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Information × Registration Number 0219U003595, 0116U003574 , R & D reports Title The role of BCR/ABL gene mutations, chromosome, molecular genetic abnormalities and immunogenetic parameters in formation of approaches to optimization of target therapy in patients with chronic myeloid leukemia in the remote period after the Chornobyl power plant accident. popup.stage_title Head Dyagil I.S., Minchenko J.M., Registration Date 29-01-2019 Organization State institution "National research centеr for radiation medicine of the National academy of medical sciences of Ukraine " popup.description2 The object of the study - patients with chronic myeloid leukemia receiving treatment with tyrosine kinase inhibitors (TKI). The purpose of the research was to optimize and individualize target therapy of chronic myeloid leukemia, taking into account the mutation status, the level of BCR /ABL gene expression, chromosomal abnormalities and immunogenic indexes. Methods of research - hematological, cytogenetic, molecular genetic, immunogenetic, cultural and statistical. Research results. 58 patients with CML were examined, who achieved a deep molecular response to tyrosine kinase inhibitors, 70 patients with CML, resistant to TKI and 25 patients with radiation history of CML. Patients with CML with a radiation history did not reveal the specific clinical course of the disease. Among the specific radiation-associated genetic disorders, the mutation frequency was about 71% due to mutations of epigenetic modifiers, transcription factors. According to the study results, a complex of prognostic criteria associated with the formation of a deep molecular response to the treatment of tyrosine kinase inhibitors in CML patients was identified to create a group of patients for follow-up without TKI therapy, namely: chronic phase of CML, no splenomegaly, leukocytosis below 100 G/l, absence of additional chromosomal abnormalities, e14a2 BCR/ABL1 transcript; increasing of IFN-gamma and IL-2 level, achieving a complete cytogenetic response and level of BCR /ABL1 expression less 1% at 3 months of imatinib therapy and the level of BCR/ABL1 expression less 0.1% at 6 months of imatinib therapy. A complex of prognostic criteria for early evaluation of the TKI therapy effectiveness in CML patients was made for the individualization of target therapy: during diagnosis - the intermediate and high prognostic Sokal index, the presence of additional chromosomal aberrations in Ph-positive cells, e13a2 BCR /ABL1 transcript type, DRB1*11 carrier , high levels of IL-8 (more 41.3 ± 1.32) pg / ml and low IL-2 (less 4.3 ± 0.65) and IFN-gamma levels were unfavorable prognostic factors; at 3 months of therapy - the level of BCR/ABL expression more 8.55% and the preservation of high proliferative activity of hematopoietic cells were determined as the prognostic features of failure to reach the optimal response to TKI therapy during the next year and necessity of treatment correction; the appearance of mutations in the BCR/ABL1 kinase domain at any stage of therapy requires the change of the inhibitor, taking into account the sensitivity of the mutant clone. For optimization and individualization of TKI therapy were recommended: early diagnosis of CML; reducing the timing of treatment with chemotherapeutic drugs until the appointment of the TKI; obligatory monitoring of the therapy response within certain time limits; in irradiated patients with CML - the appointment of combined therapy of TKI with interferons; the appointment of imatinib in a dose of 800 mg/day, or nilotinib in a dose of 800 mg/day in patients with primary resistance risk factors during diagnosis. Product Description popup.authors Балан Валентина Володимирівна Дмитренко Ірина Віталіївна Дмитренко Олена Олександрівна Мартіна Зоя Володимирівна Федоренко Віра Григорівна Шляхтиченко Тетяна Юрівна Шолойко Валентина Василівна popup.nrat_date 2020-04-02 Close