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, Victor M.
A1 Rosa, María
K1 CAR T
K1 Mathematical model
K1 Acute lymphoblastic leukemia
K1 B cell
K1 Bone marrow
K1 Receptores quiméricos de antígenos
K1 Modelos teóricos
K1 Leucemia-linfoma linfoblástico de células precursoras
K1 Subgrupos de linfocitos B
K1 Médula ósea
K1 Niño
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
YR 2021
FD 2021-06-14
LK http://hdl.handle.net/10668/4478
UL http://hdl.handle.net/10668/4478
LA en
NO Martínez-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):6371
DS RISalud
RD Apr 20, 2025