Persistence of lymphocyte function perturbations after granulocyte–colony-stimulating factor mobilization and cytapheresis in normal peripheral blood stem cell donors

Authors

  • Caroline Marmier-Savet,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Fabrice Larosa,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Faezeh Legrand,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Brigitte Witz,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Mauricette Michallet,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Dana Ranta,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Pascale Louvat,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Marc Puyraveau,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Fabienne Pouthier,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Eric Deconinck,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Pierre Tiberghien,

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author
  • Eric Robinet

    1. From INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon; the Centre d'Investigation Clinique en Biothérapies 506, Besançon; the Hematology Department, University Hospital Besançon, Besançon; the Hematology Department, University Hospital Nancy, Nancy; the Hematology Department, University Hospital Lyon, Lyon; and INSERM, U748, Strasbourg, France.
    Search for more papers by this author

Errata

This article is corrected by:

  1. Errata: ERRATA Volume 51, Issue 5, 1126, Article first published online: 5 May 2011

  • This work was supported by the Agence de la Biomédecine and the Ligue Contre le Cancer, Comité du Doubs. CM is a recipient of a fellowship of Région Franche-Comté and of the Fondation Transplantation (FDTSFV).

Eric Robinet, PhD, INSERM U748, 3 rue Koeberlé, 67000 Strasbourg, France; e-mail: e.robinet@unistra.fr.

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.

STUDY DESIGN AND 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.

CONCLUSION: 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.

Ancillary