Administration of daniplestim and granulocyte colony-stimulating factor for the mobilization of hematopoietic progenitor cells in nonhuman primates.

Abstract

We investigated the effects of administering a high-affinity interleukin-3 receptor agonist (daniplestim) and granulocyte colony-stimulating factor (G-CSF) on the mobilization of primitive hematopoietic progenitor cells into peripheral blood (PB). Groups of five rhesus monkeys were treated with 100 mg/kg of daniplestim for 5 days followed by 10 microg/kg of G-CSF for 5 days (D/G), daniplestim and G-CSF administered concurrently for 10 days (D+G), or G-CSF alone for 10 days. Phenotypic PB analysis indicated that the number of CD34+ cells in the G-CSF group had increased to 28 x 10(6)/L by Day 3 and then declined. In contrast, CD34+ cell counts of up to 68 x 10(6)/L were maintained until Day 10 in both the D/G and D+G groups. On Day 5, the total number of colony-forming cells in the PB had increased 15-fold in the D+G group and eightfold in both the D/G group and the G-CSF groups. By Day 7, the numbers of colony-forming units granulocyte/macrophage were comparable in all three groups, and 45-fold increases in the numbers of burst-forming units-erythroid and 12-fold increases in the numbers of multipotent colony-forming units were seen in both the D+G and the D/G groups. The frequency of circulating primitive progenitor cells in long-term stromal cultures was highest with D+G and lowest with G-CSF alone. These results indicate that the combination of daniplestim and G-CSF produces higher and more sustained levels of circulating stem cells than does G-CSF alone. D+G may offer advantages over D/G because it generates more long- and short-term clonogenic cells.