B cell chronic lymphocytic leukemia - A model with immune response

Abstract

B cell chronic lymphocytic leukemia (B-CLL) is known to have substantial clinical heterogeneity. There is no cure, but treatments allow for disease management. However, the wide range of clinical courses experienced by B-CLL patients makes prognosis and hence treatment a significant challenge. In an attempt to study disease progression across different patients via a unified yet flexible approach, we present a mathematical model of B-CLL with immune response, that can capture both rapid and slow disease progression. This model includes four different cell populations in the peripheral blood of humans: B-CLL cells, NK cells, cytotoxic T cells and helper T cells. We analyze existing data in the medical literature, determine ranges of values for parameters of the model, and compare our model outcomes to clinical patient data. The goal of this work is to provide a tool that may shed light on factors affecting the course of disease progression in patients. This modeling tool can serve as a foundation upon which future treatments can be based.

A Personalized Framework for Dynamic Modeling of Disease Trajectories in Chronic Lymphocytic Leukemia

“…For example, immunophenotyping to distinguish between B-and Tcells in the peripheral blood lymphocyte compartment [41,45] which may facilitate the incorporation of immune interactions and current immuno-chemotherapeutic targets [46]. Our model therefore complements the 1-compartment model of Nanda et al [43]. If we could assume data on T-cell populations, i.e., CD4+, CD8+, the Nanda et al [43] model could replace each G0 model in Fig.…”

“…Our model therefore complements the 1-compartment model of Nanda et al [43]. If we could assume data on T-cell populations, i.e., CD4+, CD8+, the Nanda et al [43] model could replace each G0 model in Fig. 1.…”

“…One of the earliest mathematical frameworks of CLL models the interaction between CLL cells and T-cells, a component of the microenvironment, via a Volterra predator-prey equation [42]. A kinetic model [30] has also been used to develop the first model of CLL incorporating interactions between CLL cells, natural killer (NK) cells, cytotoxic (CD8+) T-cells and helper (CD4+) T-cells [43]. This model implicitly as- sumes that the entire body is 1-compartment and thereby does not account for the proliferation center microenvironment, disease center carrying capacity, or the cellular migration between disease centers [43].…”

“…A kinetic model [30] has also been used to develop the first model of CLL incorporating interactions between CLL cells, natural killer (NK) cells, cytotoxic (CD8+) T-cells and helper (CD4+) T-cells [43]. This model implicitly as- sumes that the entire body is 1-compartment and thereby does not account for the proliferation center microenvironment, disease center carrying capacity, or the cellular migration between disease centers [43]. CLL lymphocytosis kinetics have been studied using a 2-compartment model [30] that characterizes CLL cell redistribution dynamics from proliferation centers into the peripheral blood induced by the novel BTK inhibitor, Ibrutinib albeit there is little known about steady-state dynamics or of that which occurs during the natural course of disease [44].…”

Mathematical analysis of a B-cell chronic lymphocytic leukemia model with immune response

“…In [1] a thorough study of B-cell chronic lymphocytic leukemia (B-CLL) has been undertaken by means of a highly nonlinear mathematical model based on ordinary differential equations. The relevance of this investigation is apparent from the realistic situations that have been scrutinized via numerical simulations, based on published data of B-CLL patients.…”