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Updated: Jul 24, 2025

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Chronic myeloid leukemia, tyrosine kinase inhibitors and cardiovascular system
1Department of Hematology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. umitmalkan@hotmail.com.
Objective:
Cardiovascular system health becomes important with the extended survival of chronic myeloid leukemia (CML) patients. Cardiotoxicities are related to the second- and third-generation tyrosine kinase inhibitors (TKIs). The most frequent and important cardiovascular events are myocardial infarction, stroke and peripheral arterial disease, QT prolongation, pleural effusions, and both systemic and pulmonary hypertension. The aim of this paper is to review the interactions between administrated TKIs and the cardiovascular system during the clinical course of CML. Elucidation of TKI effects on the cardiovascular system is vital since the current goal of CML therapy is a cure that leads to normal age and gender-similar survival with a normal quality of life.
Materials And Methods:
Up to August 2022, literature searches were performed via the internet search engines MEDLINE, EMBASE, GOOGLE SCHOLAR: (i) chronic myeloid leukemia; (ii) tyrosine kinase inhibitor; (iii) cardiovascular system. Only articles in English and research including humans were included in the search.
Results:
Tailored TKI treatment with individual patient characteristics must account for CML disease risk, patient age, patient comorbidities, patient compliance, TKI drug off-target risk profile, accelerated or blastic phase CML disease, pregnancy and allografting in CML. The treatment-free survival, improving quality of life, limiting adverse events of TKIs, and the optimal dose and administration duration of TKIs are still a matter of controversy. Special attention should be paid to the comorbidities of CML patients and clinical TKI effects on CVS since the aim of CML treatment is a cure that leads to normal age and gender-similar survival with a "normal" quality of life. CVS is an important morbidity and mortality cause for adult patients. The discontinuation of TKI treatment in CML and the treatment-free remission of CML patients are very important in order to reduce the risk for cardiovascular adverse effects of TKIs. The frail CML patients and especially the patients who have cardiac comorbidities, should be carefully evaluated for TKI treatment, and hematopoietic stem cell transplantation (HSCT) should be the last choice in these risky CML patients.
Conclusions:
The current CML treatment target is a cure that leads to normal age and gender-adjusted survival with a "normal" quality of life. Cardiovascular disorders are one of the major obstacles to reaching this target in CML patients. The treatment choices for CML patients must include a cardiovascular perspective.
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