scholarly journals Personalized Immunotherapy Treatment Strategies for a Dynamical System of Chronic Myelogenous Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2030
Author(s):  
Paul A. Valle ◽  
Luis N. Coria ◽  
Corina Plata
Keyword(s):  
Dynamical System ◽  
Cancer Cells ◽  
Chronic Myelogenous Leukemia ◽  
Sufficient Conditions ◽  
Treatment Strategies ◽  
Myelogenous Leukemia ◽  
Invariant Sets ◽  
Cellular Immunotherapy ◽  
Complete Eradication ◽  
Treatment Parameter

This paper is devoted to exploring personalized applications of cellular immunotherapy as a control strategy for the treatment of chronic myelogenous leukemia described by a dynamical system of three first-order ordinary differential equations. The latter was achieved by applying both the Localization of Compact Invariant Sets and Lyapunov’s stability theory. Combination of these two approaches allows us to establish sufficient conditions on the immunotherapy treatment parameter to ensure the complete eradication of the leukemia cancer cells. These conditions are given in terms of the system parameters and by performing several in silico experimentations, we formulated a protocol for the therapy application that completely eradicates the leukemia cancer cells population for different initial tumour concentrations. The formulated protocol does not dangerously increase the effector T cells population. Further, complete eradication is considered when solutions go below a finite critical value below which cancer cells cannot longer persist; i.e., one cancer cell. Numerical simulations are consistent with our analytical results.

scholarly journals Novel Treatment Strategies Utilizing Immune Reactions against Chronic Myelogenous Leukemia Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5435
Author(s):  
Maiko Matsushita
Keyword(s):  
Stem Cells ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitors ◽  
Treatment Strategies ◽  
Myelogenous Leukemia ◽  
Novel Treatment ◽  
Car T ◽  
Treatment Free Remission ◽  
Novel Treatment Strategies ◽  
Patients Experience

Introduction of tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myelogenous leukemia (CML), and treatment-free remission (TFR) is now a treatment goal. However, about half of the patients experience molecular relapse after cessation of TKIs, suggesting that leukemic stem cells (LSCs) are resistant to TKIs. Eradication of the remaining LSCs using immunotherapies including interferon-alpha, vaccinations, CAR-T cells, and other drugs would be a key strategy to achieve TFR.

Determinants of prognosis in late chronic-phase chronic myelogenous leukemia.

1998 ◽  
Vol 16 (12) ◽  
pp. 3782-3787 ◽  
Author(s):  
J Rodriguez ◽  
J Cortes ◽  
T Smith ◽  
S O'Brien ◽  
M B Rios ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Risk Group ◽  
Performance Status ◽  
Treatment Strategies ◽  
Chronic Phase ◽  
Poor Performance ◽  
Albumin Level ◽  
Myelogenous Leukemia ◽  
Poor Performance Status ◽  
Staging Model

PURPOSE Since interferon alfa (IFN-A) became an established treatment in chronic myelogenous leukemia (CML), more patients are referred to tertiary centers in late chronic phase (ie, > 12 months after diagnosis). Trials conducted in this phase cannot be evaluated precisely unless the features that determine prognosis in late chronic-phase CML are identified. The purpose of this study is to define the prognostic determinants of late chronic-phase CML. PATIENTS AND METHODS From 1980 to 1997,257 consecutive CML patients referred in late chronic phase were studied. Their clinical characteristics at the time of referral and their association with survival were investigated. A staging model was designed. RESULTS The median survival from time of referral was 43 months. Pretreatment characteristics associated with worse outcome included older age, poor performance status, splenomegaly, low albumin level, high percentage of blasts or basophils in peripheral blood (PB) or bone marrow, longer duration of chronic phase, and poor-risk group as defined by the Synthesis model. Prior exposure to IFN-A was not associated with worse outcome. By multivariate analysis, characteristics associated with shorter survival were age of 60 years or older, time from diagnosis of 3 years or greater, performance status of 1 or greater, PB basophils of 7% or greater, spleen 10 cm or greater, PB blasts 3% or greater, and albumin level less than 4 g/dL. A model that included age, duration of chronic phase, performance status, and PB basophils was generated. Patients with no, one, two, or three or greater adverse factors had median survivals of 71, 49, 26, and 19 months, respectively. CONCLUSION A staging model for late chronic-phase CML can stratify patients in four groups with significantly different outcomes. If confirmed in independent populations, such a model could be considered in the analysis of future trials of treatment strategies in late chronic-phase CML.

scholarly journals Bounded Motions of the Dynamical Systems Described by Differential Inclusions

2009 ◽  
Vol 2009 ◽  
pp. 1-9
Author(s):  
Nihal Ege ◽  
Khalik G. Guseinov
Keyword(s):  
Dynamical System ◽  
Dynamical Systems ◽  
Differential Inclusion ◽  
Differential Inclusions ◽  
Sufficient Conditions ◽  
Invariant Sets ◽  
Control Vector ◽  
Upper Semicontinuous ◽  
Right Hand ◽  
The Right

The boundedness of the motions of the dynamical system described by a differential inclusion with control vector is studied. It is assumed that the right-hand side of the differential inclusion is upper semicontinuous. Using positionally weakly invariant sets, sufficient conditions for boundedness of the motions of a dynamical system are given. These conditions have infinitesimal form and are expressed by the Hamiltonian of the dynamical system.

scholarly journals Stability Analysis of a Model of Interaction Between the Immune System and Cancer Cells in Chronic Myelogenous Leukemia

2017 ◽  
Vol 80 (5) ◽  
pp. 1084-1110 ◽  
Author(s):  
Apollos Besse ◽  
Geoffrey D. Clapp ◽  
Samuel Bernard ◽  
Franck E. Nicolini ◽  
Doron Levy ◽  
...  
Keyword(s):  
Immune System ◽  
Stability Analysis ◽  
Cancer Cells ◽  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia

New Agents in Chronic Myelogenous Leukemia

2003 ◽  
Vol 1 (4) ◽  
pp. 501-512
Author(s):  
Jorge Cortes ◽  
Francis Giles
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Mechanisms Of Action ◽  
Myelogenous Leukemia ◽  
New Agents ◽  
Complete Eradication ◽  
Intracellular Pathways

Multiple new agents are currently being developed in chronic myelogenous leukemia (CML). Most of these agents are now being investigated in patients who have developed resistance to imatinib. Their mechanisms of action are diverse and many may be synergistic with imatinib. These agents will be used soon in different combinations, most likely including imatinib, with the hope of obtaining a complete blockade of the intracellular pathways that are triggered by Bcr-Abl. If this is successful, complete eradication of disease may become a reality for the majority of patients with CML.

scholarly journals 9-(2-Phosphonyl-methoxyethyl)-adenine promotes erythrocytic differentiation and disrupts cell replication in chronic myelogenous leukemia K562 cells

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Brittany Wiseman
Keyword(s):  
Cancer Treatment ◽  
Cancer Cells ◽  
Chronic Myelogenous Leukemia ◽  
Cellular Differentiation ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
Cell Replication ◽  
Protein Subunit ◽  
Hematopoietic Stem ◽  
Gamma Globin

Disruption during cellular differentiation can cause hematopoietic stem cells to proliferate uncontrollably, resulting in the development of cancer. Differentiation therapies are being investigated as a type of cancer treatment which involve inducing agents that promote the differentiation of cancer cells into those with similar properties to normal blood cells. These cells can then undergo apoptosis at an accelerated and controlled rate compared to cancer cells, making this a potential therapeutic technique. In this study, the ability of human chronic myelogenous leukemia K562 cells to undergo cellular differentiation in response to the inducing agent 9-(2-Phosphonyl-methoxy ethyl)-adenine (PMEA) is investigated. PMEA has previously been shown to disrupt cell replication, and promote erythrocytic differentiation in K562 cells. In order to further test the effectiveness of this inducer, cell proliferation was measured with a cell growth curve, hemoglobin presence was measured with benzidine staining, and gamma-globin expression (a protein subunit of fetal hemoglobin) was measured in both induced and uninduced K562 cell cultures via RT-qPCR and western blotting. The results indicate that PMEA slows cell replication, and promotes hemoglobin (and subsequently gamma-globin) expression in treated cells. In summary, the findings support the conclusion that PMEA is able to promote erythrocytic differentiation in K562 cells, and provides information that supports differentiation therapies as a method for cancer treatment.

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