title: Disseminated lymphoblastic lymphoma in children and adolescents: results of the COG A5971 trial: a report from the Children's Oncology Group.
abstract: The Children's Oncology Group's A5971 trial examined central nervous system (CNS) prophylaxis and early intensification in paediatric patients diagnosed with CNS-negative Stage III and IV lymphoblastic lymphoma. Using a 2 × 2 factorial design, the study randomized patients to Children's Cancer Group (CCG) modified Berlin-Frankfurt-Muenster (BFM) acute lymphoblastic leukaemia (ALL) regimen with intensified intrathecal (IT) methotrexate (MTX) (Arm A1) or an adapted non-Hodgkin lymphoma/BFM-95 therapy with high dose MTX in interim maintenance but no IT-MTX in maintenance (Arm B1). Each cohort was randomized ± intensification (cyclophosphamide/anthracycline) (Arms A2/B2). For the 254 randomized patients, there was no difference in 5-year event-free survival (EFS) for the four arms: Arm A1, 80% [95% confidence interval (CI) 67-89%] and Arm A2, 81% (95% CI 69-89%); Arm B1, 80% (95% CI 68-88%) and Arm B2, 84% (95% CI 72-91%). The cumulative incidence of CNS relapse was 1·2%. Age <10 years and institutional imaging response at 2 weeks was associated with improved outcomes (P < 0·001 and P = 0·014 for overall survival). CNS positive patients (n = 12) did poorly [5-year EFS of 63% (95% CI 29-85%)]. For CNS-negative patients, there was no difference in outcome based on CNS prophylaxis (IT-MTX versus HD-MTX) or with intensification.
authors.affiliation: Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Termuhlen
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Smith
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
authors.forename: Mark
authors.initials: M
authors.lastname: Lones
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Finlay
authors.forename: Howard
authors.initials: H
authors.lastname: Weinstein
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gross
authors.forename: Minnie
authors.initials: M
authors.lastname: Abromowitch
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000517:prevention & control / Q000556:secondary; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018943:Anthracyclines; D003520:Cyclophosphamide; D008727:Methotrexate
keywords: lymphoblastic lymphoma; non-Hodgkin lymphoma; paediatric