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

• Published in: The American heart journal Vol. 156; no. 5; pp. 954 - 963
• Main Authors: Kovacic, Jason C., FRACP, PhD, Macdonald, Peter, FRACP, MD, PhD, Feneley, Michael P., FRACP, MD, Muller, David W.M., FRACP, MD, Freund, Judith, FRACP, Dodds, Anthony, FRACP, Milliken, Sam, FRACP, Tao, Helen, MD, PhD, Itescu, Silviu, FRACP, Moore, John, FRACP, MD, Ma, David, FRACP, MD, Graham, Robert M., FRACP, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.11.2008; Elsevier; Elsevier Limited
• Subjects: Adult; Aged; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Chemokines; Chronic Disease; Coronary heart disease; Defects; Diabetic retinopathy; Double-Blind Method; Feasibility studies; Female; Granulocyte Colony-Stimulating Factor - therapeutic use; Heart; Heart attacks; Hospitals; Humans; Infusions, Intra-Arterial; Ischemia; Male; Medical sciences; Middle Aged; Myocardial Ischemia - therapy; Myocarditis. Cardiomyopathies; Quality of life; Questionnaires; Stem Cell Transplantation; Human; Chronic disease; Toxicity; Coronary artery; Myocardial ischemia; Cardiovascular disease; Angina pectoris; Coronary heart disease; Myocardial disease; Cycle; Vascular disease; Refractory; Infusion; Granulocyte colony stimulating factor; Efficiency; Perfusion; Complication; Circulatory system; Neovascularization; Safety; Cardiology; Cell; Gain
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2008.04.034

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 μg/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 μg/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.