title: Phase I study of intravenous low-dose granulocyte colony-stimulating factor in acute and subacute ischemic stroke.
abstract: BACKGROUND
  Granulocyte colony-stimulating factor (G-CSF; filgrastim) may be useful for the treatment of acute ischemic stroke because of its neuroprotective and neurogenesis-promoting properties, but an excessive increase of neutrophils may lead to brain injury. We examined the safety and tolerability of low-dose G-CSF and investigated the effectiveness of G-CSF given intravenously in the acute phase (at 24 hours) or subacute phase (at 7 days) of ischemic stroke.
  
  
  METHODS
  Three intravenous dose regimens (150, 300, or 450 μg/body/day, divided into 2 doses for 5 days) of G-CSF were examined in 18 patients with magnetic resonance imaging (MRI)-confirmed infarct in the territory of the middle cerebral artery. Nine patients received the first dose at 24 hours poststroke (acute group) and 9 patients received the first dose on day 7 poststroke (subacute group; n = 3 at each dose in each group). A scheduled administration of G-CSF was skipped if the patient's leukocyte count exceeded 40,000/μL. Patients received neurologic and MRI examinations.
  
  
  RESULTS
  We found neither serious adverse event, drug-related platelet reduction nor splenomegaly. Leukocyte levels remained below 40,000/μL at 150 and 300 μg G-CSF/body/day, but rose above 40,000/μL at 450 μg G-CSF/body/day. Neurologic function improvement between baseline and day 90 was more marked after treatment in the acute phase versus the subacute phase (Barthel index 49.4 ± 28.1 v 15.0 ± 22.0; P < .01).
  
  
  CONCLUSIONS
  Low-dose G-CSF (150 and 300 μg/body/day) was safe and well tolerated in ischemic stroke patients, and leukocyte levels remained below 40,000/μL.
authors.affiliation: Division of Neurology, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Moriya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizuma
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Uesugi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ohnuki
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Nagata
authors.forename: Wakoh
authors.initials: W
authors.lastname: Takahashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawada
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Takagi
authors.forename: Shunya
authors.initials: S
authors.lastname: Takizawa
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor