Outcomes and Risks of Granulocyte Colony-Stimulating Factor in Patients With Coronary Artery Disease

Harvard University, Cambridge, Massachusetts, United States
Journal of the American College of Cardiology (Impact Factor: 15.34). 12/2005; 46(9):1643-8. DOI: 10.1016/j.jacc.2005.01.067
Source: PubMed

ABSTRACT Cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia.
Patients with coronary artery disease (CAD) have low numbers of endothelial progenitor cells compared with healthy subjects.
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.
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.
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.

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Available from: Jonathan Michael Hill, Mar 09, 2014
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    • "G-CSF-mobilized hematopoietic cell grafts are currently the preferred source for hematopoietic cell transplantation (Gratwohl et al., 2005; To et al., 2011, and references within) and stem cell gene therapy applications (Ott et al., 2006; Cartier et al., 2009; Boztug et al., 2010; Sadelain et al., 2010). G- CSF mobilization, however, is associated with certain morbidities (Falzetti et al., 1999; Hill et al., 2005); furthermore, a number of patients fail to mobilize effectively or certain normal donors need to undergo extended aphereses (Anderlini et al., 1997; Stiff et al., 2000; Miller et al., 2008). In addition, certain limitations have been raised with the use of G-CSF in autologous transplantation settings, including gene therapy. "
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    • "The G-CSF treatment protocol used here has been evaluated to promote cardiac regeneration in patients with MI (Orlic et al., 2001; Kocker et al., 2001; Zohlnhö fer et al., 2006; Ince et al., 2005; Ripa et al., 2006; Ellis et al., 2006; Hill et al., 2005). These trials have been disappointing, with only 1 out of 5 trials showing any significant clinical benefit (Zohlnhö fer et al., 2006; Ince et al., 2005; Ripa et al., 2006; Ellis et al., 2006; Hill et al., 2005). As we reveal here, such limited clinical success might be because G-CSF administration is not a particularly efficacious regimen for mobilizing EPCs or SPCs, which may be important for cardiac regeneration. "
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