The Effectiveness of B Cells in CAR T Cell Therapy for B Cells Acute Lymphoblastic Leukemia

Elena M. D. P. Haries, Abadi Abadi

Abstract


Chimeric Antigen Receptor (CAR) T cell therapy has shown remarkable clinical outcomes in B cell Acute Lymphoblastic Leukemia (B-ALL). The treatment can utilize the immune system to recognize and kill leukemia cells through the CD19 antigen target.  However, the CD19 antigen is also expressed on normal B cells, which can cause side effects in B cell aplasia.  This study modifies a mathematical model of the interaction between CAR T cells, leukemia cells, and normal B cells by introducing the assumption that leukemia cells follow logistic growth dynamics. Determined the equilibrium point and continues to analyze stability using linearization and the Routh-Hurwitz criterion.  The analysis reveals four equilibrium points, including a state where leukemia cells grow at maximum capacity in the absence of CAR T cells.  Bifurcation analysis shows the occurrence of both transcritical and subcritical Hopf bifurcations, with distinct patterns compared to previous models.   A heteroclinic cycle was also identified, indicating that relapse may occur even after remission.   The logistic growth and B cell progenitors not only shape remission and relapse dynamics but also explain the dual role of B cells in sustaining CAR T activation and causing complications such as Cytokine Release Syndrome (CRS). This provides new insights for understanding therapy outcomes and optimizing CAR T cell treatment strategies.

Keywords


Leukemia, B cell; CAR T cell therapy; Stability analysis; Bifurcation

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DOI: https://doi.org/10.37905/jjbm.v6i3.32511

Copyright (c) 2025 Elena M. D. P. Haries, Abadi Abadi

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