[Assessment of systemic inflammation activity, myocardial structure and functional features, their relationship in patients with multiple myeloma, receiving bortezomib therapy].

AIM: To study the dynamics of calculated indices [neutrophil-lymphocyte ratio (NLR); systemic inflammation index (SIV)] and biomarkers of systemic inflammation [interleukin-1ß (IL-1ß); high-sensitivity C-reactive protein (hsCRP)], parameters of the structure-and-function state of the myocardium and intracardiac hemodynamics, and their relationship in patients newly diagnosed with multiple myeloma (MM) at the onset of the disease and after 6 courses of chemotherapy (CT) containing the proteasome inhibitor bortezomib. MATERIAL AND METHODS: This prospective study included 30 patients aged 63.8±10.0 years diagnosed with MM; 17 (56.7 %) of them were men. The following tests were performed for all patients: measurement of IL-1ß and hsCRP, calculation of the inflammation indexes NLR and SIV, transthoracic echocardiography before and after 6 courses of bortezomib-containing CT. At the time of study completion, 9 patients dropped out due to reasons not related to cardiovascular complications of CT. RESULTS: The antitumor therapy was associated with increases of immune-inflammation indexes: NLR increased from 1.54 [1.02; 1.83] to 2.9 [1.9; 4.35] (p=0.009) and SIV increased from 402.95 [230.5; 534.0] to 1102.2 [453.1; 1307.9] (р=0.014). IL-1ß increased from 5.15 [4.05; 5.77] to 6.22 [5.66; 6.52] pg/ml remaining within the reference range (p=0.142) whereas hsCRP decreased from 1.02 [0.02; 2.71] to 0.02 [0.02; 0.82] IU/l (p=0.138). Statistically significant changes in parameters of heart remodeling and clinical picture of cardiovascular complications were not observed. A correlation analysis showed significant inverse correlations of hsCRP with left ventricular ejection fraction (LV EF) (r= -0.557; p=0.003), the number of plasma cells (PC) with LV EF (r= -0.443; p=0.023), and a direct correlation of the number of PC with hsCRP (r=0.433; p=0.022). CONCLUSION: During the study, the accepted criteria for cardiotoxicity of bortezomib-containing chemotherapy in patients with MM, were not met. The identified correlations between the level of markers for acute inflammation, indexes of intracardiac hemodynamics, and the immediate MM substrate may indicate the role of chronic low-intensity inflammation in the pathogenesis of myocardial remodeling in patients with MM. This necessitates further studies on larger samples of patients to assess the prognostic significance.

[Difficulties in diagnosing intestinal T-cell lymphoma. Case report].

The article describes a rare diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), due to its veiled by a number of so-called "masks" of enteropathies. A detailed analysis of all clinical, morphological and immunohistochemical data made it possible to establish the correct diagnosis. The revealed pathology is extremely rare in practice, even among specialists in hematology. The article demonstrates the main stages of both a complex diagnosis and an attempt at therapy for this aggressive form of intestinal lymphoma.

Relationship Between Markers of the Acute Phase of Inflammation, Parameters of Blood Lipid Composition and Intracardiac Hemodynamics During Chemotherapy in Patients With Multiple Myeloma.

Aim      To evaluate in a pilot study time-related changes in the clinical state, indexes of the acute phase of inflammation, parameters of blood lipid profile, intracardiac hemodynamics, and disorders of cardiac rhythm/conduction in patients who are not candidates for autologous hemopoietic stem cell transplantation, during three bortezomib-containing chemotherapy courses (VCD) followed by a correlation analysis.Material and methods  This pilot study included 20 patients diagnosed with myeloma, who were not candidates for autologous hemopoietic stem cell transplantation and who had undergone three courses of VCD chemotherapy (bortezomib, cyclophosphamide and dexamethasone). In addition to mandatory examinations, measurement of blood lipid profile, transthoracic echocardiography (EchoCG), and 24-h Holter electrocardiogram (ECG) monitoring were performed for all participants before and after a specific therapy.Results Following three bortezomib-containing courses of chemotherapy, patients of the study group had significant increases in the neutrophil-lymphocyte ratio (NLR) (1.6±0.2 and 2.5±0.4; р=0.05), cholesterol concentration (4.8±1.1 and 5.6±1.1 mmol/l, р=0.05), and low-density lipoprotein concentration (2.8±0.4 and 3.5±0.8 mmol/l, р=0.02). In comparing the changes in parameters of intracardiac hemodynamics, criteria for genuine cardiotoxicity were not met, however, a tendency to emergence/progression of myocardial diastolic dysfunction was noted. No clinically significant disorders of cardiac rhythm/conduction were observed. The correlation analysis performed prior to the start of chemotherapy, showed significant strong, direct correlations between the C-protein concentration and left atrial (LA) volume (r=0.793; p=0.006), right atrial (RA) volume (r=0.857; p=0.002), left ventricular (LV) end-diastolic dimension (EDD) (r=0.589; p=0.043), and LV end-diastolic volume (EDV) (r=0.726; p=0.017). Following the specific treatment, significant, medium-power and strong correlations were found between NLR and EDV (r= -0.673; p=0.033), NLR and end systolic volume (ESV) (r= -0.710; p=0.021), respectively. Significant direct correlations were found between the bortezomib dose per one injection and the serum concentration of triglycerides following the treatment (r=0.78; p=0.05); a single bortezomib dose and parameters of intracardiac hemodynamics: LA (r=0.71; p=0.026), RA (r=0.74; p=0.014), EDD (r=0.837; p=0.003), EDV (r=0.749; p=0.013), ESV (r=0.553; p=0.049).Conclusion      For the first time, a comprehensive evaluation was performed in patients with multiple myeloma, including the dynamics of blood lipid profile, intracardiac hemodynamics and disorders of cardiac rhythm/conduction during bortezomib-containing antitumor therapy, with an analysis of correlation with levels of acute inflammation phase markers. Although in the observation window for genuine cardiotoxicity, clinically significant cardiovascular complications were not detected, the found correlations may evidence a potential role of systemic inflammation activity in myocardial remodeling in the studied patient cohort.

[Assessment of the Dynamics of Oxidative Stress Indicators and Early Markers of Myocardial Damage and Dysfunction in Patients with Aggressive Lymphoproliferative Diseases During of Anticancer Therapy].

Aim      To evaluate the dynamics of indexes of oxidative stress and markers of myocardial injury and dysfunction in patients with aggressive type lymphomas during the antitumor therapy.Material and methods  This study included 75 patients with lymphoproliferative diseases of aggressive type. The main group consisted of 53 patients who received one course of antitumor therapy during the study. The comparison group consisted of 22 patients who have not received any specific treatment so far. Troponin I (TnI), high-sensitivity troponin (hsTnI), heart-type fatty acid binding protein (Н-FAВР), N-terminal pro-brain natriuretic peptide (NT-prоBNP), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in patients of both groups at baseline, and in the main group, they were measured at 4 hours after administration of antitumor agents and on completion of the course. Functional status of the cardiovascular system was evaluated by electrocardiography in all patients at baseline and after the course of antitumor treatment and by echocardiography.Results The chemotherapy was associated with increased levels of NT-prоBNP, SOD, and MPO (30.670±15.367 vs. 52.309±25.718 pmo l/l; 1.61±0.135 vs. 1.74±0.193 U/ml; and 507.54±91.51 vs. 742.3±49.01 ng/ml, respectively). The study results indicated activation of oxidative stress on the background of the administered antitumor therapy, progressive myocardial dysfunction, and increased frequency of arrhythmic episodes.Conclusion      The study results allowed identifying NT-prоBNP, MPO, and SOD as important indexes for determining a patient group at high risk of cardiotoxicity during the antitumor treatment.

[Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow].

Aim      To study changes in markers for myocardial direct injury and dysfunction and endothelial dysfunction (ED) indexes in patients with indolent lymphoma during the antitumor treatment.Material and methods  Current antitumor therapy for lymphoma is often associated with cardio- and vasculotoxicity, studying of which is a relevant scientific direction. Markers for myocardial direct injury and dysfunction and ED indexes were studied in patients with indolent lymphomas receiving polychemotherapy (PCT). The study included 77 patients with newly diagnosed indolent type lymphoma. The main group (n=52): mean age, 63.4±2.8 years, 15 (28.8 %) men who had received one course of PCT. The comparison group (n=25): mean age, 61.8±3.7 years, 8 (32 %) men who had not received PCT. Troponin I (TnI), high-sensitivity troponin I (hs-сTnI), heart-type fatty acid binding protein (h-FAВР), and N-terminal pro-B-type natriuretic peptide (NT-prоBNP) were measured in patients of both groups. ED was evaluated by measuring the level of vascular cell adhesion molecule (VCAM) and by assessing the structure and function condition of small blood vessels using photoplethysmography. In both groups, the study parameters were determined at the start of the study (T1) and following the PCT course in the main group; if the PCT schedule included anthracycline antibiotics, the second point (T2) was assessed at 6 h following the drug administration.Results In both groups, the level of NT-proBNP was increased. This increase was significantly more pronounced in the comparison group (49.896±23.228 vs 20.877±8.534 pmol/l, respectively, p=0.011) whereas a tendency to its increase was observed after the PCT course. Before the start of the treatment, laboratory and instrumental signs of ED were noticed: the level of VCAM was 4951±1297 and 3225±757 ng/ml in the comparison group and the main group, respectively (р=0.246); reflection index was <1.8 in 23 (44.2%) patients of the main group and in 16 (64%) patients of the comparison group (р=0.098). During the PTC course, the endothelial function significantly improved; the level of VCAM decreased by 748 ng/ml (p=0.016), which was associated with significant decreases in erythrocyte sedimentation rate by 2.71 mm/h (р=0.027) and lactate dehydrogenase level by 62.38 U/l (р=0.026). Statistically significant decreases in other inflammatory markers (alpha-2-globulin, fibrinogen, C-reactive protein, neutrophil count) were not observed.Conclusion      The level of NT-proBNP showed the highest sensitivity in assessing the cardiotoxic effect of PCT. The dynamics of VCAM level suggested a possible role of the disease itself in the development of ED in this patient group.

[Assessment of the Role of Oxidative Stress Indicators and Early Markers of Myocardial Injury and Disfunction in Patients with Lymphoproliferative Diseases].

PURPOSE: to study dynamics of indicators of oxidative stress and their role in development of cardiotoxicity in patients with lympho-proliferative diseases at the background of polychemotherapy. MATERIALS AND METHODS: We included into this study 30 patients with newly detected Non-Hodgkin lymphomas. The control group comprised 15 healthy volunteers. For registration of dynamics of formation of oxygen active forms (OAF), we used highly sensitive chemiluminescence assay. The state of initial stage of lipoperoxidation OAF and radicals of organic compounds) was assessed by dynamics of the leukocyte chemiluminescence. The state of final stage of lipoperoxidation (formation of nonmetabolizing lipid hydroperoxides and other compounds) was assessed by the level of malonic dialdehyde. We also determined indicator of leukocyte chemiluminescence intensity (both basal and zymosan-stimulated). For assessment of the cardiovascular system functional state before and after chemotherapy we used electrocardiography (ECG), echocardiography (EchoCG) and 24-hour ECG monitoring. RESULTS: The data obtained were indicative of increased generation of free radicals by leukocytes during polychemotherapy. After chemotherapy course we detected various types of cardiotoxicity. We noted substantial elevation of frequency of supraventricular and ventricular extrasystoles. There was direct correlation between rate of appearance of supraventricular extrasystoles and level of chemiluminescence of leukocytes (r=0.7; p=0.03). According to data of EchoCG although the left ventricular ejection fraction remained within the normal range during chemotherapy, there was a persistent tendency to its decrease (р<0.001). CONCLUSION: In this study we for the first time in patients with Non-Hodgkin lymphomas detected an elevation of level of free radical reactions and lipid peroxidation with simultaneous lowering of antiperoxidative activity of blood plasma and their relation to development of cardiotoxic effects. The results obtained indicate to necessity of search for novel early markers of oxidative stress activation, myocardial injury and disfunction able to help to substantially decrease risk of development of cardiovascular complications during and after chemotherapy.

[A case of rare inhibitory coagulopathy - acquired hemophilia A].

Inhibitory coagulopathy is a rare variant of hemorrhagic syndrome. Acquired hemophilia A is caused by the formation of inhibitors (antibodies) to Factor VIII of the blood coagulation system leading to impaired activation of the key stage of blood clotting (factor X) and development of hemorrhagic syndrome of different severity. Acquired hemophilia A is a rare disease with an incidence of 1.38-1.48 per 1 million population per year. We report a case off severe idiopathic acquired hemophilia A in a 53 year-old woman manifest as skin hemorrhages, subcutaneous and intramuscular hematomas. Hemostatic therapy described in the article resulted in the elimination of hemorrhagic syndrome and complete remission. This case represents a rare disease the knowledge of which can be useful for preventing the development of debilitating complications, and sometimes saving the patient's life.

[LISHUTA EXTRANODAL INVOLVEMENT OF THE HEART IN LYMPHOMAS: A CLINICAL CASE OF LARGE B-CELL LYMPHOMA AND LITERATURE REVIEW].

The authors report a case of rare cardiac involvement in lymphoma, one of the manifestations of which was rhythm and conduction disorders with their resolution after chemotherapy. Also presented are clinical manifestations of heart lesions in lymphoma and modern methods of their diagnostics and treatment.