A Comprehensive Modeling Procedure for the Human Granulopoietic System: Over-all View and Summary of Data

Abstract

Abstract Understanding of the granulopoietic system in both normal and diseased states might be assisted by the use of a quantitative modeling procedure that relates the underlying cellular events of granulopoiesis studied in the laboratory to the marrow and peripheral blood picture as it might be seen in the clinic. In this way, the modeling procedure could become both an adjunct to ongoing laboratory research, as well as a means for rationally deciding on modes of treatment for pathologic conditions. The depth and rapid pace of modern granulopoietic research require that the modeling procedure be, on the one hand, detailed enough to permit the inclusion of the pertinent events at the cellular level as they are known today, while on the other hand, remain flexible enough to permit both the modification of any part and the possibility of seeing the predicted consequences of this modification for both the normal and diseased states. A detailed procedure was developed for an hour-by-hour description of the interrelationship of the kinetics of the various marrow cell types with the events in the peripheral blood and tissue spaces. The model was extended to include the toxic effects of a drug (5-fluorouracil) administered according to the protocol of an actual trial with cancer patients, and the temporal pattern of the predicted effects of the drug on the peripheral blood count was compared with that found in the clinic.