Granulocyte colony stimulating factor in patients with large acute myocardial infarction: results of a pilot dose-escalation randomized trial.
BACKGROUND
Preclinical studies suggest that administration of cytokines to mobilize stem cells and alter the postinfarction inflammatory cardiac milieu may enhance left ventricular function and survival.


METHODS
Eighteen patients were randomized in a 2:1 double-blind fashion to granulocyte colony stimulating factor (G-CSF) (at 5 escalating to 10 microg/kg per day subcutaneously for 5 days [6 patients in each group]) or matching placebo. Principal safety and efficacy end points were rupture-free survival and recovery of left ventricular function, respectively. Mobilization into the systemic circulation of precursor CD34+ and CD117+ stem cells at 30 days were also assessed.


RESULTS
Baseline characteristics of the 3 groups were well matched. Mean +/- SD creatine kinase-MB maximum was 349 (169) IU. Follow-up averaged 30 +/- 6, 21 +/- 11, and 11 +/- 6 months in the 3 groups, respectively. Precursor cell mobilization increased by a factor of 5 to 7 in the G-CSF-treated patients. There were no deaths or myocardial ruptures leading to tamponade through 30 days. Baseline and 30-day left ventricular ejection fraction in the placebo, 5-microg, and 10-microg dose groups were 33.7% (1.6) and 41.7% (8.2), 36.8% (7.5) and 41.3% (10.3), and 33.5% (4.8) and 38.7% (7.3), respectively (P = NS for all between-group comparisons). No differences between the G-CSF and placebo groups were noted in any other measure of left ventricular systolic or diastolic function 30 days after infarction.


CONCLUSIONS
Despite demonstrated mobilization of precursor stem cells in a timely fashion, in this small, pilot-scale randomized trial involving patients with large myocardial infarction, we were unable to demonstrate improvement in left ventricular function at 30 days.
Ellis
Stephen G
SG
Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Penn
Marc S
MS
Bolwell
Brian
B
Garcia
Mario
M
Chacko
Matthews
M
Wang
Thomas
T
Brezina
Kelly J
KJ
McConnell
Gerry
G
Topol
Eric J
EJ
D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010865:Pilot Projects; D013318:Stroke Volume; D016277:Ventricular Function, Left
D016179:Granulocyte Colony-Stimulating Factor