title: Methotrexate infusions as central nervous system prophylaxis in children with acute lymphocytic leukemia: the Norwegian experience.
abstract: This study included all 690 children in Norway diagnosed as having acute lymphocytic leukemia (ALL) from July 1975 till the end of 1997. Relapses and deaths were monitored until the end of 2000. Neuroleukemia prophylaxis was intravenous methotrexate (MTX) infusions as intermediate-dose methotrexate (IDM) or high-dose methotrexate (HDM) combined with intrathecal MTX. From 1992, systemic therapy was considerably intensified, and, in addition, patients in a subgroup of the high-risk and very high-risk groups were given prophylactic cranial irradiation. The overall findings showed that MTX significantly reduced central nervous system (CNS)-related relapses, and, in general, reinforced systemic therapy reduced significantly non-CNS relapses and deaths. The overall crude survival was 75%. During the study period, the crude survival improved for patients on standard protocols from initially 65 to 90%. Forty patients (6%) developed isolated CNS relapse, 27 (4%) had combined CNS relapse, whereas 180 (26%) had non-CNS relapse. When IDM and HDM were compared, the cumulative risk for isolated CNS relapse was significantly lower with HDM, 12 and 5%, respectively. For any relapses that involved the CNS, the risk remained significantly lower for HDM, 8 versus 18%. Of the 40 patients with isolated CNS relapse, 23 survived (58%).
authors.affiliation: Department of Pediatrics, St. Olav's Hospital, Trondheim, Norway.
authors.forename: Peter Johan
authors.initials: PJ
authors.lastname: Moe
authors.forename: Are
authors.initials: A
authors.lastname: Holen
authors.forename: Randi
authors.initials: R
authors.lastname: Nygaard
authors.forename: Anders
authors.initials: A
authors.lastname: Glomstein
authors.forename: Birgit
authors.initials: B
authors.lastname: Madsen
authors.forename: Marit
authors.initials: M
authors.lastname: Hellebostad
authors.forename: Tore
authors.initials: T
authors.lastname: Stokland
authors.forename: Karl Wilhelm
authors.initials: KW
authors.lastname: Wefring
authors.forename: Jon
authors.initials: J
authors.lastname: Steen-Johnsen
authors.forename: Bjørn
authors.initials: B
authors.lastname: Nielsen
authors.forename: Clare
authors.initials: C
authors.lastname: Hapnes
authors.forename: Sigurd
authors.initials: S
authors.lastname: Børsting
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000517:prevention & control* / Q000556:secondary; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004334:Drug Administration Schedule; D006801:Humans; D007223:Infant; D007260:Infusion Pumps; D007278:Injections, Spinal; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local; D009664:Norway / Q000453:epidemiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000453:epidemiology / Q000532:radiotherapy; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate