title: The effect of central nervous system involvement and irradiation in childhood acute lymphoblastic leukemia: Lessons from the NOPHO ALL-92 and ALL-2000 protocols.
abstract: Central nervous system irradiation (CNS-RT) has played a central role in the cure of acute lymphoblastic leukemia (ALL), but due to the risk of long-term toxicity, it is now considered a less-favorable method of CNS-directed therapy.
  
  
  
  Retrospectively, we estimated the effect of CNS involvement and CNS-RT on events and overall survival (OS) in 835 children treated for high-risk ALL in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000 trials.
  
  
  
  We did not observe a statistically significant difference in the OS or event-free survival (EFS) in patients with CNS involvement at diagnosis, but the risk of isolated CNS relapse was higher (hazard ratio [HR] 7.09, P < 0.001). CNS-RT was given to 169 of the 783 patients in first complete remission, of which 16 had CNS involvement at diagnosis. In general, CNS-RT improved EFS (HR 0.58, P < 0.05) but not OS (HR 0.69, P = n.s.). The adjusted HRs for all relapses, isolated bone marrow relapse, CNS-involving relapse, and isolated CNS relapse, were 0.47 (P < 0.01), 0.50 (P < 0.05), 0.34 (P < 0.01), and 0.12 (P < 0.01), respectively, in irradiated patients.
  
  
  
  CNS-RT was associated with an advantage in EFS by decreasing the risk of relapse but without improving OS.
authors.affiliation: Division of Pediatric Hematology-Oncology and Stem Cell Transplantation, Children and Adolescents, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Mervi
authors.initials: M
authors.lastname: Taskinen
authors.affiliation: Department of Pediatric Oncology, Astrid Lindgren Children's Hospital, Stockholm, Sweden.|Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
authors.forename: Trausti
authors.initials: T
authors.lastname: Oskarsson
authors.affiliation: Institute of Gynegology, Obstetrics, and Pediatrics, University of Copenhagen, Copenhagen, Denmark.|Department of Pediatrics, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Levinsen
authors.affiliation: Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.affiliation: Department of Pediatrics, Drammen Hospital, Oslo, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Hellebostad
authors.affiliation: Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Olafur Gisli
authors.initials: OG
authors.lastname: Jonsson
authors.affiliation: Children's Hospital, Turku University Hospital, Turku, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Lähteenmäki
authors.affiliation: Institute of Gynegology, Obstetrics, and Pediatrics, University of Copenhagen, Copenhagen, Denmark.|Department of Pediatrics, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
authors.affiliation: Department of Pediatric Oncology, Astrid Lindgren Children's Hospital, Stockholm, Sweden.|Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Heyman
mesh_terms: D000293:Adolescent; D016543:Central Nervous System Neoplasms / Q000209:etiology / Q000401:mortality / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000209:etiology / Q000401:mortality / Q000532:radiotherapy*; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000628:therapy; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
keywords: acute lymphoblastic leukemia; central nervous system; children; irradiation; risk factor