Quantification of the cell kinetic effects of G-CSF using a model of human granulopoiesis

Using a mathematical model of normal human granulopoiesis, the most important influences of granulocyte colony-stimulating factor (G-CSF) on the regulation of white cell production can be quantified. G-CSF increases the blood neutrophils via three effects: reduction of the transit time of the postmitotic granulopoietic bone marrow cells; additional mitoses of the early granulopoietic bone marrow cells; and possibly demargination. The application of G-CSF in vivo results in a summation of the single effects. For a G-CSF application of 5 days at a daily dose of 10 micrograms/kg, the reduction of postmitotic bone marrow transit time from 6 days to 1.5 days together with demargination with a rate of 10% per hour explains the initial increase of the blood neutrophils until day 1. Both effects fail to explain the sustained increase thereafter. Enhanced amplification of the early granulopoietic bone marrow cells is also necessary to reproduce the sustained increase. Depending on the individual clinical data, approximately 5 additional mitoses occur, evenly distributed to the myeloblasts, promyelocytes and myelocytes. If the above three effects of G-CSF are assumed, the model predicts bone marrow data in accordance with clinical observations.