title: Intensive chemotherapy for systemic anaplastic large cell lymphoma in children and adolescents: final results of Children's Cancer Group Study 5941.
abstract: BACKGROUND
  Anaplastic large cell lymphoma (ALCL) is characterized by advanced disease at presentation (70-80% of pediatric cases) and accounts for 10-15% of all childhood lymphomas. Treatment strategies for pediatric ALCL vary from short pulse B-NHL chemotherapy to prolonged leukemia like therapy. The optimal treatment strategy is unknown.
  
  
  METHODS
  CCG-5941 used a compressed aggressive multiagent T-cell lineage chemotherapy regimen consisting of a 3-week induction therapy (vincristine, prednisone, cyclophosphamide, daunomycin, asparaginase) followed by a 3-week consolidation period (vincristine, prednisone, etoposide, 6-thioguanine, cytarabine, asparaginase, methotrexate) followed by six courses of maintenance chemotherapy at 7-week intervals (cyclophosphamide, 6-thioguanine, vincristine, prednisone, doxorubicin, asparaginase, methotrexate etoposide, cytarabine). Total therapy was 48 weeks.
  
  
  RESULTS
  Eighty-six children (male 56%, female 44%) with non-localized ALCL (CD30+) were treated. The majority of tumors were positive for ALK (90%) and of T lineage (83%). Extranodal disease was common (mediastinum 35%, skin 15%, lung 14%, bone 12%, bone marrow 13%, liver 6%, and other viscera 17%). Grade 4 neutropenia occurred in 82% of patients. The 5-year EFS was 68% (95% CI of 57-78%) and the 5-year OS was 80% (95% CI of 69-87%). There were 21 relapses and 4 toxic deaths as first events. Relapse occurred early with 17 (81%) relapses occurring within 2 years of diagnosis and 12 (57%) while receiving therapy. Univariate analysis for risk factors only identified bone marrow involvement predicting lower EFS (P = 0.03).
  
  
  CONCLUSIONS
  CCG-5941 demonstrated efficacy similar to previously reported regimens but with significant hematologic toxicity.
authors.affiliation: Division of Pediatric Hematology-Oncology, Children's Hospital of the King's Daughters, Norfolk, Virginia 23507, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lowe
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gross
authors.forename: Jonathan
authors.initials: J
authors.lastname: Finlay
authors.forename: David
authors.initials: D
authors.lastname: Zwick
authors.forename: Minnie
authors.initials: M
authors.lastname: Abromowitch
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015996:Survival Rate; D016896:Treatment Outcome