Kinetics of G-CSF and CD34+ cell mobilization after once or twice daily stimulation with rHu granulocyte-stimulating factor (lenograstim) in healthy volunteers: an intraindividual crossover study.
BACKGROUND
G-CSF given as split dose increased the harvested number of CD34+ cells in comparison to a once daily schedule, but the mechanism is poorly understood.


METHODS
To investigate the schedule dependency of G-CSF in healthy volunteers with respect to CD34+ cell mobilization, the same dose of G-CSF was applied in four healthy volunteers in two different schedules (once daily vs. split doses twice daily) in a crossover design after a washout period of 3 months. CD34+ cell kinetics in serum were determined as well as G-CSF serum kinetics on Days 1 and 4 after stimulation.


RESULTS
In all volunteers, the twice daily schedule led to a higher CD34+ cell count after 4 days of G-CSF stimulation (median, 94.5 vs. 47/ microL; p = 0.05). On Days 1 and 4, there was a higher peak serum concentration of G-CSF serum level after the once daily application (15,175 vs. 6,859 pg/mL and 7440 vs. 2388 pg/mL, respectively) than after the twice daily schedule. In contrast, after the once daily application the minimum serum level of G-CSF serum level was lower than after the twice daily schedule (663 vs. 1361 pg/mL and 246 vs. 441 pg/mL, respectively). No difference of area under the curve for G-CSF was observed on Days 1 and 4 after G-CSF stimulation.


CONCLUSIONS
It is suggested that application of G-CSF twice daily leads to a higher CD34+ cell mobilization owing to a higher minimum serum level and therefore to a more continuous serum baseline level resulting in a more efficient CD34+ cell mobilization.
Kröger
Nicolaus
N
Department of Bone Marrow Transplantation, University-Hospital Hamburg-Eppendorf, Hamburg, Germany. nkroeger@uke.uni-hamburg.de
Sonnenberg
Stefan
S
Cortes-Dericks
Lourdes
L
Freiberger
Petra
P
Mollnau
Hanke
H
Zander
Axel R
AR
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism*; D003114:Colony-Forming Units Assay; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000097:blood*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007700:Kinetics; D000078224:Lenograstim; D007958:Leukocyte Count; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage*; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D018952:Antigens, CD34; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim