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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2323-2331. Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2004-01-0306. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0306v1 104/8/2323    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Engel, C. Articles by Loeffler, M. Search for Related Content PubMed PubMed Citation Articles by Engel, C. Articles by Loeffler, M. Related Collections Hematopoiesis and Stem Cells Neoplasia Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS A computational model of human granulopoiesis to simulate the hematotoxic effects of multicycle polychemotherapy Christoph Engel, Markus Scholz, and Markus Loeffler From the Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Germany. Moderate intensification of conventional multicycle chemotherapy has recently been shown to improve treatment results in malignant lymphomas and might prove to be beneficial also in other malignancies. However, the feasibility of such regimens is mainly limited by their granulopoietic toxicity. To identify and quantify the basic cell kinetic mechanisms of damage and stimulation caused by cytotoxic drugs and recombinant human granulocyte colony-stimulating factor (rhG-CSF), respectively, we developed a mathematical model of human granulopoiesis that allows simulation of leukocyte concentration profiles under 10 different multicycle polychemotherapy regimens with varying drug composition, dosage, and scheduling, including rhG-CSF assistance. Clinical data on leukocyte profiles were obtained from large numbers of patients treated within several multicenter trials. Simulation studies show that the leukocyte profiles of all regimens can be appropriately fitted using one single set of assumptions and parameters for the cell kinetic effects of cytotoxic drugs and rhG-CSF. Furthermore, the model can be used to explain the interindividual heterogeneity of hematotoxicity by a differential chemosensitivity, which might be useful in drug scheduling for specific risk groups. It is demonstrated that the model can be used to design and to select new drug schedules for subsequent clinical trial testing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Ziepert, R. Schmits, L. Trumper, M. Pfreundschuh, M. Loeffler, and On behalf of the German High-Grade Non-Hodgkin's L Prognostic factors for hematotoxicity of chemotherapy in aggressive non-Hodgkin's lymphoma Ann. Onc., April 1, 2008; 19(4): 752 - 762. [Abstract] [Full Text] [PDF] I. Roeder, L. M. Kamminga, K. Braesel, B. Dontje, G. de Haan, and M. Loeffler Competitive clonal hematopoiesis in mouse chimeras explained by a stochastic model of stem cell organization Blood, January 15, 2005; 105(2): 609 - 616. [Abstract] [Full Text] [PDF]

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