Consistent bone marrow-derived cell mobilization following repeated short courses of granulocyte-colony-stimulating factor in patients with amyotrophic lateral sclerosis: results from a multicenter prospective trial.

Background and aims. The aim of this study was to evaluate and characterize the feasibility and safety of bone marrowderived cell (BMC) mobilization following repeated courses of granulocyte–colony stimulating factor (G-CSF) in patients with amyotrophic lateral sclerosis (ALS). Methods. Between January 2006 and March 2007, 26 ALS patients entered a multicenter trial that included four courses of BMC mobilization at 3-month intervals. In each course, G-CSF (5 μg/kg b.i.d.) was administered for four consecutive days; 18% mannitol was also given. Mobilization was monitored by fl ow cytometry analysis of circulating CD34+ cells and by in vitro colony assay for clonogenic progenitors. Co-expression by CD34+ cells of CD133, CD90, CD184, CD117 and CD31 was also assessed. Results. Twenty patients completed the four-course schedule. One patient died and one refused to continue the program before starting the mobilization courses; four discontinued the study protocol because of disease progression. Overall, 89 G-CSF courses were delivered. There were two severe adverse events: one prolactinoma and one deep vein thrombosis. There were no discontinuations as a result of toxic complications. Circulating CD34+ cells were monitored during 85 G-CSF courses and were always markedly increased; the range of median peak values was 41–57/μL, with no signifi cant differences among the four G-CSF courses. Circulating clonogenic progenitor levels paralleled CD34+ cell levels. Most mobilized CD34+ cells co-expressed stem cell markers, with a signifi cant increase in CD133 co-expression. Conclusions. It is feasible to deliver repeated courses of G-CSF to mobilize a substantial number of CD34+ cells in patients with ALS; mobilized BMC include immature cells with potential clinical usefulness.