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

Abstract Background and aims The aim of this study was to evaluate and characterize the feasibility and safety of bone marrow-derived 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 flow 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 significant 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 significant 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.