Актуальность. Известно, что популяция неопухолевых плазматических клеток в костном мозге здоровых лиц весьма гетерогенна. Среди них может обнаруживаться небольшое количество плазмоцитов CD19–, CD56+, CD45–, отличающих их от основной массы нормальных клеток плазмоцитарного ряда отсутствием экспрессии CD19, CD45 и наличием экспрессии CD56. Именно это обстоятельство вносит определенные сложности в мониторинг минимальной остаточной болезни (МОБ) при множественной миеломе (ММ), поскольку необходимо проводить сопоставление аберрантных и нормальных плазматических клеток. По этой причине представляется чрезвычайно актуальным исследование ряда дополнительных диагностических маркеров: CD27, CD28, CD117 и CD81. Цель. Изучение роли дополнительных диагностических маркеров (CD27, CD28, CD117 и CD81) МОБ у больных ММ на различных этапах течения заболевания. Материалы и методы. В настоящее исследование включено 62 больных ММ в возрасте 31–76 лет (медиана 58 лет); женщин было 25, мужчин — 37. Анализу подвергнуты морфологические и иммунофенотипические особенности плазматических клеток костного мозга. Методом определения МОБ служила 8-цветная проточная цитометрия на проточном цитометре FACSCanto II (США) в соответствии с критериями EuroFlow. Результаты. Иммунофенотип плазматических клеток на этапе первичной диагностики ММ оценен у всех 62 больных с использованием двух 8-цветных панелей, рекомендованных консорциумом EuroFlow (2012). В соответствии с данными первичного иммунофенотипирования МОБ определялась на основании изучения как основных диагностических маркеров плазматических клеток (CD38, CD138, CD45, CD56, CD19), так и дополнительных (CD27, CD28, CD117 и CD81). Исследование проводилось в основном после индукционной терапии по достижении ремиссии. Установлено, что частота МОБ-положительных результатов при пороговом уровне аберрантных плазматических клеток более 0,01 % была следующей: по CD27 — 91 %, CD28 — 90,6 %, CD117 — 87 %, CD81 — 96,7 %. Соответственно МОБ-отрицательные случаи по маркеру CD27 составили 9 %, CD28 — 9,4 %, CD117 — 13 %, CD81 — 3,3 %. Заключение. Применение комплекса дополнительных маркеров CD27, CD28, CD117, CD81 позволяет более достоверно с учетом экспрессии основных антигенов CD38, CD138, CD45, CD56, CD19 установить МОБ-статус при ММ: отрицательный либо положительный.

Background. The population of non-tumor plasma cells in healthy subjects’ bone marrow is known to be fairly heterogeneous. Among them, there may be a small number of CD19-, CD56+, CD45- plasma cells which differ from the main bulk of the normal plasmacytic cells by the lack of CD19 and CD45 expression and the presence of CD56 expression. It is the fact which makes the monitoring of minimal residual disease (MRD) especially challenging in multiple myeloma (MM) since normal and aberrant plasma cells should be compared. For this reason, a study of such complementary diagnostic markers as CD27, CD28, CD117, and CD81 is extremely important. Aim. To analyze the role of complementary diagnostic markers (CD27, CD28, CD117, and CD81) of MRD in MM patients at different disease stages. Materials & Methods. The present study enrolled 62 MM patients aged 31-76 years (median 58 years); 25 women and 37 men. The analysis focused on morphological and immunophenotypic properties of bone marrow plasma cells. MRD was detected by 8-color flow cytometry with the use of FACSCanto II Flow Cytometer (USA) based on EuroFlow standards. Results. At the stage of primary diagnosis of MM, the imunophenotype of plasma cells was analyzed in all 62 patients using two 8-color panels recommended by the EuroFlow Consortium (2012). In accordance with primary immunophenotyping data, MRD was evaluated on the basis of not only the main diagnostic markers of plasma cells (CD38, CD138, CD45, CD56, and CD19), but also the complementary ones, such as CD27, CD28, CD117, and CD81. The study was basically conducted after induction therapy and upon remission. With cut-off > 0.01 % of aberrant plasma cells, the MRD incidence was the following: 91.0 % with CD27, 90.6 % with CD28, 87.0 % with CD117, and 96.7 % with CD81 markers. Respectively, no MRD was detected in 9.0 % with CD27, 9.4 % with CD28, 13.0 % with CD117, and 3.3 % with CD81 markers.

Relevance. Cutaneous T-cell lymphomas (CTCL) are not common diseases which are associated with a decrease in quality of life. Currently available systemic therapy rarely provides a stable and long-termed response. In Russia, current CTCL therapy is a big issue due to the limited access to modern targeted therapy, an absence of a National CTCL registry, and the difficulties in morphological diagnosis of these rare diseases. Since June 17, 2019, a new indication of brentuximab vedotin as a new treatment option for patients with CD30+ CTCL after at least one line of previous systemic therapy was registered. Brentuximab vedotin is a conjugate of a CD30 directed monoclonal antibody and an antitumor agent. Brentuximab vedotin is a CD30-directed monoclonal antibody conjugated to an antitumor agent. Aim. To identify the unresolved issues of current clinical practice and to adapt available approaches to the treatment and diagnosis of CD30 + CTCL given new therapeutic opportunities. Results. The available approaches to the systemic CTCL therapy in Russia routine clinical practice have been discussed, the unresolved issues of therapy and diagnosis have been identified, the routing of patients with CD30 + CTCL in Russia has been discussed, the importance of CD30 testing has been established, the profiles of patients with CTCL for treatment with brentuximab vedotin have been determined.

Background. Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is one of the primary extranodal tumors and originates from B-cells of thymic medulla. This disease is characterized by specific immunomorphologic and genetic features which distinguish it from other malignant lymphoproliferative disorders with similar parameters. Standard PMBCL treatment consists of immunochemotherapy and subsequent radiotherapy of residual mediastinal tumor. The advantages of one immunochemotherapy regimens over the other in controlled studies have not been shown. Aim. To study current approaches to chemoradiation in PMBCL patients with an attempt to individualize them focusing on various prognostic factors. Materials & Methods. The data of 131 patients with newly diagnosed PMBCL were analyzed, all of them were treated at NN Blokhin National Medical Cancer Research Center in the period from 2000 to 2017. More than a half were women (58 %), median age was 30 years (range 16-70). At different historical periods PMBCL treatment was performed using different immunochemotherapy regimens: MACOP-B±R in 55 (42 %) patients, R-CHOP in 40 (30.5 %) patients, and R-DA-EPOCH in 36 (27.5 %) patients. Radiotherapy was used to treat 99 out of 131 patients. Results. In general, the treatment of all PMBCL patients (n = 131) appeared to be highly effective. The remission rate was 87 %, 3-year progression-free survival (PFS) and overall survival (OS) was 78 % and 88 %, respectively. With median follow-up of 37 months relapses and progression of the disease were detected in 17 (13 %) out of 131 patients within a period of 13 months after initiation of antitumor treatment. There was not a single case of late relapse. The treatment of relapsed patients was not effective: 12-month OS was not higher than 37 %. Intensive immunochemotherapy regimens ACOP±R, R-DA-EPOCH) do not differ in their effectiveness, but they have significant advantages over the standard R-CHOP regimen. The results of positron emission tomography (PET) considered to be an important prognostic factor in PMBCL treatment: 3-year PFS in the PET-negative group was 92 % vs. 26 % in the PET-positive group. Conclusion. The optimal algorithm of PMBCL treatment was elaborated with consideration of clinical factors, immunochemotherapy programs, degrees of tumor regression, its metabolic activity, and radiotherapy method and irradiation area.

Aim. To estimate vorinostat efficacy in patients with relapsed/refractory mycosis fungoides and Sezary syndrome. Materials & Methods. The total of 21 patients with refractory and progressive mycosis fungoides and Sezary syndrome receiving vorinostat 400 mg once daily were followed up from 2014 to 2017. The median age was 62 years (range 34–79). The male to female ratio was 10/11. The median number of various regimens of pre-study systemic treatment was 4 (range 1–7). Progressive disease were observed in 85,7 % of patients before administration of vorinostat and after mono- and polychemotherapy. Results. The study group included 15 patients with mycosis fungoides and 6 patients with Sezary syndrome. Early stages of primary cutaneous T-cell lymphoma were diagnosed in 4 patients, the advanced stages in 17 patients. Seventeen patients received vorinostat treatment in monoregime; 4 patients were administered with vorinostat in combination with methotrexate or α-interferon. The median duration of vorinostat therapy was 6 months (range 1–38). Stabilization of the disease was observed in 47.6 % of cases, response to treatment in 38.1 % of cases (with 5 cases of complete response and 3 cases of partial response), and 14.3 % of patients had progression of the disease. The decrease of skin itching was reported in 38.1 % of patients; skin itching completely resolved in 28.6 % of cases. The adverse events required the vorinostat dose adjustment in 3 cases and treatment discontinuation in 3 cases. The total of 9 patients continue to receive vorinostat. Conclusion. Vorinostat treatment was shown to be effective in patients with refractory and advanced mycosis fungoides and Sezary syndrome not responding to various types of external, mono- and polychemotherapy. The therapy with vorinostat was associated with higher life expectancy and improved quality of life.

Mucosis fungoidea (МF) belongs to the class of epidermotropic T-cell lymphomas. MF is represented by over 10 sub-types only in terms of its clinical manifestations, with one of them being erythrodermic MF (EMF). This disease is characterized by diverse symptomatology in the form of erythroderma and intense skin itch, aggressive сlinical course and unfavorable prognosis. The disease prognosis also correlates with age, previous history of long-term systemic gluco-corticosteroid treatment (GCS), increased activity of lactate dehydrogenase (LDH) and hypereosinophilia. The choice of MF treatment is determined by the disease stage and somatic status of the patient. In EMF, a therapy combining various effective preparations and taking into account the specifics of the given case is required. Extracorporeal photopheresis (ECP) is frequently an approach of choice; however, it has demonstrated the highest efficacy in Sezary disease or in EFM associated with leucemization. Application of new pharmaceuticals (monoclonal antibodies, epigenetic agents) in combination or in sequence with immune therapy is a promising direction, particularly for treating patients older than 75 years. In this paper, we describe the clinical case of an elderly patient suffering from EMF without peripheral blood leukemia with multimodal factors of unfavorable prognosis, such as age, increased lactate dehy drogenase activity, history of prolonged inefficient treatment with gluco-cortecosteroid preparations and eosinophilia. A long-term positive response to the treatment using sequential immune epigenetic therapy has not been achieved, although the treatment tolerability and the patient's life quality were satisfactory.

Mucosis fungoidea (МF) belongs to the class of epidermotropic T-cell lymphomas. MF is represented by over 10 sub-types only in terms of its clinical manifestations, with one of them being erythrodermic MF (EMF). This disease is characterized by diverse symptomatology in the form of erythroderma and intense skin itch, aggressive сlinical course and unfavorable prognosis. The disease prognosis also correlates with age, previous history of long-term systemic gluco-corticosteroid treatment (GCS), increased activity of lactate dehydrogenase (LDH) and hypereosinophilia. The choice of MF treatment is determined by the disease stage and somatic status of the patient. In EMF, a therapy combining various effective preparations and taking into account the specifics of the given case is required. Extracorporeal photopheresis (ECP) is frequently an approach of choice; however, it has demonstrated the highest efficacy in Sezary disease or in EFM associated with leucemization. Application of new pharmaceuticals (monoclonal antibodies, epigenetic agents) in combination or in sequence with immune therapy is a promising direction, particularly for treating patients older than 75 years. In this paper, we describe the clinical case of an elderly patient suffering from EMF without peripheral blood leukemia with multimodal factors of unfavorable prognosis, such as age, increased lactate dehy drogenase activity, history of prolonged inefficient treatment with gluco-cortecosteroid preparations and eosinophilia. A long-term positive response to the treatment using sequential immune epigenetic therapy has not been achieved, although the treatment tolerability and the patient's life quality were satisfactory.

T-regulatory cells suppress specific anti-tumor immune responses in non-hematological malignancies and thus lead to tumor growth and unfavorable prognosis. In malignant lymphomas arising from follicular center cells T-regulatory cells are directed not only to cytotoxic lymphocytes but also to tumor B-cells. As in normal lymph node T-regulatory cells can suppress growth and differentiation of germinal center B-cells, and even kill them by cytotoxic mechanism. Generally it may have favourable effect, and lead to the improvement of prognosis in patients. We quantitatively studied FOXP3-positive lymphocytes in different microanatomical lymph node compartments of 66 patients with follicular lymphoma and found favourable influence on prognosis of a large number of intrafollicular FOXP3 cells.

Primary mediastinal (thymic) large B-cell lymphoma is an extranodal lymphoma with primary location of the tumor in the anterior upper mediastinum in fatty and fibrous tissue with or without involvement of the thymus in the malignant process. Seventy-one patients, treated at N. N. Blokhin Oncological Center in 1992-2005 with the diagnosis of primary mediastinal (thymic) large B-cell lymphoma, were examined. Morphologically the tumor was characterized by diffuse proliferation of B-lymphoid cells of different size with different configuration of the nucleus and clear sometimes "empty" cytoplasm. A characteristic sign was stromal sclerosis; islets of residual thymic epithelium were detected in some cases. The peculiarities of immunophenotype include the absence of CD10 expression on malignant cell membrane, expression of CD23 marker in 29% patients, detection of CD38 antigen in more than half of patients, absence or slight expression of HLA-DR molecules in an appreciable part of cases. The results of CHOP treatment were in general unsatisfactory: complete remission was attained in just 13 (25%) of 52 patients, partial in 11 (21%). Three-year relapse-free survival was 37% (median 6 months), total 3-year survival was 52%. On the other hand, treatment by other protocols (MACOP-B/R-CHOP) resulted in antitumor effect in all patients (complete remissions in 58% and partial remissions in 42% patients), but because of little size of the group and short period of observation we cannot consider these differences significant. Primary mediastinal (thymic) large B-cell lymphoma is an individual immunomorphological variant of extranodal non-Hodgkin's lymphoma with a characteristic clinical course and certain routes of dissemination. The methods of first-line therapy choice are MACOP-B or R-CHOP protocols.