A mathematical model of white blood cell dynamics during maintenance therapy of childhood acute lymphoblastic leukemia

Le TT, Jost F, Raupach T, Zierk J, Rauh M, Suttorp M, Stanulla M, Metzler M, Sager S (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Mathematical Medicine and Biology Oxford University Press

Book Volume: 36

Pages Range: 471-488

Journal Issue: 4

DOI: 10.1093/imammb/dqy017

Abstract

Acute lymphoblastic leukemia is the most common malignancy in childhood and requires prolonged oral maintenance chemotherapy to prevent disease relapse after remission induction with intensive intravenous chemotherapy. In maintenance therapy, drug doses of 6-mercaptopurine (6-MP) and methotrexate (MTX) are adjusted to achieve sustained antileukemic activity without excessive myelosuppression. However, uncertainty exists regarding timing and extent of drug dose responses and optimal dose adaptation strategies. We propose a novel comprehensive mathematical model for 6-MP and MTX pharmacokinetics, pharmacodynamics and myelosuppression in acute lymphoblastic maintenance therapy. We personalize and cross-validate the mathematical model using clinical data and propose a real-time algorithm to predict chemotherapy responses with a clinical decision support system as a potential future application.

Authors with CRIS profile

Thomas Simmerl Department of Paediatrics and Adolescent Medicine Jakob Zierk Department of Paediatrics and Adolescent Medicine Manfred Rauh Department of Paediatrics and Adolescent Medicine Markus Metzler Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE)

How to cite

APA:

Le, T.T., Jost, F., Raupach, T., Zierk, J., Rauh, M., Suttorp, M.,... Sager, S. (2019). A mathematical model of white blood cell dynamics during maintenance therapy of childhood acute lymphoblastic leukemia. Mathematical Medicine and Biology, 36(4), 471-488. https://doi.org/10.1093/imammb/dqy017

MLA:

Le, Thuy T.T., et al. "A mathematical model of white blood cell dynamics during maintenance therapy of childhood acute lymphoblastic leukemia." Mathematical Medicine and Biology 36.4 (2019): 471-488.

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