Sequential versus concurrent administration of daniplestim and g-csf for the mobilization of hematopoietic progenitors in non-human primates

We investigated the effects of "priming" primitive hematopoietic progenitor cells (HP) with a high affinity IL-3 receptor agonist (daniplestim) followed by G-CSF administration on the number of HP in the peripheral blood (PB). Groups of 5 monkeys were treated with either i) daniplestim alone (100 jag/kg/day) for 5 days followed by G-CSF (10 ng/kg/day) for 5 days (D/G-CSF) or ii) daniplestim and G-CSF given concurrently for 10 days (D+G-CSF) or iii) G-CSF alone. At 5 days, the PB neutrophil and mononuclear count in the D/G-CSF group remained unchanged, while an 8-fold increase in neutrophils and a 1.5-fold increase in mononuclear cells was observed in the D+G-CSF and G-CSF groups. Analysis of the PB indicated the number CD34+ cells increased to 28 per pi until day 3 and then declined in the G-CSF group. In contrast, CD34+ cell counts of up to 68 per ul were maintained until day 10 in both the D/G-CSF and D+GCSF groups. The functional activity of HP was measured in a methylcellulose assay. By day 5, the total colony-forming cells (CFC) in the PB increased 15-fold in the D+G-CSF group, 8-fold in the D/GCSF group and 5-fold in the G-CSF group. On day 7, while the CFUGM were comparable in all 3 groups, 45-fold increases in BFUe and 12-fold increases in CFU-GEMM were detected in both the D+G-CSF and D/G-CSF groups compared to G-CSF. To quantitate early HP, the frequency of PB cells giving rise to colonies in stromal cultures was determined. Maximal increases of 4-fold (D+G-CSF), 2-fold D/GCSF, 1.6-fold (G-CSF) were observed. These results indicate that both concurrent or sequential treatment with daniplestim and G-CSF more effectively mobilizes HP into the peripheral blood than G-CSF treatment alone.