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In each organ, neutrophils undergo transendothelial migration from vascular to interstitial space, clearance due to apoptosis, and recycling via the lymphatic flow. The model includes cell cycling of progenitor cells in the bone marrow, granulocyte colony\u2010stimulating factor (G\u2010CSF) kinetics and its neutrophil regulatory action, as well as neutrophil margination in the blood. From previously reported studies, <jats:sup>111<\/jats:sup>In\u2010labeled neutrophil kinetic data in the blood and sampled organs were used to estimate the organ trafficking parameters in the model. The model was further developed and evaluated using absolute neutrophil count (ANC), band cell, and segmented neutrophil time course data from healthy volunteers following four dose levels of pegfilgrastim (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.77\u20130.99), along with ANC time course responses following filgrastim (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.96). The baseline values of various cell types in bone marrow and blood, as well as G\u2010CSF concentration in the blood, predicted by the model are consistent with available literature reports. After incorporating the mechanism of action of both paclitaxel and carboplatin, as determined from an <jats:italic>in vitro<\/jats:italic> bone marrow studies, the model reliably predicted the observed ANC time course following paclitaxel plus carboplatin observed in a phase I trial of 46 patients (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.70). The circulatory neutrophil model may provide a mechanistic framework for predicting multi\u2010organ neutrophil homeostasis and dynamics in response to therapeutic agents that target neutrophil dynamics and trafficking in different organs.<\/jats:p>","DOI":"10.1002\/psp4.12620","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T11:55:52Z","timestamp":1617278152000},"page":"671-683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A whole\u2010body circulatory neutrophil model with application to predicting clinical neutropenia from <i>in vitro<\/i> studies"],"prefix":"10.1002","volume":"10","author":[{"given":"Wenbo","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britton","family":"Boras","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development and Medicine San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae","family":"Sung","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development and Medicine San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyue","family":"Hu","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development and Medicine San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Spilker","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development and Medicine San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Z.","family":"D\u2019Argenio","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.04.013"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-688887"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02257"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02739"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12918-014-0138-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00159"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-020-09680-6"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1985.tb02242.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1985.tb02882.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2010.02382.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006288731"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010376966"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","DOI":"10.1208\/s12248-020-00529-x","article-title":"Predicting chemotherapy\u2010induced neutropenia and granulocyte\u2010colony stimulating factor response using model\u2010based in vitro to clinical translation","volume":"22","author":"Chen W","year":"2020","journal-title":"AAPS J"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-019-03960-w"},{"key":"e_1_2_9_16_1","unstructured":"National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. 2009. 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