title: Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951.
abstract: The European Organisation for Research and Treatment of Cancer 58951 trial for children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) addressed 3 randomized questions, including the evaluation of dexamethasone (DEX) versus prednisolone (PRED) in induction and, for average-risk patients, the evaluation of vincristine and corticosteroid pulses during continuation therapy. The corticosteroid used in the pulses was that assigned at induction. Overall, 411 patients were randomly assigned: 202 initially randomly assigned to PRED (60 mg/m(2)/d), 201 to DEX (6 mg/m(2)/d), and 8 nonrandomly assigned to PRED. At a median follow-up of 6.3 years, there were 19 versus 34 events for pulses versus no pulses; 6-year disease-free survival (DFS) rate was 90.6% (standard error [SE], 2.1%) and 82.8% (SE, 2.8%), respectively (hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in the PRED (HR = 0.56) and DEX groups (HR = 0.59) but more pronounced in girls (HR = 0.24) than in boys (HR = 0.71). Grade 3 to 4 hepatic toxicity was 30% versus 40% in pulses versus no pulses group and grade 2 to 3 osteonecrosis was 4.4% versus 2%. For average-risk patients treated according to Berlin-Frankfurt-Muenster-based protocols, pulses should become a standard component of therapy.
authors.affiliation: Department of Pediatric Hematology-Oncology, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium. barbara.demoerloose@ugent.be
authors.forename: Barbara
authors.initials: B
authors.lastname: De Moerloose
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.forename: Françoise
authors.initials: F
authors.lastname: Mazingue
authors.forename: Alain
authors.initials: A
authors.lastname: Robert
authors.forename: Anne
authors.initials: A
authors.lastname: Uyttebroeck
authors.forename: Karima
authors.initials: K
authors.lastname: Yakouben
authors.forename: Alice
authors.initials: A
authors.lastname: Ferster
authors.forename: Geneviève
authors.initials: G
authors.lastname: Margueritte
authors.forename: Patrick
authors.initials: P
authors.lastname: Lutz
authors.forename: Martine
authors.initials: M
authors.lastname: Munzer
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sirvent
authors.forename: Lucilia
authors.initials: L
authors.lastname: Norton
authors.forename: Patrick
authors.initials: P
authors.lastname: Boutard
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.forename: Frederic
authors.initials: F
authors.lastname: Millot
authors.forename: Pierre
authors.initials: P
authors.lastname: Philippet
authors.forename: Liliana
authors.initials: L
authors.lastname: Baila
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoit
authors.forename: Jacques
authors.initials: J
authors.lastname: Otten
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D010020:Osteonecrosis / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D011239:Prednisolone / Q000008:administration & dosage; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000305:Adrenal Cortex Hormones; D014750:Vincristine; D003907:Dexamethasone; D011239:Prednisolone
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