title: Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95.
abstract: The trial ALL-BFM 95 for treatment of childhood acute lymphoblastic leukemia was designed to reduce acute and long-term toxicity in selected patient groups with favorable prognosis and to improve outcome in poor-risk groups by treatment intensification. These aims were pursued through a stratification strategy using white blood cell count, age, immunophenotype, treatment response, and unfavorable genetic aberrations providing an excellent discrimination of risk groups. Estimated 6-year event-free survival (6y-pEFS) for all 2169 patients was 79.6% (+/- 0.9%). The large standard-risk (SR) group (35% of patients) achieved an excellent 6y-EFS of 89.5% (+/- 1.1%) despite significant reduction of anthracyclines. In the medium-risk (MR) group (53% of patients), 6y-pEFS was 79.7% (+/- 1.2%); no improvement was accomplished by the randomized use of additional intermediate-dose cytarabine after consolidation. Omission of preventive cranial irradiation in non-T-ALL MR patients was possible without significant reduction of EFS, although the incidence of central nervous system relapses increased. In the high-risk (HR) group (12% of patients), intensification of consolidation/reinduction treatment led to considerable improvement over the previous ALL-BFM trials yielding a 6y-pEFS of 49.2% (+/- 3.2%). Compared without previous trial ALL-BFM 90, consistently favorable results in non-HR patients were achieved with significant treatment reduction in the majority of these patients.
authors.affiliation: Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Helmut
authors.initials: H
authors.lastname: Gadner
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.forename: Michael
authors.initials: M
authors.lastname: Dördelmann
authors.forename: Lutz
authors.initials: L
authors.lastname: Löning
authors.forename: Rita
authors.initials: R
authors.lastname: Beier
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.forename: Richard
authors.initials: R
authors.lastname: Ratei
authors.forename: Jochen
authors.initials: J
authors.lastname: Harbott
authors.forename: Joachim
authors.initials: J
authors.lastname: Boos
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.forename: Felix
authors.initials: F
authors.lastname: Niggli
authors.forename: Andreas
authors.initials: A
authors.lastname: Feldges
authors.forename: Günter
authors.initials: G
authors.lastname: Henze
authors.forename: Karl
authors.initials: K
authors.lastname: Welte
authors.forename: Jörn-Dirk
authors.initials: JD
authors.lastname: Beck
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Charlotte
authors.initials: C
authors.lastname: Niemeyer
authors.forename: Felix
authors.initials: F
authors.lastname: Zintl
authors.forename: Udo
authors.initials: U
authors.lastname: Bode
authors.forename: Christian
authors.initials: C
authors.lastname: Urban
authors.forename: Helmut
authors.initials: H
authors.lastname: Wehinger
authors.forename: Dietrich
authors.initials: D
authors.lastname: Niethammer
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Riehm
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation; D003561:Cytarabine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018570:Risk Assessment; D055502:Secondary Prevention; D016019:Survival Analysis
chemical_list: D003561:Cytarabine