Modelling human granulopoiesis under poly-chemotherapy with G-CSF support.
Cytotoxic drugs administered in polychemotherapy cause a characteristic neutropenic period depending on the schedule of the drugs, which can partly be prevented by G-CSF growth factor support. To quantify these effects and to gain a deeper insight into the dynamics of bone marrow recovery after such suppressing and stimulating disturbances, we construct a biomathematical compartment model of human granulopoiesis under polychemotherapy with G-CSF support. The underlying assumptions and mathematical techniques used to obtain the model are explained in detail. A large variety of biological and clinical data as well as knowledge from a model of murine haematopoiesis are evaluated to construct a physiological model for humans. Particular emphasis is placed on estimating the influence of chemotherapeutic drugs on the granulopoietic system. As a result, we present an innovative method to estimate the bone marrow damage caused by cytotoxic drugs with respect to single identifiable cell stages only on the basis of measured peripheral blood leukocyte dynamics. Conversely, our model can be used in a planning phase of a clinical trial to estimate the haematotoxicity of regimens based on new combinations of drugs already considered and with or without growth factor support.
Scholz
M
M
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Liebigstrasse 27, 04103 Leipzig, Germany. markus.scholz@imise.uni-leipzig.de
Engel
C
C
Loeffler
M
M
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003198:Computer Simulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D051379:Mice; D008875:Middle Aged; D008954:Models, Biological
D016179:Granulocyte Colony-Stimulating Factor