{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:26:45Z","timestamp":1792031205582,"version":"4.4.0"},"reference-count":72,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008545","name":"Asociaci\u00f3n Pablo Ugarte","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100008545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011100","name":"Fundaci\u00f3n Espa\u00f1ola para la Ciencia y la Tecnolog\u00eda","doi-asserted-by":"publisher","award":["UCA PR214"],"award-info":[{"award-number":["UCA PR214"]}],"id":[{"id":"10.13039\/501100011100","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011698","name":"Junta de Comunidades de Castilla-La Mancha","doi-asserted-by":"publisher","award":["SBPLY\/17\/180501\/000154"],"award-info":[{"award-number":["SBPLY\/17\/180501\/000154"]}],"id":[{"id":"10.13039\/501100011698","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006280","name":"Ministerio de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["PID2019- 110895RB-I00"],"award-info":[{"award-number":["PID2019- 110895RB-I00"]}],"id":[{"id":"10.13039\/501100006280","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Inversi\u00f3n Territorial Integrada de la Provincia de C\u00e1diz","award":["ITI-0038-2019"],"award-info":[{"award-number":["ITI-0038-2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients\u2019 experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.<\/jats:p>","DOI":"10.3390\/ijms22126371","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T22:25:46Z","timestamp":1623709546000},"page":"6371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1712-2971","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Mart\u00ednez-Rubio","sequence":"first","affiliation":[{"name":"Department of Mathematics, Universidad de C\u00e1diz, Puerto Real, 11510 C\u00e1diz, Spain"},{"name":"Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA), Hospital Universitario Puerta del Mar, 11009 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5509-5236","authenticated-orcid":false,"given":"Salvador","family":"Chuli\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Universidad de C\u00e1diz, Puerto Real, 11510 C\u00e1diz, Spain"},{"name":"Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA), Hospital Universitario Puerta del Mar, 11009 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4144-2281","authenticated-orcid":false,"given":"Cristina","family":"Bl\u00e1zquez Go\u00f1i","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA), Hospital Universitario Puerta del Mar, 11009 C\u00e1diz, Spain"},{"name":"Department of Pediatric Hematology and Oncology, Hospital de Jerez, 11407 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-6973","authenticated-orcid":false,"given":"Manuel","family":"Ram\u00edrez Orellana","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, Instituto Investigaci\u00f3n Sanitaria La Princesa, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6436-9195","authenticated-orcid":false,"given":"Antonio","family":"P\u00e9rez Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, IdiPAZ, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"Pediatric Hemato-Oncology Department, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5774-8904","authenticated-orcid":false,"given":"Alfonso","family":"Navarro-Zapata","sequence":"additional","affiliation":[{"name":"Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, IdiPAZ, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9595-4998","authenticated-orcid":false,"given":"Cristina","family":"Ferreras","sequence":"additional","affiliation":[{"name":"Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, IdiPAZ, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6575-495X","authenticated-orcid":false,"given":"Victor M.","family":"P\u00e9rez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Mathematical Oncology Laboratory (MOLAB), Instituto de Matem\u00e1tica Aplicada a la Ciencia y la Ingenier\u00eda, Universidad de Castilla-La Mancha, 13005 Ciudad Real, Spain"},{"name":"Departamento de Matem\u00e1ticas, Escuela T\u00e9cnica Superior de Ingenieros Industriales, Universidad de Castilla-La Mancha, 13005 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3069-5651","authenticated-orcid":false,"given":"Mar\u00eda","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Universidad de C\u00e1diz, Puerto Real, 11510 C\u00e1diz, Spain"},{"name":"Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA), Hospital Universitario Puerta del Mar, 11009 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.omtm.2016.12.006","article-title":"Global manufacturing of CAR T cell therapy","volume":"4","author":"Levine","year":"2017","journal-title":"Mol. 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