Background. Monoclonal antibodies are modern drugs for the treatment of chronic lymphocytic leukemia.

The objective is a comparative study of the monoclonal antibody rituximab efficacy when added to cyclophosphamide + fludarabine (RFC versus FC regimen) in the treatment of chronic lymphocytic leukemia.

Materials and methods. A retrospective study was conducted in Clinical Medical Unit No. 1 of Perm. In total, the response to treatment was analyzed in 22patients (11 patients in each group (FC and RFC therapy)).

Results. Adding rituximab to the FC treatment regimen reduced the number of lymphocytes below 4 х 10 9/L after the 1st course, while maintaining the neutrophil level above 1.5 х 109/L, the absence of anemia (hemoglobin level >130 g/L) and thrombocytopenia (platelet count > 100 х 109/L). An additional assessment of creatinine and uric acid levels showed the absence of tumor lysis syndrome during RFC therapy.

Conclusion. The addition of rituximab (RFC therapy) to cyclophosphamide + fludarabine (FC therapy) provides a more rapid therapy response without adverse toxic effects such as impact on bone marrow functional activity and tumor lysis syndrome.

Currently, phototherapy has been widely used in the treatment of various skin diseases, including mycosis fungoides. The article provides a literature review on the use of various spectra ultraviolet therapy in the treatment of patients with early stages of mycosis fungoides. The mechanisms of action of medium-wave ultraviolet therapy (UVB-311 nm) and PUVA therapy, causing the immunosuppressive, anti-inflammatory and anti-proliferative effect, are described. The results of retrospective studies of PUVA therapy and UVB-311 nm efficacy in patients with cutaneous T-cell lymphoma are presented, as well as modern literature evidence of the need for standardization of phototherapy methods for patients with mycosis fungoides.

A rare case of the multiple myeloma is written. The patient developed the extramedullary lesions with a primary lesion of the duodenum as a massive plasmacytoma with the bleeding, as well as damage to the pancreas and lymph nodes. The patient received several lines of therapy, including proteasome inhibitors and antitumor immunomodulators before the onset of extramedullary lesions. Extramedullary relapse was detected by positron emission tomography combined with CT (PET/CT) before the appearance of obvious clinical signs, which emphasizes the advisability of including PET/CT in the diagnostic algorithm for such patients. Repeated therapy with the previously used bortezomib or lenalidomide was ineffective, there was a further increase in plasmacytoma in duodenum and its bleeding, which led to severe anemia. The combination of carfilzomib with pomalidomide and dexamethasone allowed to achieve complete remission after three cycles of treatment. In this clinical case, we additionally used clarithromycin and metformin to improve the anti-myeloma activity of combination of main treatment. In a brief review of the literature, the frequency of extramedullary lesions, the causes of the appearance of extramedullary lesions, and approaches to diagnosis and therapy are analyzed. Extramedullary lesions with multiple myeloma are a dangerous manifestation of the clonal evolution of the disease, in which the treatment options are still limited, therefore, the demonstration of successful treatment with carfilzomib shows the value of new methods of treatment, as well as the potential effects on the tumor cell when redesigning drug prescriptions.

Objective. The possibilities of ultrasound elastography of the lymph nodes as an additional technique for the intermediate control of treatment of patients with Hodgkin’s lymphoma are determined.

Materials and methods. A prospective study included patients with a diagnosis of classical Hodgkin’s lymphoma with affected superficial lymph nodes. Patients underwent ultrasound elastography (compression elastography and shear wave elastography) of the enlarged lymph nodes before treatment and after two cycles of chemotherapy. The reasons for the ultrasound examination of superficial lymph nodes after the second chemotherapy cycle were: an earlier ultrasound examination with revealed changes in the superficial lymph nodes (in 100% of cases), preservation of the palpable formation in the projection of the superficial lymph nodes (in 56.9% of cases). Before ultrasound elastography of the studied group of patients, the positive dynamics after two cycles of chemotherapy was confirmed by PET/CT (Deauville scale 2—3).

Results and conclusion. According to strain elastography, stiff heterogeneous (third type of elastogram) and stiff structure (fourth type of elastogram) of affected lymph nodes were noted in 53.5 and 42.3% of cases, respectively, before treatment. After two cycles of chemotherapy, these types of elastogram were 52.1 and 43.7% of cases, respectively. According to the results of shear wave elastography before and after treatment, a decrease in the average shear wave velocity in the affected lymph nodes from 2.67 + 0.69 to 2.21 + 0.40m/s (p = 0.000003) was revealed.

Background. Ewing sarcoma (EWS) is a second most common pediatric bone tumor. About one quarter of all patients belong to a high-risk group characterized by a poor prognosis. In spite of high-dose chemotherapy (HDCT) with autologous hemopoietic stem cell transplantation (auto-HSCT) being traditionally viewed as a possible option for high-risk patients, there is stills no consensus on indications for this method in EWS patients.

Study objective: to evaluate the HDCT effectiveness and most important prognostic factors in a prospective cohort of high-risk EWS patients. Materials and methods. A total of 73 EWS patients receiving treatment in R.M. Gorbacheva Memorial Institute were included in the study. All patients were characterized by one or several high-risk features: local (primary tumor volume >200 ml, axial localization, poor response to chemotherapy; n = 55; 76 %), primary disseminated disease (n = 58; 80 %), first chemoresponsive relapse (n = 7; 9 %). All patients received a myeloablative consolidation regimen consisting of busulfan 16mg/kg and melphalan 140mg/m². In patients with primary disseminated disease an additional evaluation according to risk scale by R. Ladenstein et al. was performed. Based on risk points all patients were stratified as standard (n = 20), high (n = 26), and ultrahigh risk (n = 12).

Results. The 5-year overall and event-free survivalfor a whole studied cohort were 40 and 37 %, accordingly. In patients with high-risk localized disease the 5-year overall and event-free survival were 48 and 45 %, accordingly. The HDCT regimen was characterized by acceptable toxicity. The main non-hematologic toxicities were infectious complications (n = 61) and gastrointestinal tract mucositis (n = 31). One patient of 76 died due to treatment-related complications. The multivariate analysis revealed the following risk factors: therapy response (hazard ratio (HR) 2.2; p <0.01), bone marrow involvement (HR 5.0; p = 0.01), primary tumor volume (HR 1.9; p = 0.01), and number of bone metastases (HR 2.2; p = 0.05). The risk group determined by R. Ladenstein score was also a good predictor for outcome with only 8 % of ultrahigh risk patients surviving 5 years past auto-HSCT.

Conclusion. HDCT with auto-HSCT may potentially improve treatment results in some high-risk patient subgroups. While risk scale may help to determine patients most likely to benefit from this approach, the outcome in ultrahigh risk patients are still dismal.

We presented clinical case of invasive candidiasis in 13 years old girl with Ewing's sarcoma during intensive treatment with combined chemotherapy according EWING 2008 protocol. The most significant risk factors were recurrent chemotherapy induced neutropenia gr IV, multifocal Candida colonization, prolonged central venous catheter use, combined antibiotic therapy in the previous >10 days, parenteral nutrition. In spite of provided prophylaxis and antifungal therapy patient died because of progression of invasive candidiasis. We analyzed literature data on frequency of invasive candidiasis in children with Ewing's sarcoma and cases of breakthrough candidiasis in pediatric malignancies.

This article describes a clinical case demonstrating the difficulties of lifetime and post-mortem diagnosis in a patient with primary myelofibrosis complicated by a generalized fungal infection caused by a rare pathogen such as Candida lusitaniae. Management of such patients in non-specialized department with absence of bone marrow trepanobiopsy results associated with the variety of clinical situations in which such manifestations as neutrophilic leukocytosis with left shift without significant changes in the number of erythrocytes and platelets simultaneously with lymphadenopathy and visualizations of secondary foci in internal organs leads to wrong treatment management. And superposition of several pathological processes (granulomatous inflammation, foci of extramedulary hemopoesis and extensive necrotic changes) causes difficulties even for post-mortem verification of the diagnosis, that demonstrate the interest of this clinical case.

Background. Currently, the main treatment for Gaucher disease is enzyme replacement therapy. Recombinant glucocerebrosidase (imiglu-cerase) is the first biotechnological drug for enzyme replacement therapy with proven clinical efficacy and safety for the treatment of patients of different ages with Gaucher disease type 1 and type 3, used in clinical practice since 1994. In Russia, within the framework of the “Pharma 2020” pharmaceutical industry development strategy, the first biosimilar of imiglucerase, the drug Glurazyme®, was developed. The obtained results of preclinical studies became the basis for a phase I randomized comparative crossover clinical trial.

The objective of the study was to assess the short-term safety and pharmacokinetic parameters of Glurazyme® in comparison with the Cerezyme® after a single intravenous administration to healthy volunteers.

Materials and methods. 23 healthy volunteers aged 18—45 years were included in a 3-stage clinical trial. The study during the 1^st and 2^nd stages was open, randomized, comparative, crossover. At the 1^st stage, volunteers from the 1^st group received the Glurazyme®, from the 2^nd group — the Cerezyme® once in doses of 30 U/kg. At the 2^nd stage, Cerezyme® was administered to the 1^st group, Glurazyme® - to the 2^nd group once at doses of 30 U/kg. After the end of the 1^st and 2^nd stages, the 3^rd stage was carried out for the 3rd group (n = 5) with the administration of the test drug once at a dose of 60 U/kg.

Results. For all studied pharmacokinetic parameters, after administration of the test and reference drugs in doses of 30 U/kg, 90 % confidence interval was in the range from 80 to 125 %, which indicates the pharmacokinetic compared drugs equivalence. A total of 6 adverse events of mild and moderate severity were recorded. Of these, 4 adverse events were noted after administration of the study drug and were not associated with its administration. A comparative analysis of safety assessment parameters in this study (frequency and severity of adverse events, physical examination of healthy volunteers with an assessment of vital signs, laboratory tests, electrocardiography) did not reveal intergroup differences.

Conclusion. The pharmacokinetic equivalence of the Glurazyme® and the reference drug in a dose of 30 U/kg has been established. A nonlinear dependence of the main pharmacokinetic parameters on studied drug administered dose was revealed. Safety and the absence of adverse reactions after a single injection of the study drug are shown.

Oncolytic viruses are promising agents for the treatment of various types of tumors, including malignant non-Hodgkin lymphomas. In order to identify the most effective candidates from a wide panel of non-pathogenic antitumor strains, a study was carried out of their ability to reproduce in short-term cultures of lymphoid tumor cells. Also, tumor cell cultures were characterized in relation to the presence of specific viral receptors CD54, CD55, CD155 on their surface.