Background. Recently, studies have been conducted all over the world to study the role of immune checkpoints in the pathogenesis of chronic lymphocytic leukemia (CLL) and the possibility of their use as prognostic markers. Of greatest interest are PD-1 (programmed cell death-1) and LAG-3 protein (lymphocyte-activation gene 3). Aim. To study the features of PD-1 (CD279) and LAG-3 (CD223) expression on blood B-cells of CLL patients and the possibility of their use as early markers for predicting the hematological response to therapy. Materials and methods. The blood of 30 patients with CLL in stage C according to Binet and 20 healthy individuals was studied by 10-color flow cytometry. Results. In patients with CLL, there were significant differences in the initial lymphocytes level, PD-1 and LAG-3 expression on B-lymphocytes, both with persons in the control group and among themselves with different hematological responses to therapy with rituximab according to the results of minimal residual disease monitoring. Conclusion. PD-1 and LAG-3 can be used as early markers for predicting the response of CLL patients to therapy. The combined use of initial lymphocytes level and PD-1 and LAG-3 expression on CD19+ blood cells has a greater prognostic value. New data obtained from the study of immune checkpoints PD-1 and LAG-3 may be useful in the development of targeted therapeutic agents.

Purpose : to study the level of LAG-3 expression on B-lymphocytes and the feasibility of using it as a marker for predicting response to therapy in patients with chronic lymphocytic leukemia (CLL). Material and Methods . The study included 40 patients with newly diagnosed CLL. All patients were divided into two groups: group I: patients with Binet stage A, who did not receive therapy and group II: patients with Binet stage C, who received immunochemotherapy in RB and FCR regimes. According to the treatment regimen and hematological response to therapy, 4 subgroups were distinguished: IIA-RB, IIA-FCR, IIB-RB, and IIB-FCR. The control group consisted of 20 people matched in age and gender without cancer. The immunophenotype, level of B-lymphocytes, LAG-3 expression, and the minimal residual disease in group II after the 6th course of immunochemotherapy were initially determined in all groups by flow cytometry. The data were evaluated using Statistica 13.0. Results . Compared to the control group, the LAG-3 expression on B-lymphocytes was found in all groups of CLL patients before treatment. The expression level was higher in patients with Binet stage C than in patients with Binet stage. The data demonstrated differences in the level of LAG-3 expression in patients with different hematological responses to therapy. The initially higher level of LAG-3 expression on B-lymphocytes was observed in patients with Binet stage C CLL with an unfavorable response to therapy. A good hematological response was found can be achieved at the level of LAG-3 expression within 14.57 ± 0.66 % regardless of the therapy regimen, and unfavorable response to therapy at the level of 41.95 ± 1.62 %. Conclusion . The initial level of LAG-3 expression on B-lymphocytes in patients with CLL can be used as a marker for predicting and monitoring response to treatment, regardless of the immunochemotherapy regimen used.

ПЕРВИЧНАЯ МЕДИАСТИНАЛЬНАЯ В-КРУПНОКЛЕТОЧНАЯ ЛИМФОМА. ПОИСК ПРЕОДОЛЕНИЯ ИМЕЮЩЕЙСЯ РЕФРАКТЕРНОСТИКамаева И.А

A complex clinical case of acute myelomonocytic leukemia with extramedullary lesion of the testis is presented. patient yu., born in 1968, applied to the National Medical Research Centre for Oncology (Rostov-on-don) after an injury to the inguinal region. ultrasound was performed: in the right testicle in the middle third, a mass of 30 × 23 × 16 mm was revealed. A biopsy was performed: the morphological picture is characteristic of a typical seminoma. Orchofuniculectomy was performed on the right. Histopathological conclusion: the morphological picture is more characteristic of a typical seminoma, but does not allow excluding lymphoma. In order to differentiate between a germ cell tumor and a lymphoproliferative disease, an immunohistochemical study of the tumor tissue, a morphological and immunophenotypic study of the bone marrow were performed. According to the immunohistochemical data, the morphological picture and immunophenotype of tumor cells are characteristic of extranodal NK/T-cell lymphoma of the testis with Cd4 co-expression. However, according to the myelogram data, 20 % of morphologically heterogeneous blast cells were found: with round or bean-shaped nuclei, delicate mesh structure of chromatin, 1–2 nucleoli and a monocytoid form of nuclei with indistinct nucleoli. The cytoplasm of varying basophilia degrees, vacuolized, with delicate azurophilic granularity. The content of the monocytoid population was increased (19 %), represented mainly by promonocytes, which corresponds to acute myelomonocytic leukemia. According to flow cytometry, the immunophenotype of blast cells corresponds to acute myeloid leukemia with Cd56 co-expression. In connection with the new data obtained, the histological preparation was revised again with the expansion of the immunohistochemical study. Result: morphological picture and immunophenotype of tumor cells are characteristic of acute myelomonocytic leukemia with extramedullary lesions of the right testicular tissue. final diagnosis: acute myelomonocytic leukemia with extramedullary lesion of the right testicle, with Cd56 co-expression. The presented clinical case showed the need to use a wide range of diagnostic techniques to determine the nature of the disease. The results of morphological and cytometric studies of the bone marrow were decisive in establishing the diagnosis of M4 acute myeloid leukemia with extramedullary lesions of the right testicle in this patient.

Hodgkin's lymphoma is a malignant disease of the lymphatic system. Hodgkin's lymphoma was first described by Dr. Thomas Hodgkin in 1832 and later named “Hodgkin's disease” by Samuel Wilkes. Hodgkin's lymphoma accounts for about 24 % of all lymphomas. Hodgkin's lymphoma is classified as classical and nodular lymphoid-predominant (Nodular type of lymphoidpredominant Hodgkin's lymphoma). Classical Hodgkin's lymphoma includes the following histologic variants: nodular sclerosis variant (types I and II), mixed cell variant, classic lymphocyte-rich variant, and rare lymphoid depletion variant. Epidemiological and serological studies showed the involvement of the Epstein-Barr virus into Hodgkin's lymphoma etiology, since its genome was found in the study of the biopsy material samples from patients with Hodgkin's lymphoma. A relationship with the human immunodeficiency virus (HIV) was revealed as well, and patients infected with HIV have a significantly increased risk of developing Hodgkin's lymphoma compared to healthy people. An in-depth study of the Hodgkin's lymphoma pathophysiology revealed new therapeutic targets in the treatment of this disease. All these discoveries changed the understanding of the Hodgkin's lymphoma pathogenesis, and were important for the development of new methods of treatment. The history of therapy begins on the cusp of the 19th and 20th centuries. Over the past four decades, achievements in radiation therapy and combined chemotherapy have significantly improved overall survival of patients with Hodgkin's lymphoma. Currently, more than 80 % of patients under 60 years old with first diagnosed Hodgkin's lymphoma can be cured from this disease after first-line chemotherapy.

With a frequency of 2.2 cases per 100,000 population in Russia, Hodgkin's lymphoma (HL) is one of the most common malignant neoplasms in young people. In connection with the predominant spread of HL among young people, the issue of effective treatment of various forms of HL remains relevant. Currently, 70-90 % of patients with HL who have received standard chemotherapy or chemoradiotherapy have a long period of remission. However, 10 % of patients with progressive course, can`t achieve a response, and 30 % of patients subsequently recur. The standard approach of treating recurrent and/or refractory HL after initial treatment is “salvage therapy” followed by consolidation with high-dose chemotherapy and stem cell transplantation. Although there is a model for treating these patients, recent research has focused on improving the effectiveness and tolerability of rescue therapy. The use of anti- PD-1 drugs opens up new possibilities for the treatment of recurrent/refractory HL. The article describes the results of using checkpoint inhibitors for patients with a history of multi- course chemotherapy. Inhibitors of immune check points were supplemented in the 3rd and subsequent lines of ChT. A clinical case with immunotherapy supplementation in a patient with severe comorbidity is also presented.

ПОКАЗАТЕЛИ КОСТНОМОЗГОВОГО КРОВЕТВОРЕНИЯ У БОЛЬНЫХ С РАЗЛИЧНЫМ КЛИНИЧЕСКИМ ТЕЧЕНИЕМ ДИФФУЗНОЙ В-КРУПНОКЛЕТОЧНОЙ ЛИМФОМЫФранциянц Е.М. 1 , Гуськова Н

ВОЗМОЖНОСТЬ ПРОГНОЗИРОВАНИЯ РАЗВИТИЯ РЕЦИДИВА ПРИ ДИФФУЗНОЙ В-КРУПНОКЛЕТОЧНОЙ ЛИМФОМЕ С ИСПОЛЬЗОВАНИЕМ ПОКАЗАТЕЛЕЙ ОБЩЕГО АНАЛИЗА КРОВИФранциянц Е.М. 1 , Бандовкина В.А. 1 , Куштова Л

УДК 616-006.44ОЦЕНКА ВЗАИМОСВЯЗИ КОЛИЧЕСТВЕННОЙ ХАРАКТЕРИСТИКИ ОПУХОЛЕВЫХ В-ЛИМФОЦИТОВ И СТЕПЕНИ РАСПРОСТРАНЕННОСТИ ПОРАЖЕНИЯ ЛИМФАТИЧЕСКОЙ СИСТЕМЫ У БОЛЬНЫХ ХРОНИЧЕСКИМ ЛИМФОЦИТАРНЫМ ЛЕЙКОЗОМ Величко А.В. 1 , Камаева И

Primary bone lymphoma is a rare presentation of non-Hodgkin lymphoma. It accounts for a maximum of 1–2% of all non-Hodgkin lymphomas in adults. Primary bone lymphoma is diagnosed in focal lesions of one or more bones; soft tissue and regional lymph nodes may be involved too. The exclusion criteria are only bone marrow damage and involvement of distant lymph nodes. The first symptoms include intractable bone pain often accompanied by local edema, the formation of a tumor mass in the affected area; B symptoms occasionally join. Local lesions of long tubular bones in the diaphysis and metadiaphysis regions are more common (80%), while multifocal lesions are less frequent (20%). Diagnosis of lesions of the bone tissue in its primary and secondary involvement is based on the use of all available research methods (radiography; computed, magnetic resonance and positron emission tomography). Differential diagnosis requires an immunohistochemical study with determination of the expression of total leukocyte antigen, B-cell and T-cell markers, and clonality in one of immunoglobulin light chains κ or λ, bcl 2 and bcl 6, ALK, proliferative activity of Ki-67. Evaluation of the effectiveness of various treatments for primary bone lymphoma is complicated by a small number of observations and the absence of a uniform treatment strategy. CHOP-like chemotherapy cycles are often used as first-line therapy. Personalized therapy involves immunochemotherapy, radiation therapy and surgical treatment — endoprosthetics.

The prospects of using the selective plasma exchange in the treatment of first identified multiple myeloma (secretory) is substantiated (MM). Twenty-four patients (16 men and 8 women) were examined with stage II−III of the disease. Patients were divided into two groups: the main group (n = 13) with inclusion in therapy selective plasma exchange were included in the treatment and a control group (n = 11) — were treated according to standard protocol. The patients received specific treatment according to the VCD scheme. The concentrations of paraprotein, free light chains Ig (FLC), glomerular filtration rate (GFR), blood toxicity and the functional characteristics of albumin were studied. The studies were conducted before and after the completion of chemotherapy. Additionally, the concentration of paraprotein, FLC and MSM (molecules with average mass) in the blood serum were determined before and 30 min after the end of selective plasma exchange, as well as in the plasma filtrate. The results of the study showed that the inclusion of selective plasma exchange in the treatment ensured the excretion of more than 50 % of the paraprotein and FLC in the blood, a decrease in their concentration after the completion of the procedure: paraprotein 32 %, κ — FLC 43 %, λ — FLC 68 %. There was a greater regression of monoclonal protein levels and FLC production with a marked decrease in the indices of endogenous intoxication and an improvement in the functional properties of the albumin in the main group as compared with the control after completing the chemotherapy course. In the group of patients a more best to the therapy was obtained: a good response — in 69.2 % of the patients (in the control group — in 45.5 %); a negative response — in 30.8 % of cases against 54.5 % in the control group. The obtained results suggested that including selective plasma exchange in the specific complex therapy of patients with first identified multiple myeloma allows to reduce the volume of paraprotein, increase the degree and rate of reduction of LC, without affecting the toxicity of the therapy, which contributes to the strengthening of hematological and renal response to ongoing treatment.

Обоснована перспективность применения селективного плазмообмена при лечении первично выявленной секретирующей множественной миеломы. Обследовано 24 больных (16 мужчин и 8 женщин) II–III стадиями заболевания. Больные разделены на группы: основная группа (13 человек) — с включением селективного плазмообмена и контрольная (11 человек) — пролеченных по стандартному протоколу. Больные получали специфическое лечение по схеме VCD. Изучали уровень парапротеина, свободных легких цепей (СЛЦ) иммуноглобулинов, скорость клубочковой фильтрации (СКФ), маркеры почечного повреждения, токсичность крови, функциональные характеристики альбумина. Исследования проводили до начала лечения и после завершения курса химиотерапии. Дополнительно определяли концентрацию парапротеина, СЛЦ, содержание молекул средней массы (МСМ) в сыворотке крови перед проведением селективного плазмообмена и через 30 мин после завершения процедуры, а также в эксфузированном плазмофильтрате. Результаты исследования показали, что включение селективного плазмообмена обеспечивало выведение парапротеина — на 32 %, κСЛЦ — на 43 %, λСЛЦ — на 68 %. После завершения курса химиотерапии в основной группе отмечали более значительный регресс моноклонального белка, продукции СЛЦ, выраженное снижение показателей эндогенной интоксикации, улучшение функциональных свойств альбумина. В группе больных с применением селективного плазмообмена был получен более адекватный ответ на проводимую терапию: хороший ответ — у 69,2 % больных vs 45,5 % в контрольной группе; отрицательный — в 30,8 % случаев vs 54,5 % в группе контроля. Полученные результаты свидетельствуют о том, что включение селективного плазмообмена в комплекс специфической терапии больных первично выявленной секретирующей множественной миеломой позволяет уменьшить объем парапротеина, увеличить степень и скорость редукции СЛЦ, что способствует усилению гематологического и почечного ответа на проводимое лечение.

Background: Sepsis remains the leading cause of death in cancer patients. Biomarkers allow an objective and reliable possibility of rapid prediction of the septic process. The purpose of the study was to assess the prognostic significance of a rapid and accessible verification of the sepsis pathogens with biomarkers – procalcitonin and Platelia Candida Ag Plus Methods: The study included 440 patients with clinical manifestations of the inflammatory response in intensive care units, oncological and oncohematological departments. Levels of procalcitonin and Platelia Candida Ag Plus were determined by ELISA together with the blood sterility testing using the BacT/ALERT 3D analyzer. Results: The most common pathogens (78%) were bacteria (K. pneumoniae. E. coli, less often other members of the Enterobacteriaceae family, P. aeruginosa, A. baumannii, E. faecalis, E. Faecium, etc.); yeasts of Candida spp. – 22%; mixed pathogens – 7.5%, comprising 37.5% bacteria and 62.5% bacterial-fungal pathogens. Positive blood cultures were found in 106 (24.1%) patients. The results of a blood culture took on average 3 days. The use of two biomarkers allowed predicting a pathogen in the first hours after the blood collection. An increase in the levels of one biomarker in 137 (31.1%) patients with negative blood cultures indicated the presence of bacterial, fungal or bacterial-fungal infections. The blood culture examination together with determination of biomarkers improved verification of sepsis pathogens in 243 (55.2%) patients with clinical manifestations of sepsis and hastened preliminary results and empirical therapy. Conclusions: The study of the blood culture and determination of levels of the biomarkers allowed the prediction of pathogens in 243 (55.2%) patients with clinical manifestations of sepsis. 197 (44.8%) patients with negative blood cultures and normal levels of biomarkers required additional tests. Legal entity responsible for the study: Ministry of Health of the Russian Federation. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Drug therapy for symptomatic multiple myeloma is comparable for both sexes in its effectiveness and safety. A 3-year event-free survival is comparable in men and women; overall survival in men is lower than in women.