Persistence of lymphocyte function perturbations after granulocyte-colony-stimulating factor mobilization and cytapheresis in normal peripheral blood stem cell donors.
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.
Marmier-Savet
Caroline
C
INSERM, Université de Franche-Comte, IFR133, and Etablissement Français du Sang, Bourgogne/Franche-Comté, UMR 645, Besançon, France.
Larosa
Fabrice
F
Legrand
Faezeh
F
Witz
Brigitte
B
Michallet
Mauricette
M
Ranta
Dana
D
Louvat
Pascale
P
Puyraveau
Marc
M
Raus
Nicole
N
Tavernier
Maribel
M
Mathieu-Nafissi
Suzanne
S
Hequet
Olivier
O
Pouthier
Fabienne
F
Deconinck
Eric
E
Tiberghien
Pierre
P
Robinet
Eric
E
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
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor