Characterization of peripheral blood progenitor cells mobilized by nartograstim (N-terminal replaced granulocyte colony-stimulating factor) in normal volunteers.
We performed an optimal dose-finding study of nartograstim, N-terminal amino acids-replaced rhG-CSF, for mobilization of PBPC in normal volunteers. Nartograstim was injected subcutaneously for 5 days (days 1-5) at a dose of 1 (n = 3), 2 (n = 3), 4 (n = 6) or 8 microg/kg/day (n = 6), and blood samples were obtained by venipuncture on days 1 (pre-treatment), 4, 5 and 6. Nartograstim was well tolerated up to 8 microg/kg/day. Many kinds of PBPC, such as various hematopoietic progenitors in clonal culture, long-term culture-initiating cells (LTC-IC), and CD34+ cells and their primitive subsets (CD33-, HLA-DR-, CD38-) were mobilized in a dose-related manner. At 8 microg/kg/day, the peak number of CD34+ cells and granulocyte-macrophage colony-forming unit (CFU-GM) reached 82.8 x 10(3)/ml and 16.7 x 10(3)/ml, respectively; LTC-ICMiX, which have the capability to produce mixed colony-forming units (CFU-Mix) for over 5 weeks on stromal cells, were detected after the administration of nartograstim. There is a significant relationship between the number of mobilized CD34+ cells and the number of various progenitor cells including LTC-IC. These results indicate that a 5-day administration of nartograstim at 8 microg/kg/day could mobilize PBPC effectively for allografting.
Department of Clinical Oncology, Institute of Medical Science, University of Tokyo, Japan.
K
K
Maruyama
K
K
Tsuji
R
R
Tanaka
K
K
Yamada
Y
Y
Kodera
T
T
Nakahata
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002469:Cell Separation; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000032:analysis; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D007958:Leukocyte Count; D008297:Male; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis; D063268:Sialic Acid Binding Ig-like Lectin 3
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D063268:Sialic Acid Binding Ig-like Lectin 3; D016179:Granulocyte Colony-Stimulating Factor; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; C072115:nartograstim