title: Advanced-stage large-cell lymphoma in children and adolescents: results of a randomized trial incorporating intermediate-dose methotrexate and high-dose cytarabine in the maintenance phase of the APO regimen: a Pediatric Oncology Group phase III trial.
abstract: OBJECTIVE
  The Pediatric Oncology Group adopted a histology-based approach to non-Hodgkin's lymphoma and treated patients with advanced large-cell lymphoma on a separate protocol (doxorubicin, vincristine, prednisone, 6-mercaptopurin, and methotrexate; APO regimen). In this study, we assessed the effects of an intense antimetabolite therapy alternating with APO on overall survival (OS) and event-free survival (EFS) and looked into biologic correlates.
  
  
  METHODS
  From December 1994 to April 2000, we enrolled 180 eligible pediatric patients with stage III/IV large-cell lymphoma (LCL); 90 patients were randomly assigned to the intermediate-dose methotrexate (IDM) and high-dose cytarabine (HiDAC) arm, 85 patients to the APO arm, and five patients directly to the APO arm by study design due to CNS involvement. Planned therapy duration was 12 months.
  
  
  RESULTS
  The 4-year EFS for all patients was 67.4% (SE, 4.2%), and OS was 80.1% (SE, 3.6%) without any significant difference between the two arms. The 4-year EFS and OS were 71.8% (SE, 6.1%) and 88.1% (SE, 4.4%), respectively, for patients with anaplastic large-cell lymphoma, and 63.8% (SE, 10.3%) and 70.3% (SE, 9.0%), respectively, for patients with diffuse large B-cell lymphoma. Only 11 patients required radiation (due to unresponsive bulky disease or CNS involvement). The IDM/HiDAC arm was associated with more toxicity.
  
  
  CONCLUSIONS
  The efficacy of incorporating IDM/HiDAC in the treatment plan of pediatric and adolescent patients with advanced-stage LCL was inconclusive as to its effect on EFS, regardless of the lymphoma phenotype. It cannot be excluded that with a higher number of patients, one treatment could prove superior and future studies will build on these data.
authors.affiliation: Department of Pediatrics, Medical College of Virginia, PO Box 980646, Richmond, VA 23298-0646, USA. jhlaver@hsc.vcu.edu
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Laver
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Kraveka
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hutchison
authors.forename: Myron
authors.initials: M
authors.lastname: Chang
authors.forename: James
authors.initials: J
authors.lastname: Kepner
authors.forename: Molly
authors.initials: M
authors.lastname: Schwenn
authors.forename: Nancy
authors.initials: N
authors.lastname: Tarbell
authors.forename: Sunil
authors.initials: S
authors.lastname: Desai
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Weinstein
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007278:Injections, Spinal; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D014750:Vincristine; D004317:Doxorubicin; D015122:Mercaptopurine; D011241:Prednisone; D008727:Methotrexate