Je možné pomocí časné molekulární odpovědi a její kinetiky předpovědět další osud pacientů s chronickou myeloidní leukemií?

Title in English Is it possible to predict the fate of chronic myeloid leukaemia patients by assessing early molecular response and its kinetics?
Authors

HORŇÁK Tomáš MAYER Jiří ŽÁČKOVÁ Daniela

Year of publication 2021
Type Article in Periodical
Magazine / Source Transfuze a hematologie dnes
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.prolekare.cz/casopisy/transfuze-hematologie-dnes/2021-4-14/je-mozne-pomoci-casne-molekularni-odpovedi-a-jeji-kinetiky-predpovedet-dalsi-osud-pacientu-s-chronickou-myeloidni-leukemii-129013
Doi http://dx.doi.org/10.48095/cctahd2021283
Keywords chronic myeloid leukaemia; Mathematical models; treatment-free remission; molecular monitoring; early molecular response; halving time
Description Management and therapy of patients with chronic myeloid leukaemia (CML) has changed significantly over the past twenty years. Quantitative RT-PCR detection of the BCR-ABL1 transcript level has become the gold standard for evaluating response to tyrosine kinase inhibitors (TKI) treatment. Demand for standardization of methodologies resulted in the international harmonisation of test result interpretation by expressing these on an international scale and assigning conversion factors to individual laboratories based on their comparison with reference sites. Early molecular response to treatment significantly influences the disease course and selects patients with good prognosis. Some of the patients who do not experience an early response still have good prospects in terms of disease course, as it is possible to take into consideration the kinetics of transcript level early decrease in order to exclude the high-risk group. The “halving time” concept indicates a high success rate for predicting disease sensitivity to the treatment given. In the era of long-term TKI therapy, attempts at a treatment-free remission (TFR) are being cited more frequently. This strategy involves the possibility of interrupting treatment without disease recurrence, decreasing adverse effects and the economic burden. Even today, identification of patients who are able to achieve this goal is hard and stable TFR is achieved only in a minority of patients. Treatment strategy may thus involve opting for a maximum possible reduction of TKI dose while still preserving treatment response. CML is not only a paradigm because of targeted treatment and its success rate but also because of its amenability for mathematical modelling of an oncological disease, given the simplicity of tumour load examination from peripheral blood and its real-time observation. This allows for easily acquired accurate data to be entered into the models. Using such models, we can simulate the origin of CML from the leukemic stem cell, TKI influence on these cells, various dosage regimens, attempts at TFR or the immune system response to presence of the disease. The following paper provides an overview of the principles of molecular measurement of treatment response, the consequences of early response and its kinetics on patient prognosis, and mathematical models of CML in the organism.

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