Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease.
OBJECTIVE
Cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia.


BACKGROUND
Patients with coronary artery disease (CAD) have low numbers of endothelial progenitor cells compared with healthy subjects.


METHODS
Granulocyte colony-stimulating factor (G-CSF), 10 microg/kg/day for five days, was administered to 16 CAD patients. Progenitor cells were measured by flow cytometry; ischemia was assessed by exercise stress testing and by dobutamine stress cardiac magnetic resonance imaging.


RESULTS
Granulocyte colony-stimulating factor increased CD34+/CD133+ cells in the circulation from 1.5 +/- 0.2 microl to 52.4 +/- 10.4 microl (p < 0.001), similar to the response observed in 15 healthy subjects (75.1 +/- 12.6 microl, p = 0.173). Indices of platelet and coagulation activation were not changed by treatment, but C-reactive protein increased from 4.5 +/- 1.3 mg/l to 8.6 +/- 1.3 mg/l (p = 0.017). Two patients experienced serious adverse events: 1) non-ST-segment elevation myocardial infarction (MI) 8 h after the fifth G-CSF dose, and 2) MI and death 17 days after treatment. At 1 month after treatment, there was no improvement from baseline values (i.e., reduction) in wall motion score (from 25.7 +/- 2.1 to 28.3 +/- 1.9, p = 0.196) or segments with abnormal perfusion (7.6 +/- 1.1 to 7.7 +/- 1.1, p = 0.916) and a trend towards a greater number of ischemic segments (from 4.5 +/- 0.6 to 6.1 +/- 1.0, p = 0.068). There was no improvement in exercise duration at 1 month (p = 0.37) or at 3 months (p = 0.98) versus baseline.


CONCLUSIONS
Granulocyte colony-stimulating factor administration to CAD patients mobilizes cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients.
Hill
Jonathan M
JM
Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA. Jonathan.Hill@kcl.ac.uk
Syed
Mushabbar A
MA
Arai
Andrew E
AE
Powell
Tiffany M
TM
Paul
Jonathan D
JD
Zalos
Gloria
G
Read
Elizabeth J
EJ
Khuu
Hanh M
HM
Leitman
Susan F
SF
Horne
McDonald
M
Csako
Gyorgy
G
Dunbar
Cynthia E
CE
Waclawiw
Myron A
MA
Cannon
Richard O
RO
D000368:Aged; D003324:Coronary Artery Disease / Q000188:drug therapy*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome
D016178:Granulocyte-Macrophage Colony-Stimulating Factor