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.
OBJECTIVE
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 microg/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/microL, 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.
Tarella
Corrado
C
Dip Medicina-Oncologia Sperimentale, SC Universitaria di Ematologia and Molecular Biotechnology Center, Torino, Italy. corrado.tarella@unito.it
Rutella
Sergio
S
Gualandi
Francesca
F
Melazzini
Mario
M
Scimè
Rosanna
R
Petrini
Mario
M
Moglia
Cristina
C
Ulla
Marco
M
Omedé
Paola
P
Bella
Vincenzo La
VL
Corbo
Massimo
M
Silani
Vincenzo
V
Siciliano
Gabriele
G
Mora
Gabriele
G
Caponnetto
Claudia
C
Sabatelli
Mario
M
Chiò
Adriano
A
D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D003114:Colony-Forming Units Assay; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011446:Prospective Studies; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D018952:Antigens, CD34; D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor