title: High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia. Results of protocol ALL VI from the Dutch Childhood Leukemia Study Group.
abstract: OBJECTIVE
  Here we report the results of a nationwide cooperative study in the Netherlands on acute lymphoblastic leukemia (ALL) in children. The aim of the study was to improve the cure rate and to minimize side effects in a group of non-high-risk ALL patients, especially with regard to the CNS. A second aim was to study potential prognostic factors.
  
  
  METHODS
  Children (age 0 to 15 years) with non-high-risk ALL (WBC count < 50 x 10(9)/L, no mediastinal mass, no B-cell phenotype, and no CNS involvement) were treated with a uniform protocol, ALL VI. The treatment protocol used 6-week induction regimen with three drugs (vincristine, dexamethasone, and asparaginase), three weekly doses of intravenous (IV) medium high-dose methotrexate (2 g/m2), and 2-year maintenance therapy that consisted of alternating 5-week periods of methotrexate and mercaptopurine and 2-week periods of vincristine and dexamethasone. In the first year of maintenance, triple intrathecal therapy was administered every 7 weeks.
  
  
  RESULTS
  From December 1, 1984 until July 1, 1988, 291 children with ALL were diagnosed; 206 were categorized as non-high-risk (71%), and 190 were treated according to protocol ALL VI. At 8 years, the event-free survival (EFS) rate was 81% (SE = 3%) and survival rate 85% (SE = 2.9%); the median follow-up time was 7.3 years (range, 36 to 117 months). The CNS relapse rate was 1.1% (two of 184 patients who achieved a complete remission [CR]). The only factor found to be of negative prognostic importance in terms of EFS (P = .05) was a positive acid phosphatase reaction.
  
  
  CONCLUSIONS
  For children with non-high-risk ALL, the combination of IV medium high-dose methotrexate (2 g/m2 times three), triple intrathecal therapy in the first year of maintenance treatment, and the use of dexamethasone for induction and pulses during maintenance treatment has proved to be highly effective, especially in the prevention of CNS relapse. A high cure rate was achieved without the use of anthracyclines, alkylating agents, and cranial irradiation.
authors.affiliation: Dutch Childhood Leukemia Study Group, Hague, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Veerman
authors.forename: K
authors.initials: K
authors.lastname: Hählen
authors.forename: W A
authors.initials: WA
authors.lastname: Kamps
authors.forename: E F
authors.initials: EF
authors.lastname: Van Leeuwen
authors.forename: G A
authors.initials: GA
authors.lastname: De Vaan
authors.forename: G
authors.initials: G
authors.lastname: Solbu
authors.forename: S
authors.initials: S
authors.lastname: Suciu
authors.forename: E R
authors.initials: ER
authors.lastname: Van Wering
authors.forename: A
authors.initials: A
authors.lastname: Van der Does-Van der Berg
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009426:Netherlands; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D008727:Methotrexate