Consistent bone marrow-derived cell mobilization following repeated short courses of granulocytecolony-stimulating factor in patients with amyotrophic lateral sclerosis: Results from a multicenter prospective trial

Corrado Tarella, Sergio Rutella, Francesca Gualandi, Mario Melazzini, Rosanna Scimè, Mario Petrini, Cristina Moglia, Marco Ulla, Paola Omedé, Vincenzo La Bella, Massimo Corbo, Vincenzo Silani, Gabriele Siciliano, Gabriele Mora, Claudia Caponnetto, Mario Sabatelli, Adriano Chiò

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)50-59
Number of pages10
JournalCytotherapy
Volume12
Issue number1
DOIs
Publication statusPublished - 2010

Keywords

  • Amyotrophic lateral sclerosis
  • Bone marrow-derived stem cells
  • CD34 /CD133 cells
  • Granulocytecolony stimulating factor
  • Mobilization

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Molecular Medicine

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