Bone Marrow-Derived Cell Mobilization with G-CSF and GM-CSF in Patients with Acute Myocardial Infarction: A Pilot Study on Feasibility, Safety and Efficacy.

Introduction. Intracoronary or intramyocardiac injection of bone marrow stem cells or growth factor-mobilized peripheral blood stem cells (PBSC) may contribute to myocardial regeneration and neovascularization of the ischemic myocardium either in animal models or in human. This effect is probably due to a selective colonization of the ischemic area by PBSC. Very few studies were done in the acute setting of ischemic heart disease, with controversial results. Aims of this pilot study were: i) to verify feasibility and safety of PBSC mobilization in patients with acute myocardial infarction (AMI); ii) to monitor clinical effects of PBSC mobilization in terms of global and segmental myocardial perfusion and function.

Patients and methods. Eight male patients (mean age: 51,7±5,6 years) were enrolled. All were treated with a primary percutaneous transluminal coronary angioplasty (PTCA) for an anterior (5 patients) or an inferior (3 patients) AMI. The mobilization regimen consisted of G-CSF 5 μg/kg/12h from day 1 to day 3 and GM-CSF 2.5 μg/kg/24h from day 1 to day 5 (starting within 24 hours from PTCA). Since transient severe hypotension was noticed in the first three patients, the protocol was amended by reducing and tapering GM-CSF administration (2.5 μg/kg/24h at days 3, 5, 7). All patients underwent coronary angiography, intracoronary doppler flow study, echocardiography, and nuclear Thallium scan before treatment and at 6 months apart.

Results. WBC and PBSC peaked during the 3^th day of mobilization. Mean WBC and PBSC peaks were 34960± 10794 leukocytes/μL and 29.71± 30.8 CD34+/μL. Five in hospital adverse events were recorded: severe hypotension in 3 patients (as previously mentioned), atrial fybrillation in 1 patient, recurrent ischemia in 1 patients. No death was observed. At present 7 patients completed a 6-months follow-up evaluation: target lesion revascularization rate was 14,3% (1 patient) and target vessel revascularization rate was 42,8% (3 patients). Angiographic mean ejection fraction increased from 49,8±11,9 to57,1±8,9 (p=NS), and mean coronary flow reserve raised from 1,63±0,42 to 2,45±0,36 (p=0,005). Perfusion improvement was observed by nuclear study in 66% of patients.

Conclusions. We conclude that: a) cytokine-induced stem cell mobilization is feasible in AMI patients with adequate GM-CSF administration; b) myocardial perfusion appears to improve within the first six months of follow-up; c) the 3 cases of progressive coronary disease give a concern about a potential negative effect of hematopoietic cytokines (particularly GM-CSF) on silent coronary lesions. However, PBSC mobilization using G-CSF only is worthwhile of further investigation.