Cyclophosphamide-Induced Cyclical Neutropenia: An Animal Model of a Human Periodic Disease

An animal model of a human periodic disease, cyclical neutropenia, was produced in five of nine dogs by administration of a constant daily dose of cyclophosphamide so as to cause mild bone-marrow depression. That this would occur was predicted by a computer model in which granulopoiesis was regarded as being controlled by two feedback loops, one regulating rate of production and the other rate of release of neutrophils. Cyclical neutropenia does not appear to be a specific entity, and its periodicity, and by extension possibly that of other periodic diseases, may be due to the action of feedback control. A hypothetical possibility is that if unrecognized oscillation of blood cell numbers should develop in patients receiving marrow-depressant drugs, estimate of marrow function at any one point of time might give a wrong impression of overall drug effect.