Characterization of peripheral blood progenitor cells mobilized by nartograstim (N-terminal replaced granulocyte colony-stimulating factor) in normal volunteers

Abstract

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 μg/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 μg/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 μg/kg/day, the peak number of CD34⁺ cells and granulocyte–macrophage colony-forming unit (CFU-GM) reached 82.8 × 10³/ml and 16.7 × 10³/ml, respectively; LTC-IC_Mix, 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 μg/kg/day could mobilize PBPC effectively for allografting.