title: Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children.
abstract: The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.
authors.affiliation: Service d'Hématologie et d'Oncologie Pédiatrique Hôpital d'Enfant Armand Trousseau, AP-HP, Paris, France.
authors.forename: M N
authors.initials: MN
authors.lastname: Dufourg
authors.forename: J
authors.initials: J
authors.lastname: Landman-Parker
authors.forename: M F
authors.initials: MF
authors.lastname: Auclerc
authors.forename: C
authors.initials: C
authors.lastname: Schmitt
authors.forename: Y
authors.initials: Y
authors.lastname: Perel
authors.forename: G
authors.initials: G
authors.lastname: Michel
authors.forename: P
authors.initials: P
authors.lastname: Levy
authors.forename: G
authors.initials: G
authors.lastname: Couillault
authors.forename: V
authors.initials: V
authors.lastname: Gandemer
authors.forename: M D
authors.initials: MD
authors.lastname: Tabone
authors.forename: F
authors.initials: F
authors.lastname: Demeocq
authors.forename: J P
authors.initials: JP
authors.lastname: Vannier
authors.forename: T
authors.initials: T
authors.lastname: Leblanc
authors.forename: G
authors.initials: G
authors.lastname: Leverger
authors.forename: A
authors.initials: A
authors.lastname: Baruchel
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001928:Brain Diseases, Metabolic / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D009498:Neurotoxins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy; D018570:Risk Assessment
chemical_list: D000964:Antimetabolites, Antineoplastic; D009498:Neurotoxins; D008727:Methotrexate