title: Leukemic blasts are present at low levels in spinal fluid in one-third of childhood acute lymphoblastic leukemia cases.
abstract: Central nervous system (CNS) involvement is associated with relapse in childhood acute lymphoblastic leukemia (ALL) and is a diagnostic challenge.
  
  
  
  In a Nordic/Baltic prospective study, we assessed centralized flow cytometry (FCM) of locally fixed cerebrospinal fluid (CSF) samples versus local conventional cytospin-based cytology (CC) for detecting leukemic cells and evaluating kinetics of elimination of leukemic cells in CSF.
  
  
  
  Among 300 patients with newly diagnosed ALL, 87 (29%) had CSF involvement by FCM, while CC was positive in 30 (10%) of 299 patients with available CC data (P < 0.001). Patients with FCM+/CC+ had higher CSF leukemic blast counts compared to patients positive by FCM only (medians: 0.10 vs. 0.017 leukemic blasts/μl, P = 0.006). Patients positive by FCM had higher white blood cell counts in peripheral blood than patients negative by FCM (medians: 45 × 10(9) /l vs. 10 × 10(9) /l, P < 0.001), were younger (medians: 3 years vs. 4 years, P = 0.03), and more frequently had T-cell ALL (18/87 vs. 16/213, P = 0.001). At treatment day 15, five of 52 patients (10%) who had CSF positive by FCM at diagnosis remained so despite at least two doses of weekly intrathecal chemotherapy.
  
  
  
  Longer follow-up is needed to clarify whether FCM positivity has prognostic significance and is an indicator for intensified CNS-directed therapy.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Levinsen
authors.affiliation: Department of Clinical Immunology, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hanne V
authors.initials: HV
authors.lastname: Marquart
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Line
authors.initials: L
authors.lastname: Groth-Pedersen
authors.affiliation: Department of Pediatrics, Institution of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Abrahamsson
authors.affiliation: Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Birgitte K
authors.initials: BK
authors.lastname: Albertsen
authors.affiliation: Department of Clinical Genetics, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mette K
authors.initials: MK
authors.lastname: Andersen
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Frandsen
authors.affiliation: Department of Pediatrics, Astrid Lindgrens Hospital, Stockholm, Sweden.
authors.forename: Arja
authors.initials: A
authors.lastname: Harila-Saari
authors.affiliation: Department of Pediatrics, Skåne University Hospital, Lund, Sweden.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Pronk
authors.affiliation: Department of Pediatrics, Oslo University Hospital, Norway.
authors.forename: Aina
authors.initials: A
authors.lastname: Ulvmoen
authors.affiliation: Centre for Pediatric Oncology and Hematology, University Children's Hospital, Vilnius, Lithuania.
authors.forename: Goda
authors.initials: G
authors.lastname: Vaitkevičienė
authors.affiliation: Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: Päivi M
authors.initials: PM
authors.lastname: Lähteenmäki
authors.affiliation: Department of Pediatrics, Oulu University Hospital, Oulu, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Niinimäki
authors.affiliation: Children and Adolescents, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Mervi
authors.initials: M
authors.lastname: Taskinen
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Jeppesen
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark. kschmiegelow@rh.dk.|Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. kschmiegelow@rh.dk.|Division of Pediatric Hematology/Oncology, Perlmutter Cancer Center, NYU Langone Medical Center, New York. kschmiegelow@rh.dk.
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
mesh_terms: D000293:Adolescent; D001752:Blast Crisis / Q000134:cerebrospinal fluid*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007958:Leukocyte Count; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid / Q000473:pathology*
keywords: ALL; CSF leukemia; acute; leukemias; minimal residual disease