Background. Secondary malignancies in pediatric cancer survivors is an actual problem in modern oncopediatry. Alkylating agents and topoisomerase II inhibitors used for primary tumors treatment, induce secondary acute myeloid leukemia (sAML), which treatment results are unsatisfactory.

Objective. By predicating on literature and own data to evaluate clinical and biologic features and therapeutic potential of pediatric sAML.

Materials and methods. Six patients (age 7–16 years) with sAML were enrolled the study from June 1998 to December 2016. Follow up until September 2020. Primary tumors, which therapy could induce sAML were acute lymphoblastic leukemia, Burkitt lymphoma, germ cell tumor, osteosarcoma, nephroblastoma.

Results and conclusion. From 6 patients, included in the study, 2 are alive (+58 and +67 months after allogenic stem cell transplantation), that match global data. Fludarabine-containing regimens and allogeneic hematopoietic stem cell transplant could be a method of choice for this unfavorable group of patients.

Background. Splenic marginal zone lymphoma (SMZL) is an indolent non-Hodgkin’s B-cell lymphoma. It presents morphologically by mature lymphoid B-cells. They conform to these immunological characteristics of marginal zone lymphocytes from secondary follicles. The tumor B-cells of SMZL do not have specific markers of immunophenotype and requires the exclusion of other non-Hodgkin’s B-cell lymphomas. There is an annual increase in the incidence of SMZL. There are refractory forms and progressive course of the SMZL. There is a huge variety of the mechanisms of evading tumor cells from immunological control. Unlike solid tumors, B-lymphoproliferative diseases are characterized by the expression of HLA I/II and co-stimulatory molecules (CD80 and CD86). Therefore, tumor B-lymphocytes can act as antigen-presenting cells (APC) for T lymphocytes. The T-cell immune response is known to play an important role in antitumor control. It is known that effective activation of T-lymphocytes requires the formation of an immunological synapse and the presence of two activation signals (antigen recognition and co-stimulation of CD28-CD80/86). According to the modern concept of tumor development, there is a gradual selection of tumor clones. As a result, only tumor cells that are invisible to the immune system remain. Mechanisms of evasion of tumor B-cells of SMZL from immune surveillance are currently not fully understood and are being actively studied.

Objective: to study the expression features of antigens involved in the formation of immunological synapse in patients with SMZL in peripheral blood.

Materials and methods. The study includes 10 primary SMZL patients; all patients have stage IV according to the Ann Arbor classification. Splenectomy was performed for all patients as a first stage of treatment. Two patients had progression of SMZL after splenectomy, which required chemotherapy. The control group included 25 healthy donors. Peripheral blood was used as a material for analysis. The study was conducted on a 6-color BD FACS Canto II flow cytometer (BD Biosciences, USA) immediately after diagnosis.

Results. Tumor B-cells of SMZL are different from B-cells of healthy donors with a greater proportion of CD80⁺, FAS⁺, PD-1⁺-cells, which may correspond to activated B-cells. The proportion of CD4+PD-1+ and CD8⁺PD-1⁺ T-cells in patients with SMZL was higher in comparison with the control group. There was a large proportion of T-cells expressing PD-1 in the group of patients with SMZL progression after splenectomy in comparison with the group of patients with indolent course of SMZL. Conclusion. Thereby, tumor B-cells of the SMZL retains the features of non-tumor analogues. The most significant mechanism for evading immune surveillance in an SMZL is inhibition of the T-cell immunity via the PD-1–PD-L1 pathway. The most pronounced inhibition of T-cell immunity causes an uncontrolled tumor process.

Group of tumor-associated antigens, which is normally expressed in placental cells and testicular germ cells, is called cancer-testis antigens. To date, more than 40 gene families have been identified that encode cancer-testis antigens, and their expression has been studied in many types of malignant diseases. It is assumed that the expression of cancer-testis antigens can contribute to the development of the tumor transformation process, including hematological diseases. Of particular interest in the pathogenesis of multiple myeloma is the MAGE-C1/CT7 antigen, the expression of which is most often detected in this case. According to data published by various authors, the expression of MAGEC1 in multiple myeloma can be considered as an additional marker of a poor disease prognosis, represent the effectiveness of chemotherapy approaches, and, possibly, be an earlier predictor of relapse or progression.

The article provides a literature review about RHD and RHCE polymorphisms which encode different RhD and RhC antigen variants. The data about genes RHD and RHCE polymorphisms, RhD weak types, RhD partial types and RhC variants in Russians is presented for the first time. The molecular and serological characteristics of rare RhD and RhC antigens are summarized. The role of serological and molecular methods in Rhesus system antigens identifying is shown.

Background. Secondary hemophagocytic lymphohystiocytosis (sHLH) is a hyperinflammatory reaction provoked by some trigger (cancer, autoimmune or infection). The majority of affected patients are at high risk of fatal multiple organ failure without getting immunsupressive treatment.

Objective. Clinical and laboratory profile of sHLH patients.

Materials and methods. Retrospective study included clinical, instrumental and lab data from the 91 patients followed between June 2009 and June 2019. Diagnosis sHLH had been based on HLH-2004 and H-Score criteria. The analyzed parameters had been fever chart, liver and spleen enlargement, changes in the bone marrow; values levels of glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, bilirubin, triglycerides, total ferritin with percentage of glycosylation. All patients with rheumatic disorders or malignancies had received either immunosuppressive or cytotoxic therapy. Febrile patients received anti-infective treatment according to the local routine protocols.

Results. The data from 91 patients (41 male and 50 female) had been analyzed. Median age was 58 (2–90) years. The sHLH trigger-diseases spectrum included leukemia/lymphoma (n = 52), infection diseases (n = 11), autoimmune disorders (n = 5), allogenic bone marrow transplantation (n = 13), unidentified (n = 10). A fever with an unknown origin and refractory to antibacterial treatment had been observed in 87 (96 %) patients. Morphological hemophagocytic evidences in the bone marrow had been found in 83 %. Breath shortening, liver failure, neurologic disturbances, systemic effusions, rash, heart failure had been registered in 83 % patients. Detected splenomegaly presented in 56 %. Laboratory changes, median were as following: serum glutamic-pyruvic transaminase (alanine aminotransferase, SGPT) – 92 (39.2–1060.8) IU/L; serum glutamic oxaloacetic transaminase (aspartate aminotransferase, SGOT) – 105 (40–4177) IU/L; alkaline phosphatase – 225 (120.9–989) IU/L; bilirubin – 50.5 (22–559) µmol/L; triglycerides – 3.2 (1.95–8.6) mmol/L; total ferritin – 10000 (597–255000) ng/mL with glycosylation percentage – 20.45 (0–37.8) %. 71 patients received various of HLH-directed therapy courses. The overall survival rate was 27 %, median follow-up – 540 days.

Conclusion. The main clinical and instrumental findings in sHLH are fever, refractory to anti-infective treatment, elevation of transaminases, serum alkaline phosphatase, triglycerides, total ferritine with low glycosylated fraction. Early diagnosing and immunesupression are the main factors of survival.

Background. In modern oncohematology achieved notable success due to the intensification and development of new chemotherapy regimens. However, the side effects of anticancer drugs, due to low selectivity of most of them, are a serious limitation to achieve their maximal therapeutic effect. Although doctors are aware of the possibility of hepatotoxic reactions to various drugs, in clinical practice, the diagnosis of drug-induced liver injury is formulated unreasonably rarely. This speculation is due to several factors: in some cases, the latent course of drug-induced liver injury, often inadequate interpretation of clinical symptoms and laboratory parameters, and sometimes insufficiently thorough collection of anamnesis. A particularly difficult problem for a doctor is the development of drug-induced hepatotoxicity in patients for whom the “causal” drug is prescribed for vital indications, in particular, polychemotherapy in cancer patients, complex antimicrobial therapy and antiviral therapy for febrile neutropenia or sepsis, etc. In these situations, on the one hand, treatment cancellation is impossible due to the risk of disease progression, on the other hand, its continuation is undesirable due to the risk of severe hepatitis. In addition, multicomponent therapy, which is a complex of potentially hepatotoxic substances, often does not allow specifying the substance that caused the pathological reaction. At the same time, it is obvious that the hepatocyte, the main cell of the hepatic parenchyma, remains the center of the organ pathology. The variety of biochemical processes occurring with ademetionine participation served as the basis for conducting clinical studies in order to correct drug-induced liver toxicity in the treatment of patients with blood system tumors.

The objective of the study is to assess laboratory and clinical parameters of drug-induced liver injury (DILI), intrahepatic cholestasis in the study of homeostasis disorders in patients with hematological malignancies and chemotherapy-induced hepatotoxicity.

Materials and methods. The study involved 45 patients with blood system tumors, who had chemotherapy-induced hepatocellular failure. To describe the population of DILI patients, we collected demographic data, clarified the underlying liver disease in each patient, and analyzed the diagnostic criteria for chronic liver disease due to DILI. Clinical signs and symptoms of cholestasis (jaundice, pruritus, weakness), as well as manifestations of a depressive state and asthenic syndrome – mood (mild, moderate and severe), normalization of sleep rhythm, memory improvement, general health were assessed. Changes in laboratory parameters of liver function were studied. In 20 patients with blood system tumors, the biochemical parameters associated with cell metabolism were analyzed – lipid peroxidation, nitric oxide (NOx ) level, impaired liver detoxification capacity by glutathione level and glutathione-S-transferase activity. The treatment regimens for drug-induced hepatotoxicity included the Heptral, which was prescribed until stable normalization of liver function.

Results. All patients with developed liver failure showed metabolic disorders. The use of ademetionine has shown significant effect. The NO and superoxide dismutase in most patients decreased significantly and almost corresponded to the norm. Normalization of the glutathione system parameters was also observed. One of the mechanisms of Heptral protective effect is an increase in the glutathione synthesis. The improvement in laboratory parameters was accompanied by the disappearance of DILI and intrahepatic cholestasis symptoms. This is confirmed by significant statistical correlations between them and indicates the ademetionine efficacy to recovery of hepatocytes function. When using ademetionine, the most pronounced reduction among biochemical parameters was observed in alkaline phosphatase and γ-glutamyl transpeptidase, markers of cholestasis syndrome. In addition, serum bilirubin concentration and alanine and aspartic transaminases activity (albeit to a lesser extent) decreased significantly. Clinical and biochemical effects, as a rule, persisted for several months after completion of therapy. Decrease in biochemical parameters characterizing cholestasis and cytolysis (positive dynamics of alanine and aspartic transaminases, alkaline phosphatase, γ-glutamyl transpeptidase, bilirubin) was accompanied by an improvement and normalization of patients’ well-being. When assessing the depression and asthenic syndrome, it was noted that the duration of Heptral therapy is important.

Conclusion. The results obtained were the basis for the development of supportive therapy programs to prevent and reduce liver toxicity during chemotherapy. Rational approaches to the liver metabolic disorders correction – a real way to increase the treatment efficacy and improve the quality of life of patients with blood system tumors.

Objective: to study the importance of cytokines, hepcidin, a soluble transferrin receptor, iron metabolism in the development of anemia of chronic diseases in patients with malignant neoplasms and rheumatic pathology, to identify the leading factors in the development of anemia for each of the studied groups and to develop a working classification of anemia of chronic diseases.

Materials and methods. 63 patients with rheumatic pathology were examined. The study group included 41 (17 men/24 women, average age 53.4 ± 4 years) patients with anemia, the control group included 22 (9 men/13 women, age 49.3 ± 1.78 years) patients without anemia. The patients (n = 63) with stage II–IV malignant neoplasms were examined. The study group included 41 patients with anemia (34 men/7 women, age 67.1 ± 9.9 years), in the control group 22 patients without it (17 men/5 women, age 60.2 ± 14.9 years). The number of red blood cells, the hemoglobin level, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, concentrations of serum iron, total iron binding capacity (TIBC), ferritin, transferrin, C-reactive protein (CRP), transferrin saturation index (TSI), and soluble transferrin receptor (sTfR), hepcidin, interleukin (IL) – 6, – 10, tumor necrosis factor-α (TNF-α) were determined. Mann – Whitney U Test was applied to check for statistically significant differences in study samples.

Results. Compared with the control group, elevated concentrations of ferritin, CRP, hepcidin, sTfR and IL-6 (p <0.05) were found for patients with rheumatic pathology and anemia and no differences were found in the concentrations of iron, TIBC, TSI, transferrin. For patients with solid malignant neoplasms and anemia, lower concentrations of iron, TIBC, TSI and higher concentrations of CRP, hepcidin, sTfR, IL-6, IL-10, TNF-α (p <0.05) are shown in comparison with the control group and there were no differences in the concentrations of ferritin, transferrin (p >0.05).

Conclusion. The multicomponent anemia genesis in patients with cancer and rheumatic pathology is shown. The contribution of each mechanism to the development of anemia may vary depending on the specific nosological form. In patients with cancer, functional iron deficiency, activation of IL-6, IL-10, TNF-α synthesis and an increase in hepcidin synthesis lead to the development of anemia of chronic diseases. In patients with a rheumatic profile and anemia, a more pronounced synthesis of hepcidin and an increase IL-6 concentration are indicated. A working version of the classification of anemia of chronic diseases based on the leading pathogenetic factor is proposed (with a predominant iron deficiency, with impaired regulatory mechanisms of erythropoiesis, with insufficient production of erythropoietin).

Background. Modern standards for the treatment of both solid tumors and tumors of the blood system provide a mandatory assessment of the objective status of the patient. One of the important criteria of which is nutritional status. Underestimating the role of nutritional support in the treatment of cancer patients leads to a deterioration of treatment results due to the progressive deterioration of nutritional status and the development of cancer anorexia cachexia syndrome (CACS), which is an independent adverse factor leading to the death of the patient. The increase in the number of cancer patients with risk factors for CACS development requires not only close attention of clinicians to this problem, but also the development of clear recommendations for the diagnosis and management of such patients. This can contribute to solving several problems at once. First, it will allow optimizing monitoring of cancer patients predisposed to CACS development during anticancer treatment. Secondly, it will provide an opportunity to develop a diagnostic algorithm to prevent it. Third, the use of the identified criteria for predicting and outcome of complications both on an outpatient basis and in a hospital will be aimed at creating favorable conditions for anticancer therapy and thereby improving long-term treatment results and patients quality of life. Studying the mechanisms of development of CACS, the possibilities of correcting this condition, indicate the need for a multimodal concept and the rejection of the search for a “magic pill”. The results of a multicenter, prospective randomized study conducted in the oncology and hematology departments of healthcare institutions.

Objective: to evaluate the effectiveness of FortiCare oral nutritional support in cancer patients under the real clinical practice.

Materials and methods. The study included 96 patients with stage II–IV tumors. Radiation therapy was received by 28 patients, chemotherapy ‒ by 68 patients. Patient information was collected using an individual registration card. The patients were randomized according to nutritional support tactics (1:1). In the study group, with radiation (n = 14) and chemotherapy (n = 34), patients received enteral nutrition Forticare orally 125 ml 3 times a day in parallel with their usual diet. Patients in the control group during radiation therapy (n = 14) received the required amount of calories from their usual diet. During chemotherapy, patients in the control group (n = 34) with a lack of daily calorie intake received additional parenteral nutrition.

Results and conclusion. While taking FortiCare, there was a smaller loss of body weight (p ≤0.05), a frequency of mucositis of the oral cavity, and esophagitis (p >0.05). With chemotherapy, the incidence of diarrhea (p <0.001) and constipation (p <0.05) was detected less frequently than in the control group. A decrease in the frequency of hematological toxicity (leukopenia, thrombocytopenia) was noted (p >0.05).

Background. In the Russian Federation, in 2018 3,207 new cases of Hodgkin’s lymphoma (HL) were detected, mainly in adults. Despite significant advances in the treatment of this disease, approximately 20–30 % of patients develop relapses. High-dose chemotherapy with autologous hematopoietic stem cell transplantation is the standard 2nd line therapy. Patients with relapse after autologous hematopoietic stem cell transplantation have a poor prognosis. Brentuximab vedotin, nivolumab, and pembrolizumab are indicated for treatment of relapsed HL after autologous stem cell transplantation.

The objective of this study is to conduct budget impact analysis of increasing the share of patients with relapsed HL, who are treated with brentuximab vedotin.

Materials and methods. We estimated medication costs of using brentuximab vedotin, nivolumab, and pembrolizumab based on clinical trials data. The number of patients who annually start treatment using these alternatives was determined using data on purchases of drugs by public health funds in 2019. Budget impact was defined as the difference in public health expenditures on medications in case of increase in brentuximab vedotin share by 10 or 20 percentage points compared to current practice, with a proportional decrease in the share of patients, who receive nivolumab or pembrolizumab. Time horizon was 6 years.

Results. Expenses for treatment of a single patient with relapsed HL within 6-year study horizon using brentuximab vedotin (7.07 million rubles) were 2.15 million rubles less than in case of treatment with nivolumab, and 4.38 million rubles less than for pembrolizumab. There are 295 patients with relapsed HL, who start treatment with brentuximab vedotin, nivolumab or pembrolizumab annually. If the proportion of patients, who start therapy using brentuximab vedotin, increases from the current 60 % to 70 %, cost savings over 6 years will be 171 million rubles, which corresponds to extra 24 patients who can be treated using brentuximab vedotin without increasing budget expenditures. If the proportion of patients with relapsed HL receiving brentuximab vedotin increases to 80 %, savings in public health funds over 6 years will amount to 341 million rubles, which allows treating 48 additional patients with brentuximab vedotin without budget increase.

Conclusion. Brentuximab vedotin is a cost-saving treatment option of relapsed HL, compared to nivolumab and pembrolizumab. Increasing share of patients, who receive brentuximab vedotin, allows treating additional patients without increase in public health budget.