Generation of well-defined organic–inorganic hybrid materials with controllable size and morphology is challenging and an active area of modern research in view of their unique properties and thus multifunctional applications.
The introduction of BCR-ABL tyrosine kinase inhibitors to the treatment of chronic myeloid leukemia (CML) has significantly changed the long term therapy results.After an initial 12 months of therapy with tyrosine kinase inhibitor (TKI), a 3-log reduction of the BCR-ABL copies number on an international scale is possible in 22-46% of patients, depending on the TKI used. In TKI-responsive patients, long-term TKI treatment results are even better, with the BCR-ABL transcript level decreasing over time, even to the point of becoming undetectable. Therefore, an operational cure can be diagnosed in CML patients with an optimal response to 1 st -line TKI treatment, a therapy duration of longer than 5-8 years, and BCR-ABL transcript level below MR4.0-MR4.5 for a period of more than two years. The latter has been the basis of multiple concepts of permanent or periodic discontinuation of TKI treatment [treatment-free remission (TFR)]. Initial TKI discontinuation clinical trials resulted in satisfactory results, with a disease recurrence rate of c.40-60% after 2-3 years. The mechanism of disease recurrence was then studied, with detailed characterization of the CML stem cells (CML SCs) immunophenotype and the mechanisms of survival and self-renewal under TKI selective pressure. A better understanding of the biology of CML allowed the formulation of new therapy concepts of CML SCs eradication, and new criteria for successful TFR qualification.
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