title: Prognostic significance of the initial cerebro-spinal fluid (CSF) involvement of children with acute lymphoblastic leukaemia (ALL) treated without cranial irradiation: results of European Organization for Research and Treatment of Cancer (EORTC) Children Leukemia Group study 58881.
abstract: OBJECTIVE
  To evaluate the prognostic significance of the initial cerebro-spinal fluid (CSF) involvement of children with ALL enrolled from 1989 to 1996 in the EORTC 58881 trial.
  
  
  METHODS
  Patients (2025) were categorised according to initial central nervous system (CNS) status: CNS-1 (CNS negative, n=1866), CNS-2 (<5 leucocytes/mm(3), CSF with blasts, n=50), CNS-3 (CNS positive, n=49), TLP+ (TLP with blasts, n=60). CNS-directed therapy consisted in intravenous (i.v.) methotrexate (5 g/sqm) in 4-10 courses, and intrathecal methotrexate injections (10-20), according to CNS status. Cranial irradiation was omitted in all patients.
  
  
  RESULTS
  In the CNS1, TLP+, CNS2 and CNS3 group the 8-year EFS rate (SE%) was 69.7% (1.1%), 68.8% (6.2%), 71.3% (6.5%) and 68.3% (6.2%), respectively. The 8-year incidence of isolated CNS relapse (SE%) was 3.4% (0.4%), 1.7% (1.7%), 6.1% (3.5%) and 9.4% (4.5%), respectively, whereas the 8-year isolated or combined CNS relapse incidence was 7.6% (0.6%), 3.5% (2.4%), 10.2% (4.4%) and 11.7% (5.0%), respectively. Patients with CSF blasts had a higher rate of initial bad risk features. Multivariate analysis indicated that presence of blasts in the CSF had no prognostic value: (i) for EFS and OS; (ii) for isolated and isolated or combined CNS relapse; WBC count<25 × 10(9)/L and Medac E-coli asparaginase treatment were each related to a lower CNS relapse risk.
  
  
  CONCLUSIONS
  The presence of initial CNS involvement has no prognostic significance in EORTC 58881. Intensification of CNS-directed chemotherapy, without CNS radiation, is an effective treatment of initial meningeal leukaemic involvement.
authors.affiliation: Department of Pediatrics, CHU Nice, France. sirvent.n@chu-nice.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sirvent
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Xavier
authors.initials: X
authors.lastname: Rialland
authors.forename: Frédéric
authors.initials: F
authors.lastname: Millot
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoit
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.forename: Alice
authors.initials: A
authors.lastname: Ferster
authors.forename: Alain
authors.initials: A
authors.lastname: Robert
authors.forename: Patrick
authors.initials: P
authors.lastname: Lutz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Nelken
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Plouvier
authors.forename: Lucilia
authors.initials: L
authors.lastname: Norton
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.forename: Jacques
authors.initials: J
authors.lastname: Otten
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000401:mortality; D002555:Cerebrospinal Fluid / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D007962:Leukocytes; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000401:mortality; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000379:methods