Clinical and Diagnostic Significance of Endothelial Dysfunction and Myocardial Contractility in Patients With Acute Myeloid Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Change of global longitudinal strain of 15% or more relative to the initial values
研究概览
简要总结
Acute myeloid leukemia (AML) is a clonal neoplastic disease of the hematopoietic tissue associated with a mutation in the precursor cell of hematopoiesis, which results in a differentiation block and uncontrolled proliferation of immature myeloid cells.
Anthracycline antibiotics have been an integral part of the treatment of acute myeloid leukemia since the 1970s. However, the clinical usefulness of anthracyclines is limited primarily by the high incidence of cardiotoxicity. According to the European Society of Cardiology guidelines for cardio-oncology, cardiovascular toxicity is defined as any impairment of cardiac function associated with anticancer treatment, as the term encompasses both a wide range of possible clinical manifestations and an etiological relationship with various treatments, including chemotherapy, radiation therapy, immunotherapy and treatment with targeted drugs. Cardiovascular toxicity can be acute, subacute or delayed, manifesting many years after chemotherapy or radiation therapy, involving a number of cardiac structures, which can lead to the development of heart failure, coronary heart disease, valvular heart disease, arrhythmias, including cardiac conduction disorders and diseases of the pericardium.
Anthracycline-induced cardiotoxicity is the negative effect of anthracyclines on normal cardiac activity due to their toxic effects on the heart muscle and the cardiac conduction system. Anthracycline-induced cardiotoxicity manifests as asymptomatic left ventricular dysfunction in 57% of treated patients and restrictive or dilated cardiomyopathy leading to congestive heart failure (CHF) in 16% to 20% of patients. Anthracycline-induced congestive heart failure is often resistant to therapy and has a mortality rate of up to 79%. Thus, there is a need for early detection of cardiovascular dysfunction associated with chemotherapy treatment of acute myeloid leukemia in order to timely prescribe drug therapy.
Purpose of the study To optimize the early detection of endothelial dysfunction and left ventricular myocardial contractility in patients with acute myeloid leukemia during chemotherapy treatment based on a comprehensive assessment of instrumental and laboratory research parameters.
Expected results Based on a comprehensive analysis using laser Doppler flowmetry, stress echocardiography with the determination of global longitudinal strain of the myocardium, biochemical markers of endothelial damage and cardiac biomarkers, a correlation between violations of the contractility of the left ventricular myocardium and violations of the vasoregulatory function of the vascular endothelium will be revealed, which will allow developing an algorithm for early detection of cardiomyopathy and vascular complications in patients with acute myeloid leukemia during chemotherapy treatment.
详细描述
Acute myeloid leukemia (AML) is a clonal neoplastic disease of the hematopoietic tissue associated with a mutation in the precursor cell of hematopoiesis, which results in a differentiation block and uncontrolled proliferation of immature myeloid cells.
It is believed that AML affects an average of 3-5 people per 100,000 people per year. At the same time, the incidence increases sharply at the age of over 60 years and amounts to 12-13 cases per 100 thousand of the population in people over the age of 80 years. The median age of this disease is 65 years. With a population of 140 million inhabitants in Russia, the estimated incidence rate (according to European and American researchers) should be about 5 thousand cases.
Anthracycline antibiotics have been an integral part of the treatment of acute myeloid leukemia since the 1970s. Anthracycline is usually given for 3 days (eg, daunorubicin 45-90 mg/m 2 daily, idarubicin 12 mg/m 2 daily) in combination with cytarabine (100-200 mg/m 2 daily) continuously for 7 days ) ("7+3" mode). Anthracyclines block the synthesis of DNA and RNA by inhibiting the enzyme topoisomerase IIβ and mitochondrial topoisomerase I. The subsequent disruption of DNA replication and transcription prevents the proliferation of rapidly dividing cells. In addition, anthracyclines damage DNA, proteins, and cell membranes by creating free oxygen radicals.
The clinical usefulness of anthracyclines is limited primarily by the high incidence of cardiotoxicity. According to the European Society of Cardiology guidelines for cardio- oncology, cardiovascular toxicity is defined as any impairment of cardiac function associated with anticancer treatment, as the term encompasses both a wide range of possible clinical manifestations and an etiological relationship with various treatments, including chemotherapy, radiation therapy, immunotherapy and treatment with targeted drugs. Cardiovascular toxicity can be acute, subacute or delayed, manifesting many years after chemotherapy or radiation therapy, involving a number of cardiac structures, which can lead to the development of heart failure, coronary heart disease, valvular heart disease, arrhythmias, including cardiac conduction disorders, and diseases of the pericardium.
Anthracycline-induced cardiotoxicity is the negative effect of anthracyclines on normal cardiac activity due to their toxic effects on the heart muscle and the cardiac conduction system. It is believed to be mediated in part by reactive oxygen species generated by anthracycline treatment, which leads to lipid peroxidation and DNA damage in cardiomyocytes. Other putative causes of anthracycline-induced cardiotoxicity include accumulation of cardiotoxic anthracycline metabolites in the heart, disruption of calcium homeostasis, mitochondrial damage, and induction of apoptosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients with acute myeloid leukemia receiving anthracycline-containing polychemotherapy regimens aged 18 to 65 years, without clinical signs of heart failure, with an LV ejection fraction of more than 50% before starting chemotherapy;
- •availability of informed consent of the patient to participate in the study.
排除标准
- •acute violation of cerebral circulation in history;
- •a history of myocardial infarction;
- •the presence of diabetes mellitus type I and II;
- •the presence of chronic kidney disease C1-C5 stages;
- •the presence of stable angina III-IV functional classes;
- •the presence of unstable angina pectoris;
- •the presence of atrial fibrillation and flutter;
- •the presence of arterial hypertension of 2-3 degrees;
- •the presence of other oncological diseases;
- •inflammatory diseases in the acute stage;
- •diseases of the thyroid gland;
- •therapy with any monoclonal antibodies in history;
- •a positive test for the presence of HIV and hepatitis B and C;
- •alcoholism, drug addiction;
- •the presence of neuroleukemia, extramedullary foci of leukemia;
- •refusal of the patient to be examined.
- •the emergence of life-threatening situations during the study;
- •development in patients of diseases related to the non-inclusion criteria;
- •refusal of the patient to further examination.
结局指标
主要结局
Change of global longitudinal strain of 15% or more relative to the initial values
时间窗: Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.
Change of global longitudinal strain of the myocardium according to stress echocardiography by 15% or more relative to the values obtained before the start of chemotherapy treatment.
次要结局
- Change of the Coefficient of Variation of Microcirculation According to Laser Doppler Fluometry(Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.)
- Change of the index of microcirculation according to laser Doppler flowmetry(Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.)
- Change of the level of endothelin-1(Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.)
- Change of brain natriuretic peptide level(Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.)
- Change of the level of asymmetric dimethylarginine(Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.)
- Change of the level of highly sensitive T-troponin(Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.)