title: Persistence of lymphocyte function perturbations after granulocyte-colony-stimulating factor mobilization and cytapheresis in normal peripheral blood stem cell donors.
abstract: BACKGROUND
  The short-term effects of granulocyte-colony-stimulating factor (G-CSF) have been extensively studied, but recent reports of G-CSF-induced genetic perturbations raised concerns regarding its long-term safety. In this respect, duration of G-CSF-induced perturbations has been less studied than short-term effects and needs to be evaluated.
  
  
  METHODS
  G-CSF mobilization-induced immunologic alterations were prospectively analyzed in a cohort of 24 healthy donors. Blood samples were taken before G-CSF administration; at the time of administration; and at 1, 3, 6, and 12 months and analyzed for blood cell counts and in vitro cytokines (interleukin [IL]-2, -8, and -10) and immunoglobulin production, quantified in the culture supernatant of peripheral blood mononuclear cells (PBMNCs) after, respectively, phytohemagglutinin and pokeweed mitogen stimulation.
  
  
  RESULTS
  Platelet, granulocyte, monocyte, B, and dendritic blood cell counts as well as the IL-2, -8, and -10 secretion by PBMNCs, perturbed at the time of G-CSF mobilization, returned to baseline values at 1 month, with T-cell and natural killer cell counts recovering at 3 months. In vitro immunoglobulin production was increased up to 6 months after mobilization.
  
  
  CONCLUSIONS
  Although assessment of the potential long-term risk of G-CSF administration will require prolonged observation of larger cohorts, our data show that the duration of immunologic perturbations may be more persistent than previously anticipated, especially for B-cell functional alterations. Most perturbations remain, however, transient with a return to baseline values within 1 year.
authors.affiliation: INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Marmier-Savet
authors.forename: Fabrice
authors.initials: F
authors.lastname: Larosa
authors.forename: Faezeh
authors.initials: F
authors.lastname: Legrand
authors.forename: Brigitte
authors.initials: B
authors.lastname: Witz
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Dana
authors.initials: D
authors.lastname: Ranta
authors.forename: Pascale
authors.initials: P
authors.lastname: Louvat
authors.forename: Marc
authors.initials: M
authors.lastname: Puyraveau
authors.forename: Nicole
authors.initials: N
authors.lastname: Raus
authors.forename: Maribel
authors.initials: M
authors.lastname: Tavernier
authors.forename: Suzanne
authors.initials: S
authors.lastname: Mathieu-Nafissi
authors.forename: Olivier
authors.initials: O
authors.lastname: Hequet
authors.forename: Fabienne
authors.initials: F
authors.lastname: Pouthier
authors.forename: Eric
authors.initials: E
authors.lastname: Deconinck
authors.forename: Pierre
authors.initials: P
authors.lastname: Tiberghien
authors.forename: Eric
authors.initials: E
authors.lastname: Robinet
mesh_terms: D000328:Adult; D001782:Blood Donors; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007154:Immune System Diseases / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D007937:Leukapheresis / Q000379:methods*; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D020127:Recovery of Function / Q000276:immunology; D013997:Time Factors; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor