The effect of continuous G‐CSF application in human cyclic neutropenia: a model analysis

Publisher Website
Google Scholar
Abstract
Human cyclic neutropenia (CN) is a rare haematological disorder characterized by oscillations of blood neutrophils at subnormal levels with a stable period of approximately 21 d. During the phase of severe neutropenia (neutrophils <250 cells/yul), which last 4–10 d, the patients are endangered by serious infections. Several authors report that continuous G‐CSF application can elevate the blood neutrophils to such a level that the risk of infections is significantly reduced. Although the characteristic cycles are not eliminated by G‐CSF, the period of the oscillations is shortened to 12–14 d. Based on a previously proposed computer‐simulation model of human CN, the effects of continuous G‐CSF application on CN are studied. It is shown how the known different cell‐kinetic effects of G‐CSF on granulopoiesis explain the clinical data in CN. The reduced length of the cycles emerges as a result of the transit time reduction of the post‐mitotic granulopoietic cells by G‐CSF. The measured increase of the neutrophil maxima is reproduced by the additional mitoses of the immature granulopoietic bone marrow cells induced by G‐CSF. The slight elevation of the neutrophil nadirs can be attributed to a weak effect of G‐CSF on the assumed underlying defect in CN (an abnormally small variance of the granulopoietic bone‐marrow transit time).