title: Detection of central nervous system involvement in childhood acute lymphoblastic leukemia by cytomorphology and flow cytometry of the cerebrospinal fluid.
abstract: BACKGROUND
  Therapy directed at the central nervous system (CNS) is an essential part of the treatment for childhood acute lymphoblastic leukemia (ALL). The current evaluation of CNS involvement based on cytomorphological examination of the cerebrospinal fluid (CSF) alone is not as sensitive with low cell counts as flow cytometric immunophenotyping (FCI) of the CSF. However, the importance of low CSF blasts counts at diagnosis is uncertain. We sought to determine the significance of FCI in relation to conventional morphological examination.
  
  
  METHODS
  We retrospectively compared FCI of the CSF with cytomorphology at diagnosis or relapse of childhood ALL. All patients were diagnosed 2000-2012 in Stockholm or Umeå, Sweden. Clinical data were collected from medical records and the Nordic leukemia registry. Treatment assignment was based on morphological examination only.
  
  
  RESULTS
  The cohort was comprised of 214 patients with ALL. CSF involvement was detected by both methods in 20 patients, in 17 by FCI alone, and in one patient by cytomorphology alone. The relapse rate was higher for patients with negative cytology but positive FCI compared to those without CNS involvement using both methods. The difference was especially marked in the current protocol. However, none of the patients with negative CSF cytology but positive FCI had a CNS relapse.
  
  
  CONCLUSIONS
  FCI of the CSF increased the detection rate of CNS involvement of ALL approximately two times compared to cytomorphology. Patients with low-level CNS involvement may benefit from additional intensified systemic or CNS-directed therapy, but larger studies are needed.
authors.affiliation: Childhood Cancer Research Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Ranta
authors.forename: Frans
authors.initials: F
authors.lastname: Nilsson
authors.forename: Arja
authors.initials: A
authors.lastname: Harila-Saari
authors.forename: Leonie
authors.initials: L
authors.lastname: Saft
authors.forename: Edneia
authors.initials: E
authors.lastname: Tani
authors.forename: Stefan
authors.initials: S
authors.lastname: Söderhäll
authors.forename: Anna
authors.initials: A
authors.lastname: Porwit
authors.forename: Magnus
authors.initials: M
authors.lastname: Hultdin
authors.forename: Ulrika
authors.initials: U
authors.lastname: Noren-Nyström
authors.forename: Mats
authors.initials: M
authors.lastname: Heyman
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D002555:Cerebrospinal Fluid / Q000166:cytology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid*; D012008:Recurrence
keywords: cerebrospinal fluid; cytology; flow cytometric immunophenotyping; leukemia