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.
Acknowledgments
This work was supported in part by grants from: the Ministero Italiano Università e Ricerca (MIUR) (PRIN 2006 and Ricerca locale), Rome, Italy; Regione Piemonte (Ricerca Sanitaria Finalizzata and Ricerca Scientifica Applicata), Torino, Italy; Istituto Superiore di Sanità, Rome, Italy (Malattie Neurodegenerative). G-CSF (Myelostim 34) was kindly provided by Italfarmaco (Milan, Italy).
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.