Recombinant human granulocyte-colony stimulating factor: in vivo effects on myelopoiesis in primates.

Overview

G-CSF belongs to a family of hematopoietic growth factors, also known as colony stimulating factors. It supports the growth and differentiation of predominantly committed neutrophil precursors and activates the function of peripheral blood neutrophils in vitro. In vivo studies in primates (Cynomolgus monkeys) demonstrated that G-CSF is a potent myeloid growth and differentiation factor causing a dose-dependent increase predominantly in the peripheral blood neutrophils. To assess the effects of G-CSF in chemotherapy induced cytopenias, we administered G-CSF to monkeys that had been treated with cyclophosphamide (60 mg/kg/dx2), or repeated cycles of busulfan (4, 6 or 10 mg/kg/dx3). In both, cyclophosphamide and busulfan induced myelosuppression, G-CSF in doses between 10 and 30 micrograms/kg/d was able to significantly shorten the time of neutropenia. In addition, monkeys were treated with G-CSF (50 or 100 micrograms/kg/d) for one month post autologous bone marrow transplantation following total body irradiation. The time of neutropenia (less than 1,000 neutrophils/mm3) was shorter in the G-CSF treated monkeys (10 days in the 100 micrograms/kg/d treated monkey) compared to two controls (21 days). The post transplant absolute neutrophil count of approximately 30,000/mm3 could be maintained for the entire period of G-CSF exposure.