RT journal article
T1 A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia
A1 Martínez Rubio, Álvaro
A1 Chulián, Salvador
A1 Blázquez Goñi, Cristina
A1 Ramírez-Orellana, Manuel
A1 Pérez Martínez, Antonio
A1 Navarro Zapata, Alfonso
A1 Ferreras, Cristina
A1 Pérez-García, Víctor M.
A1 Rosa Durán, María
A2 Matemáticas
K1 CAR T
K1 mathematical model
K1 acute lymphoblastic leukemia
K1 B cell
K1 bone marrow
AB 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' 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.
PB MDPI
SN 1422-0067
YR 2021
FD 2021-06
LK http://hdl.handle.net/10498/25459
UL http://hdl.handle.net/10498/25459
LA eng
NO This work was partially supported by the Fundacion Espanola para la Ciencia y la Tecnologia (UCA PR214), the Asociacion Pablo Ugarte (APU, Spain), Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000154), Ministry of Science and Technology, Spain (PID2019110895RB-I00), and Inversion Territorial Integrada de la Provincia de Cadiz (ITI-0038-2019).
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-may-2026