title: Key treatment questions in childhood acute lymphoblastic leukemia: results in 5 consecutive trials performed by the ALL-BFM study group from 1981 to 2000.
abstract: Between 1981 and 2000, 6 609 children (<18 years of age) were treated in 5 consecutive trials of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria, and Switzerland. Probability of 10-year event-free survival (survival) improved from 65% (77%) in study ALL-BFM 81-78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: 1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk ALL patients and eliminated in non-high-risk non-T-ALL patients, if it was replaced by high-dose and intrathecal methotrexate; 2) omission of delayed reintensification severely impaired outcome of low-risk patients; 3) 6 months less maintenance therapy caused an increase in systemic relapses; 4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; 5) condensed induction therapy resulted in a significant improvement of outcome; 6) the daunorubicin dose in induction could be safely reduced in low-risk patients; 7) intensification of consolidation/reintensification treatment led to considerable improvement of outcome in high-risk patients.
authors.affiliation: Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. m.schrappe@pediatrics.unikiel.de
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: A
authors.initials: A
authors.lastname: Möricke
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.forename: G
authors.initials: G
authors.lastname: Henze
authors.forename: K
authors.initials: K
authors.lastname: Welte
authors.forename: H
authors.initials: H
authors.lastname: Gadner
authors.forename: W-D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: J
authors.initials: J
authors.lastname: Ritter
authors.forename: J
authors.initials: J
authors.lastname: Harbott
authors.forename: G
authors.initials: G
authors.lastname: Mann
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.forename: B
authors.initials: B
authors.lastname: Gruhn
authors.forename: C
authors.initials: C
authors.lastname: Niemeyer
authors.forename: B
authors.initials: B
authors.lastname: Kremens
authors.forename: F
authors.initials: F
authors.lastname: Niggli
authors.forename: K-M
authors.initials: KM
authors.lastname: Debatin
authors.forename: R
authors.initials: R
authors.lastname: Ratei
authors.forename: M
authors.initials: M
authors.lastname: Stanulla
authors.forename: R
authors.initials: R
authors.lastname: Beier
authors.forename: G
authors.initials: G
authors.lastname: Cario
authors.forename: A
authors.initials: A
authors.lastname: Schrauder
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000266:history*; D001215:Asparaginase / Q000266:history; D002648:Child; D003520:Cyclophosphamide / Q000266:history; D003561:Cytarabine / Q000266:history; D003630:Daunorubicin / Q000266:history; D005060:Europe; D005858:Germany; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008495:Medical Oncology / Q000266:history*; D015122:Mercaptopurine / Q000266:history; D008727:Methotrexate / Q000266:history; D010372:Pediatrics / Q000266:history*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000266:history*; D011241:Prednisone / Q000266:history; D016032:Randomized Controlled Trials as Topic / Q000266:history*; D014750:Vincristine / Q000266:history
chemical_list: D003561:Cytarabine; D014750:Vincristine; D003520:Cyclophosphamide; D015122:Mercaptopurine; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin