Martínez-Rubio, ÁlvaroChulián, SalvadorBlázquez Goñi, CristinaRamírez Orellana, ManuelPérez Martínez, AntonioNavarro-Zapata, AlfonsoFerreras, CristinaPérez-García, Victor M.Rosa, María2022-12-122022-12-122021-06-14Martínez-Rubio Á, Chulián S, Blázquez Goñi C, Ramírez Orellana M, Pérez Martínez A, Navarro-Zapata A, et al. A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia. Int J Mol Sci. 2021 Jun 14;22(12):6371http://hdl.handle.net/10668/4478Chimeric 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' 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/CAR TMathematical modelAcute lymphoblastic leukemiaB cellBone marrowReceptores quiméricos de antígenosModelos teóricosLeucemia-linfoma linfoblástico de células precursorasSubgrupos de linfocitos BMédula óseaNiñoMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::B-LymphocytesMedical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Bone MarrowMedical Subject Headings::Persons::Persons::Age Groups::ChildMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immunity::Adaptive Immunity::Immunologic MemoryMedical Subject Headings::Diseases::Hemic and Lymphatic Diseases::Lymphatic Diseases::Lymphoproliferative Disorders::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-Lymphoma::Precursor B-Cell Lymphoblastic Leukemia-LymphomaMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment OutcomeMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, AdoptiveMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, BiologicalMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, TheoreticalMedical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocyte Subsets::B-Lymphocyte Subsetsresearch article34198713open access10.3390/ijms221263711422-0067PMC8232108