TY - JOUR
T1 - Consistent bone marrow-derived cell mobilization following repeated short courses of granulocytecolony-stimulating factor in patients with amyotrophic lateral sclerosis
T2 - Results from a multicenter prospective trial
AU - Tarella, Corrado
AU - Rutella, Sergio
AU - Gualandi, Francesca
AU - Melazzini, Mario
AU - Scimè, Rosanna
AU - Petrini, Mario
AU - Moglia, Cristina
AU - Ulla, Marco
AU - Omedé, Paola
AU - Bella, Vincenzo La
AU - Corbo, Massimo
AU - Silani, Vincenzo
AU - Siciliano, Gabriele
AU - Mora, Gabriele
AU - Caponnetto, Claudia
AU - Sabatelli, Mario
AU - Chiò, Adriano
PY - 2010
Y1 - 2010
N2 - 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 granulocytecolony 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 4157/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.
AB - 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 granulocytecolony 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 4157/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.
KW - Amyotrophic lateral sclerosis
KW - Bone marrow-derived stem cells
KW - CD34 /CD133 cells
KW - Granulocytecolony stimulating factor
KW - Mobilization
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U2 - 10.3109/14653240903300682
DO - 10.3109/14653240903300682
M3 - Article
C2 - 19878077
AN - SCOPUS:75449087365
VL - 12
SP - 50
EP - 59
JO - Cytotherapy
JF - Cytotherapy
SN - 1465-3249
IS - 1
ER -