Granulocyte colony stimulating factor in patients with large acute myocardial infarction

Results of a pilot dose-escalation randomized trial

Stephen G. Ellis, Marc S. Penn, Brian Bolwell, Mario J. Garcia, Matthews Chacko, Thomas Wang, Kelly J. Brezina, Gerry McConnell, Eric J. Topol

Research output: Contribution to journalArticle

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Abstract

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 μg/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-μg, and 10-μg 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.

Original languageEnglish (US)
JournalAmerican Heart Journal
Volume152
Issue number6
DOIs
StatePublished - Dec 2006
Externally publishedYes

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Granulocyte Colony-Stimulating Factor
Myocardial Infarction
Left Ventricular Function
Placebos
Rupture
Stem Cells
Hematopoietic Stem Cell Mobilization
MB Form Creatine Kinase
Survival
Stroke Volume
Infarction
Cytokines
Safety

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Granulocyte colony stimulating factor in patients with large acute myocardial infarction : Results of a pilot dose-escalation randomized trial. / Ellis, Stephen G.; Penn, Marc S.; Bolwell, Brian; Garcia, Mario J.; Chacko, Matthews; Wang, Thomas; Brezina, Kelly J.; McConnell, Gerry; Topol, Eric J.

In: American Heart Journal, Vol. 152, No. 6, 12.2006.

Research output: Contribution to journalArticle

Ellis, Stephen G. ; Penn, Marc S. ; Bolwell, Brian ; Garcia, Mario J. ; Chacko, Matthews ; Wang, Thomas ; Brezina, Kelly J. ; McConnell, Gerry ; Topol, Eric J. / Granulocyte colony stimulating factor in patients with large acute myocardial infarction : Results of a pilot dose-escalation randomized trial. In: American Heart Journal. 2006 ; Vol. 152, No. 6.
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abstract = "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 μg/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-μg, and 10-μg 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.",
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AU - Garcia, Mario J.

AU - Chacko, Matthews

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AU - McConnell, Gerry

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