Effects of short-term administration of G-CSF (filgrastim) on bone marrow progenitor cells: analysis of serial marrow samples from normal donors

Abstract

To determine the effect of G-CSF administration on both the total number of CD34⁺ cells and the primitive CD34⁺ subsets in bone marrow (BM), we have analyzed BM samples serially obtained from 10 normal donors in steady-state and during G-CSF treatment. Filgrastim was administered subcutaneously at a dosage of 10 μg/kg/day (n = 7) or 10 μg/kg/12 h (n = 3) for 4 consecutive days. Peripheral blood sampling and BM aspirates were performed on day 1 (just before G-CSF administration), day 3 (after 2 days of G-CSF), and day 5 (after 4 days of G-CSF). During G-CSF administration, a significant increase in the total number of BM nucleated cells was observed. The percentage (range) of CD34⁺ cells decreased in BM from a median of 0.88 (0.47–1.44) on day 1 to 0.57 (0.32–1.87), and to 0.42 (0.16–0.87) on days 3 and 5, respectively. We observed a slight increase in the total number of BM CD34⁺ cells on day 3 (0.66 × 10⁹/l (0.13–0.77)), and a decrease on day 5 (0.23 × 10⁹/l (0.06–1.23)) as compared with steady-state (0.40 × 10⁹/l (0.06–1.68)). The proportion of primitive BM hematopoietic progenitor cells (CD34⁺CD38⁻, CD34⁺HLA-DR⁻, CD34⁺CD117⁻) decreased during G-CSF administration. In parallel, a significant increase in the total number of CD34⁺ cells in peripheral blood was observed, achieving the maximum value on day 5. These results suggest that in normal subjects the administration of G-CSF for 5 days may reduce the number of progenitor cells in BM, particularly the most primitive ones.