title: 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: 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.
authors.affiliation: Dip Medicina-Oncologia Sperimentale, SC Universitaria di Ematologia and Molecular Biotechnology Center, Torino, Italy. corrado.tarella@unito.it
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.forename: Mario
authors.initials: M
authors.lastname: Melazzini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Scimè
authors.forename: Mario
authors.initials: M
authors.lastname: Petrini
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.forename: Marco
authors.initials: M
authors.lastname: Ulla
authors.forename: Paola
authors.initials: P
authors.lastname: Omedé
authors.forename: Vincenzo La
authors.initials: VL
authors.lastname: Bella
authors.forename: Massimo
authors.initials: M
authors.lastname: Corbo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.forename: Claudia
authors.initials: C
authors.lastname: Caponnetto
authors.forename: Mario
authors.initials: M
authors.lastname: Sabatelli
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
mesh_terms: 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
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor