The tyrosine kinase inhibitor (TKI) imatinib in rare cases can cause acute toxic hepatitis, hepatic failure, and death. Currently, the choice of further chronic myeloid leukemia (CML) therapy in patients after acute hepatotoxicity is still a difficult question, which requires a complex individual approach based on the clinical guidelines of adverse event management. Data about the further follow-up strategy approach in patients with CML after acute toxic imatinib-induced liver injury are of concern, and at times controversial. In addition, one of the questions is about the necessity and safety of the imatinib therapy resumption after acute hepatotoxicity. In some publications, imatinib resumption without the recurrence of hepatotoxicity has been discussed; in others, imatinib resumption with the recurrence of imatinib hepatotoxicity has been mentioned. There are a few publications about the experience of administration of the second-line TKIs after acute imatinib hepatotoxicity. There are no clear data on which factors the physician’s decision should be based on in patients with CML after acute toxic imatinib-induced liver injury. Imatinib should be restarted or withdrawn, when and for whom second-line therapy should be started. The physician’s decision is usually based on the published data of similar cases, personal experience, and the severity of hepatotoxicity. We have discussed the clinical guidelines devoted to the peculiarities of the patient’s management after acute toxic imatinib-induced hepatitis and main strategy approaches. A complex score-based decision algorithm for choosing the further strategy approach after acute toxic imatinib-induced hepatitis in patients with CML has been presented. The following parameters should be assessed: the grade of hepatotoxicity reaction, the presence of liver transplantation or imatinib-induced liver cirrhosis and its possible pathogenetic mechanism, the presence of early molecular response (EMR) to imatinib therapy defined as three-month BCR-ABL1 ≤10% according to the international scale ( BCR-ABL1 IS ) or/and six-month BCR-ABL1 IS <1%; and the presence of the offender concomitant drug that probably caused the drug interaction with imatinib and the presence of viral hepatitis reactivation identified by polymerase chain reaction (PCR).

The introduction of imatinib has substantially changed the approaches to the therapy of chronic myeloid leukemia. However, this drug can cause hepatic failure and death in rare cases. This report describes a clinical case of acute, toxic imatinib-induced hepatitis in a 56-year-old woman with chronic myeloid leukemia and concomitant sulfa allergy and rheumatoid arthritis. The patient developed acute imatinib-induced hepatitis after three months of treatment with imatinib and three days after increasing the imatinib dosage from 400 mg per day to 600 mg per day, resolving within three months after imatinib discontinuation and prednisolone administration. This confirms the necessity of great caution during imatinib therapy and the monitoring of liver tests. Approximately 25 reports about clinical cases of imatinib-induced hepatitis have been published up to the present.

Significant progress has been achieved in treating patients with onco-hematological diseases, including chronic myeloid leukemia (CML). This is primarily associated with the development of targeted therapy involving tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, bosutinib, dasatinib, and ponatinib. Along with the increased survival of patients with CML, special attention has recently been paid to cardiovascular complications in CML patients due to the prevalence of cardiovascular diseases in the general population and the toxicity profile of targeted drugs. This article presents the strategy for reducing cardiovascular risk in CML patients treated with TKIs. We discuss the components of cardiovascular risk in CML patients and the findings of current studies. Current data confirm the increased cardiovascular risk in the CML population compared to the general population, which necessitates the widespread introduction of cardiovascular prevention strategies in CML patients. The pharmacokinetics and pharmacodynamics of TKIs on the cardiovascular system are discussed. We propose two main approaches in the strategy of cardiovascular risk prevention in patients with CML, namely, before the start of TKI administration and during TKI treatment. This article presents the diagnostic assessment before prescribing TKIs, as well as while monitoring TKI therapy, and discusses the features of the choice of TKIs depending on patients' general and cardiovascular comorbidity. Emphasis is placed on the risk stratification in patients with CML following general population algorithms, lifestyle modifications, and statin therapy for achieving the target levels of cardiovascular indicators. We also discuss unsolved questions in the current clinical guidelines and ways to further develop a cardiovascular risk-reducing strategy for CML patients.

Currently the most important direction in the sphere of higher medical education is the necessity to significantly strengthen the practical aspect of training future physicians, as well as quality postgraduate training while maintaining an appropriate level of theoretical knowledge. The classical system of higher clinical medical education is not able to fully solve the problem of practical training of physicians. The article describes practical-oriented case-method for study of internal medicine with the electronic database of clinical cases, trainers, thematic web quests in the educational process of clinical departments of higher medical institutions and discussed the necessary to establish a university database of clinical cases that can significantly improve the quality of education as undergraduate, as well as postgraduate stages. The article presents the main components of a case study method based on own experience of information web technologies implementation to the educational process: presentations of clinical cases - detailed presentation of a clinical case with visualization results of the examination, review of clinical guidelines important for presented in case pathology, discussing the peculiarities of the clinical case, treatment outcomes, discussion, outstanding issues, prospects of research, etc.; Video lectures of clinical cases with presentations; Practical training simulators - a combination of theoretical material on a specific topic with a large number of clinical situational tasks for it’s mastering; the simulators of clinical cases - a combination of a specific clinical case with logically related test tasks on the topic of the concrete clinical situation; medical educational web-quests are a combination of several topics in the medical discipline due one problem task with the elements of the detective-style information game, with the construction of a branching scenario and a combination of theoretical material on several topics, with the improvement of practical skills and test simulators. The article discussed the advantages and ethical aspects of implementing an electronic database of clinical cases for all participants in the educational process.

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