CI, 39.5% to 80.9%) in the high-risk group (n = 23). Eight children died during the first CR, including four after HSCT.
  
  
  CONCLUSIONS
  A high survival rate, 75.6% at 5 years, was achieved for childhood with de novo AML in the AML99 trial. The treatment strategy was well tolerated with only 1.7% induction death rate and 3.5% remission death rate. Low-risk children were successfully treated with chemotherapy alone.
authors.affiliation: Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tsukimoto
authors.forename: Akio
authors.initials: A
authors.lastname: Tawa
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.forename: Ken
authors.initials: K
authors.lastname: Tabuchi
authors.forename: Hisato
authors.initials: H
authors.lastname: Kigasawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchida
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yabe
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Kazuko
authors.initials: K
authors.lastname: Hamamoto
authors.forename: Masue
authors.initials: M
authors.lastname: Imaizumi
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hanada
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D014184:Transplantation, Homologous
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine