A mathematical model of hematopoiesis: II. Cyclical neutropenia

Cyclical neutropenia is a dynamical disease of the hematopoietic system marked by an oscillation in circulating leukocyte (e.g. neutrophil) numbers to near zero levels and then back to normal. This oscillation is also mirrored in the platelets and reticulocytes which oscillate with the same period. Cyclical neutropenia has an animal counterpart in the grey collie. Using the mathematical model of the hematopoietic system of Colijn and Mackey [A mathematical model of hematopoiesis: I. Periodic chronic myelogenous leukemia. Companion paper to the present paper.] we have determined what parameters are necessary to mimic laboratory and clinical data on untreated grey collies and humans, and also what changes in these parameters are necessary to fit data during treatment with granulocyte colony stimulating factor (G-CSF). Compared to the normal steady-state values, we found that the major parameter changes that mimic untreated cyclical neutropenia correspond to a decreased amplification (increased apoptosis) within the proliferating neutrophil precursor compartment, and a decrease in the maximal rate of re-entry into the proliferative phase of the stem cell compartment. For the data obtained during G-CSF treatment, good fits were obtained only when parameters were altered that would imply that G-CSF led to higher amplification (lower rate of apoptosis) in the proliferating neutrophil precursors, and a elevated rate of differentiation into the neutrophil line. r 2005 Elsevier Ltd. All rights reserved.