title: Safety and efficacy of consecutive cycles of granulocyte-colony stimulating factor, and an intracoronary CD133+ cell infusion in patients with chronic refractory ischemic heart disease: the G-CSF in angina patients with IHD to stimulate neovascularization (GAIN I) trial.
abstract: BACKGROUND
  Preclinical studies suggest granulocyte-colony stimulating factor (G-CSF) holds promise for treating ischemic heart disease; however; its clinical safety and efficacy in this setting remain unclear. We elected to evaluate the safety and efficacy of G-CSF administration in patients with refractory "no-option" ischemic heart disease.
  
  
  METHODS
  Twenty patients (18 males, 2 females, mean age 62.4 years) were enrolled and underwent baseline cardiac ischemia assessment (CA) (angina questionnaire, exercise stress test [EST], technetium Tc 99m sestamibi and dobutamine-stress echocardiographic imaging). Patients then received open-label G-CSF commencing at 10 microg/kg SC for 5 days, with an EST on days 4 and 6 (to facilitate myocardial cytokine generation and stem cell trafficking). After 3 months, CA and the same regimen of G-CSF+ESTs were repeated but, in addition, leukapheresis and a randomized double-blinded intracoronary infusion of CD133+ or unselected cells were performed. Final CA occurred 3 months thereafter.
  
  
  RESULTS
  There were no deaths, but only 16 patients were permitted to complete the study. Eight events fulfilled prespecified "adverse event" criteria, including 4 troponin I-positive events and 2 episodes of thrombocytopenia. Also, frequent minor troponin I-positive events (troponin I<0.9 microg/L) were observed, which did not meet adverse event criteria. The administration of consecutive cycles of G-CSF resulted in stepwise improvements in anginal frequency, EST performance, and Duke treadmill scores (all P<.005). However, from baseline to final follow-up, technetium Tc 99m sestamibi and dobutamine-stress echocardiographic results were unchanged.
  
  
  CONCLUSIONS
  Granulocyte-colony stimulating factor administration was associated with improvement in a range of subjective outcomes. However, adverse events were common, and objective measures of cardiac perfusion/ischemia were unchanged.
authors.affiliation: Victor Chang Cardiac Research Institute, St Vincent's Hospital, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Kovacic
authors.forename: Peter
authors.initials: P
authors.lastname: Macdonald
authors.forename: Michael P
authors.initials: MP
authors.lastname: Feneley
authors.forename: David W M
authors.initials: DW
authors.lastname: Muller
authors.forename: Judith
authors.initials: J
authors.lastname: Freund
authors.forename: Anthony
authors.initials: A
authors.lastname: Dodds
authors.forename: Sam
authors.initials: S
authors.lastname: Milliken
authors.forename: Helen
authors.initials: H
authors.lastname: Tao
authors.forename: Silviu
authors.initials: S
authors.lastname: Itescu
authors.forename: John
authors.initials: J
authors.lastname: Moore
authors.forename: David
authors.initials: D
authors.lastname: Ma
authors.forename: Robert M
authors.initials: RM
authors.lastname: Graham
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000628:therapy*; D033581:Stem Cell Transplantation
chemical_list: D016179:Granulocyte Colony-Stimulating Factor