title: Six months of maintenance chemotherapy after intensified treatment for acute lymphoblastic leukemia of childhood.
abstract: OBJECTIVE
  We postulated that intensification of chemotherapy immediately after remission induction might reduce the leukemic cell burden sufficiently to allow an abbreviated period of antimetabolite therapy.
  
  
  METHODS
  Three hundred forty-seven children (ages 1 to 15 years) with previously untreated acute lymphoblastic leukemia (ALL) were enrolled onto the Tokyo L92-13 study, which excluded patients with mature B-cell ALL and patients less than 1 year old. One hundred twenty-four patients were classified as standard risk, 122 as high risk, and 101 as extremely high risk, according to age, peripheral-blood leukocyte count, selected genetic abnormalities, and immunophenotype. All subjects received four drugs for remission induction, followed by a risk-directed multidrug intensification phase and therapy for presymptomatic leukemia in the CNS. Maintenance chemotherapy with oral mercaptopurine and methotrexate was administered for 6 months, with all treatment stopped by 1 year after diagnosis.
  
  
  RESULTS
  The mean (+/- SD) event-free survival (EFS) and overall survival rates for all patients were 59.5% +/- 3.4% and 81.5% +/- 2.2%, respectively, at 5. 5 years after diagnosis. EFS rates by risk category were similar (60. 2% +/- 6.0% for standard risk, 57.7% +/- 5.6% for high risk, and 62. 5% +/- 5.7% for extremely high risk), whereas overall survival rates differed significantly (91.2% +/- 2.7%, 80.0% +/- 4.1%, and 72.1% +/- 4.5%, respectively, P <.0001 by the log-rank test). There were 107 relapses. Eighty-five (79.4%) of these 107 patients achieved second complete remissions, with subsequent EFS rates of 61.5% +/- 7. 9% (standard risk), 42.6% +/- 8.1% (high risk), and 9.6% +/- 6.4% (extremely high risk). Of the five risk factors analyzed, only the response to prednisolone monotherapy among extremely high-risk patients proved important.
  
  
  CONCLUSIONS
  Early treatment intensification did not compensate for a truncated phase of maintenance chemotherapy in children with standard- or high-risk ALL. However, 6 months of antimetabolite treatment seemed adequate for extremely high-risk patients who were good responders to prednisolone and received intensified chemotherapy that included high-dose cytarabine early in the clinical course.
authors.affiliation: Department of Oncology, Kanagawa Children's Medical Center, and Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Toyoda
authors.forename: A
authors.initials: A
authors.lastname: Manabe
authors.forename: M
authors.initials: M
authors.lastname: Tsuchida
authors.forename: R
authors.initials: R
authors.lastname: Hanada
authors.forename: K
authors.initials: K
authors.lastname: Ikuta
authors.forename: Y
authors.initials: Y
authors.lastname: Okimoto
authors.forename: A
authors.initials: A
authors.lastname: Ohara
authors.forename: Y
authors.initials: Y
authors.lastname: Ohkawa
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Ishimoto
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Kaneko
authors.forename: M
authors.initials: M
authors.lastname: Maeda
authors.forename: K i
authors.initials: Ki
authors.lastname: Koike
authors.forename: T
authors.initials: T
authors.lastname: Shitara
authors.forename: Y
authors.initials: Y
authors.lastname: Hoshi
authors.forename: R
authors.initials: R
authors.lastname: Hosoya
authors.forename: Y
authors.initials: Y
authors.lastname: Tsunematsu
authors.forename: F
authors.initials: F
authors.lastname: Bessho
authors.forename: S
authors.initials: S
authors.lastname: Nakazawa
authors.forename: T
authors.initials: T
authors.lastname: Saito
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002051:Burkitt Lymphoma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D015122:Mercaptopurine; D008727:Methotrexate