Changes of cytokine levels during granulocyte-colony-stimulating factor stem cell mobilization in healthy donors: association with mobilization efficiency and potential predictive significance.
BACKGROUND
Peripheral blood stem cells are an important source of hematopoietic stem cells (HSCs) for allogeneic transplantations. Some allogeneic donors mobilize HSCs poorly in response to the granulocyte--colony-stimulating factor (G-CSF). The estimation of the mobilization result in an individual donor is difficult due to the absence of suitable predictive factors.


METHODS
We analyzed the concentrations and kinetics of certain cytokines induced by G-CSF in 76 healthy donors and compared them with the mobilization efficiency.


RESULTS
The levels of the most cytokines increased after the G-CSF application: sICAM, sVCAM, MMP-9, interleukin (IL)-6, TNF-α, sE-selectin, and fibronectin. The concentrations of SDF-1α and IL-8 decreased and VEGF and fractalkine remained unchanged. The premobilization concentrations of IL-6 (p = 0.0093) and TNF-a (p = 0.0006) correlated with preapheresis CD34+ cell count. The comparison of premobilization cytokine levels between better and worse mobilizers showed a difference for TNF-α (p = 0.0006) and IL-6 (p = 0.0682). The TNF-α level below cutoff of 3.6 pg/mL implied approximately 20 times higher risk of poor mobilization (odds ratio, 19.9; p = 0.0002). The immunophenotyping of CD34+ cells suggested a negative correlation between Day +5 CD34+ count and expression of CD11a (p = 0.0319) and a positive correlation with CD44 antigen expression (p = 0.0096).


CONCLUSIONS
The concentrations of certain cytokines corresponded to the quality of HSC mobilization in healthy donors. Their levels measured before mobilization could probably serve as predictive factors for mobilization efficacy and prospectively detect donors who might profit from new mobilization molecules.
Lysák
Daniel
D
Department of Hematology and Oncology, University Hospital Pilsen, Czech Republic, Czech National Marrow Donor Registry (CS2). lysak@fnplzen.cz
Hrabětová
Marcela
M
Vrzalová
Jindra
J
Koza
Vladimír
V
Navrátilová
Jana
J
Svoboda
Tomáš
T
Jungová
Alexandra
A
Topolčan
Ondřej
O
D000328:Adult; D001772:Blood Cell Count; D001782:Blood Donors; D016207:Cytokines / Q000097:blood*; D046148:Donor Selection; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D011994:Recombinant Proteins; D013997:Time Factors; D055815:Young Adult
D016207:Cytokines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim