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.
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.
Kovacic
Jason C
JC
Victor Chang Cardiac Research Institute, St Vincent's Hospital, University of New South Wales, Sydney, New South Wales, Australia.
Macdonald
Peter
P
Feneley
Michael P
MP
Muller
David W M
DW
Freund
Judith
J
Dodds
Anthony
A
Milliken
Sam
S
Tao
Helen
H
Itescu
Silviu
S
Moore
John
J
Ma
David
D
Graham
Robert M
RM
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
D016179:Granulocyte Colony-Stimulating Factor