title: Granulocyte-colony stimulating factor for mobilizing bone marrow stem cells in subacute stroke: the stem cell trial of recovery enhancement after stroke 2 randomized controlled trial.
abstract: OBJECTIVE
  Granulocyte-colony stimulating factor (G-CSF) is neuroprotective in experimental stroke and mobilizes CD34(+) peripheral blood stem cells into the circulation. We assessed the safety of G-CSF in recent stroke in a phase IIb single-center randomized, controlled trial.
  
  
  METHODS
  G-CSF (10 μg/kg) or placebo (ratio 2:1) was given SC for 5 days to 60 patients 3 to 30 days after ischemic or hemorrhagic stroke. The primary outcome was the frequency of serious adverse events. Peripheral blood counts, CD34(+) count, and functional outcome were measured. MRI assessed lesion volume, atrophy, and the presence of iron-labeled CD34(+) cells reinjected on day 6.
  
  
  RESULTS
  Sixty patients were recruited at mean of 8 days (SD ± 5) post ictus, with mean age 71 years (± 12 years) and 53% men. The groups were well matched for baseline minimization/prognostic factors. There were no significant differences between groups in the number of participants with serious adverse events: G-CSF 15 (37.5%) of 40 versus placebo 7 (35%) of 20, death or dependency (modified Rankin Score: G-CSF 3.3 ± 1.3, placebo 3.0 ± 1.3) at 90 days, or the number of injections received. G-CSF increased CD34(+) and total white cell counts of 9.5- and 4.2-fold, respectively. There was a trend toward reduction in MRI ischemic lesion volume with respect to change from baseline in G-CSF-treated patients (P=0.06). In 1 participant, there was suggestion that labeled CD34(+) cells had migrated to the ischemic lesion.
  
  
  CONCLUSIONS
  This randomized, double-blind, placebo-controlled trial suggests that G-CSF is safe when administered subacutely. It is feasible to label and readminister iron-labeled CD34(+) cells in patients with ischemic stroke.
  
  
  BACKGROUND
  URL: www.controlled-trials.com. Unique identifier: ISRCTN63336619.
authors.affiliation: Stroke Trials Unit, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: England
authors.forename: Maryam
authors.initials: M
authors.lastname: Abaei
authors.forename: Dorothee P
authors.initials: DP
authors.lastname: Auer
authors.forename: James
authors.initials: J
authors.lastname: Lowe
authors.forename: D Rhodri E
authors.initials: DR
authors.lastname: Jones
authors.forename: Gillian
authors.initials: G
authors.lastname: Sare
authors.forename: Marion
authors.initials: M
authors.lastname: Walker
authors.forename: Philip M W
authors.initials: PM
authors.lastname: Bath
mesh_terms: D000368:Aged; D018952:Antigens, CD34; D001854:Bone Marrow Cells / Q000187:drug effects*; D001921:Brain / Q000166:cytology; D002545:Brain Ischemia / Q000150:complications; D002543:Cerebral Hemorrhage / Q000150:complications; D004311:Double-Blind Method; D017352:Echo-Planar Imaging; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D020127:Recovery of Function; D020521:Stroke / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D005343:Fibrinolytic Agents; D016188:Receptors, Granulocyte Colony-Stimulating Factor