ArticleCPT: pharmacometrics & systems pharmacology2019
Quantifying Drug-Induced Bone Marrow Toxicity Using a Novel Haematopoiesis Systems Pharmacology Model.
Article in CPT: pharmacometrics & systems pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Prediction of neutrophil nadir and recovery following paediatric haematopoietic cell transplantation with busulfan conditioning.British journal of clinical pharmacology · 2026Article
- Efficacy of Poloxamer 188 in Experimental Myelosuppression Model Induced by Carboplatin in CBA Mice.International journal of molecular sciences · 2025Article
- Are the Common Genetic 3'UTR Variants in ADME Genes Playing a Role in Tolerance of Breast Cancer Chemotherapy?International journal of molecular sciences · 2024Article
- Chemotherapy-induced thrombocytopenia: literature review.Discover oncology · 2023Review
- Quantitative Systems Pharmacology Modeling of Avadomide-Induced Neutropenia Enables Virtual Clinical Dose and Schedule Finding Studies.The AAPS journal · 2021Article
- Systems Modeling to Quantify Safety Risks in Early Drug Development: Using Bifurcation Analysis and Agent-Based Modeling as Examples.The AAPS journal · 2021Review
- Predicting Chemotherapy-Induced Neutropenia and Granulocyte Colony-Stimulating Factor Response Using Model-Based In Vitro to Clinical Translation.The AAPS journal · 2020Article
- Importance of Stability Analysis When Using Nonlinear Semimechanistic Models to Describe Drug-Induced Hematotoxicity.CPT: pharmacometrics & systems pharmacology · 2020Article
- An in vitro quantitative systems pharmacology approach for deconvolving mechanisms of drug-induced, multilineage cytopenias.PLoS computational biology · 2020Article
- A physiological model of granulopoiesis to predict clinical drug induced neutropenia from in vitro bone marrow studies: with application to a cell cycle inhibitor.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Model-Based Simulation of Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia.Frontiers in physiology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Haematological toxicity associated with cancer therapeutics is monitored by changes in blood cell count, and their primary effect is on proliferative progenitors in the bone marrow. Using observations in rat bone marrow and blood, we characterize a mathematical model that comprises cell proliferation and differentiation of the full haematopoietic phylogeny, with interacting feedback loops between lineages in homeostasis as well as following carboplatin exposure. We accurately predicted the temporal dynamics of several mature cell types related to carboplatin-induced bone marrow toxicity and identified novel insights into haematopoiesis. Our model confirms a significant degree of plasticity within bone marrow cells, with the number and type of both early progenitors and circulating cells affecting cell balance, via feedback mechanisms, through fate decisions of the multipotent progenitors. We also demonstrated cross-species translation of our predictions to patients, applying the same core model structure and considering differences in drug-dependent and physiology-dependent parameters.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.