The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.

Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.

Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.

Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

Background. Currently, overall survival rate for pediatric patients with acute myeloid leukemia (AML) do not exceed 70 %. The intensity of modern AML chemotherapeutic programs has reached its limit, and further chemotherapy dose escalation for treatment results improvement is impossible, because it fraught with life-threatening complications. It is investigating a new ways of tumor treatment for improvement of AML patient’s survival level: therapeutic efficacy of targeted and epigenetic drugs.

Objective: to evaluate the efficacy of epigenetic drugs (azacitidine, decitabine, all-trans-retinoid acid and valproic acid) in combination with AML-BFM 2004 protocol for treatment of pediatric AML.

Materials and methods. 80 patients with primary AML diagnosis were enrolled the study. Age was ranged from 8 months to 17 years (median 6.7 ± 0.6 years). From June 2012 to January 2018 all patients were subdivided in two treatment groups. 1st group included 34 patients treated with NII POH AML 2012 protocol, 2nd group – 46 patients treated by AML-BFM 2004 protocol.

Results. 3-year relapse-free survival in 1st group, regardless of prognostic risk group, was 66.7 ± 11.7 %, 2nd group – 68.9 ± 9.9 %. Eventfree survival (EFS) for patients from 1st group was 66.7 ± 11.7 %, form 2nd group – 50.4 ± 10.2 %. Overall survival in 1st group was 66.7 ± 14.3 %, 2nd group – 66.9 ± 7.5 %. For patients with unfavorable risk from 1st treatment group 3-year relapse-free survival was 69.1 ± 11.9 %, 2nd – 64.9 ± 11.3 % (p = 0,8). EFS – 69.1 ± 11.9 and 44.8 ± 11.3 % respectively (p = 0,13). 3-year overall survival for patients with unfavorable risk group was 69.4 ± 14.6 and 64.4 ± 7.9 % in 1st and 2nd treatment groups respectively.

Conclusion. The efficacy of decitabine in “window” regimen was higher in contrast to azacitidine; epigenetic therapy with AML-BFM 2004 protocol allow us to achieve a higher EFS, because of induction mortality and infection-related death decrease – EFS in 1st group was 16 % higher than in 2nd. Besides, EFS in unfavorable risk group, who treated with epigenetic drugs, was 25 % higher – 69.1 ± 11.9 % and 44.8 ± 11.3 % in 1st and 2nd groups respectively (p = 0.13). Nevertheless, overall survival in both groups was the same – 66 % (1st – 66.7 ± 14.3 % and 2nd – 66.9 ± 7.5 %).

The prognosis for patients with multiple myeloma has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens, and improved management of toxicities. Treatment of relapsed or refractory multiple myeloma represents a vital aspect of the overall care for patients with multiple myeloma and a critical area of ongoing biologic and clinical research. The choice of regimen at relapse is usually based on the prior response, toxicities, assessment of prognostic factors, age and comorbidities of individual patients, their somatic condition and expected effectiveness and tolerability. The new drugs, such as ixazomib, carfilzomib, pomalidomide, daratumumab and elotuzumab in combinations in doublet or triplet regimens, have greatly increased the treatment armory against myeloma. Long-term continuous therapies as a new strategy for relapsed or refractory multiple myeloma have been shown to provide an eradicating of minimal residual disease and deep prolong responses, with the goal of improving progression-free survival and overall survival. The integration of novel agents into the treatment paradigm has shifted the perception of multiple myeloma from an incurable fatal disease to a manageable chronic one. This review discusses the most recent and effective regimens for the relapsed or refractory multiple myeloma treatment, based on the results of recently published phase II and III clinical trials. Analyses the current clinical trial data discussed with a focus on lenalidomide or bortezomib as a basis of new treatment regimens.

The objective: to evaluate the possibilities of ARFI technology (Acoustic Radiation Force Impulse), including Virtual Touch™ Tissue Imaging (VTI) and Virtual Touch™ Tissue Quantification (VTQ) for differentiation of lymphomatous and metastatic superficial lymphadenopathy.

Materials and methods. The prospective study included 138 patients with enlarged superficial lymph nodes (LN). Based on a previous histological examination, patients were divided into two groups: 1st group (n = 108) – patients with non-Hodgkin’s lymphomas and Hodgkin’s lymphoma; 2nd group (n = 30) – patients with metastasis of solid tumors in superficial LN. All patients underwent ultrasound elastography of the enlarged LN using ARFI technology. In VTI study the Area Ratio parameter was evaluated, and the minimum and average values of the shear wave velocity were estimated in VTQ study.

Results. According to the results of VTI study the Area Ratio parameter for enlarged LN in lymphoma (1st group) and for metastatic lymphadenopathy (2 nd group) were 1.031 ± 0.197 and 0.851 ± 0.15, respectively (p = 0.000009). The cut off value of the Area Ratio parameter was 0.901 with sensitivity, specificity and accuracy 80.6, 70.0 and 78.8 %, respectively. Minimum values of shear wave velocities for 1st and 2 nd groups were 1.980 ± 0.557 and 2.214 ± 0.367 m/s, respectively (p = 0.032). The cut off values of the average shear wave velocity in the differentiating of lymphomatous and metastatic lymphadenopathy are determined at the level of 2.00 m/s, with sensitivity of 70.0 %, specificity of 59.3 %, and accuracy of 61.6 %.

Conclusion. Ultrasound elastography with ARFI technology demonstrated statistically significant differences in the Area Ratio parameter and in the minimum shear wave velocity in the enlarged superficial LN in lymphoma and with metastasis that can be used as a preliminary non-invasive differential diagnosis of enlarged superficial LN in these conditions. Moreover, the Area Ratio parameter has a statistically more significant effect on differentiating of lymphomatous and metastatic lymphadenopathy.

The pathogenetic relationship of kidney damage and an aberrant clone of the B-cell line producing nephrotoxic monoclonal immunoglobulin underlies the concept of “monoclonal gammopathy of renal significance” (MGRS). Herein the aberrant clone does not reach the criteria necessary for initiating antitumor therapy according to oncohematological indications. MGRS is a new nosology in modern nephrology and oncohematology. Monoclonal protein’s pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: i) limited knowledge about the MGRS among hematologists and nephrologists; ii) lack of necessary diagnostic resources in most health-care facilities; iii) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. In order to overcome these limitations, leading oncohematologists and nephrologists of the Russian Federation on behalf of professional communities at the end of 2019 published a conciliation document: “Monoclonal gammopathy of renal significance: Consensus of hematologists and nephrologists of Russia on the establishment of nosology, diagnostic approach and rationale for clone specific treatment”. Consensus document comprises the opinion of experts – leading nephrologists and hematologists of Russian Federation – on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia “Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy”, 15–16 of March 2019, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia. Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses which we present here.

Erdheim–Chester disease (ECD) is a rare and frequently neglected disease, usually with a poor prognosis. The first two cases of ECD were reported by Austrian pathologist: Jakob Erdheim and his apprentice student William Chester in 1930. The etiology and disease incidence are unknown. One of the main components of this disorder is a chronic uncontrollable inflammation. Clinical manifestations of the disease can be very different. ECD affects predominantly adults, usually male population. There is no effective treatment developed yet. In 2016 ECD was classified as histiocytic neoplasm by the World Health Organization and was categorized as “tumors of histiocytes and dendritic cells”. More than half of patients testing positive for the BRAF mutation. There is a Erdheim–Chester Disease Global Alliance (ECDGA), which try to unite and provide with information about diagnostics and treatment of this rare disease both patients and doctors. Today, there are 571 registered patients and only one from Russia. The final diagnosis is made on the basis of histological finding such as infiltration with foamy histiocytes, signs of inflammation and Touton giant cells. Immunohistological analysis is usually CD68 and XIIIa positive. There are radiological finding indicating a possible association with the disease. There is this specific, almost pathognomonic scintigraphic picture of the skeleton, “coated” aorta, “hairy kidney” patterns on computer tomography. We demonstrate a clinical case of a patient with a newly diagnosed ECD with bone and connective tissue involvement, with manifestation of this disease more than 10 years ago. It took four months to make the final diagnosis. There were three biopsies and a wide range of other diagnostic procedures.

Background. A violation of nutritional status (obesity) and emotional-behavioral status (depression) is one of the urgent problems of modern health care. Often these two problems are at the same time. Particularly striking manifestations of a decrease in nutritional and emotional statuses are observed in children with oncological diseases of various origins.

Objective: to assess the emotional-behavioral status and nutritional status in pediatric cancer and hematological diseases after treatment.

Materials and methods. The study included 112 children with acute lymphoblastic leukemia (n = 49) and central nervous system tumors (n = 63) in remission. Age 6–18 years (median 11.5 years). 66 male (58.9 %). The Aachenbаch questionnaire was used to assess the behavioral and individual-personality characteristics. CDI (children depression inventory) questionnaire was used to assess the presence and level of depression. Body mass index (in percentile terms) and body tissue composition by bioimpedance analysis (body fat and lean body mass were evaluated) were used to assess nutritional status.

Results. As a result, it was found that a significant proportion of children have delayed effects of treatment in the form of reduced nutritional status and emotional and behavioral difficulties. Children with brain tumors have an increased risk of nutritional and emotional-behavioral disorders compared to children who have survived acute lymphoblastic leukemia. The nutritional and emotional-behavioral statuses of children are related: the presence of excess fat mass increases the risk of emotional-behavioral disorders. According to questionnaires, parents identify detected problems much more often than patients themselves.

Conclusion. In children who have experienced antitumor treatment and achieved remission, in case of excess body fat, the risk of emotionalbehavioral disorders increases. Emotional-behavioral disorders can have a negative effect on rehabilitation measures; therefore, before starting rehabilitation measures it is necessary to take into account the nutritional and emotional-behavioral status of patients.

Background. There are problems related to both quantitative assessment of an allele burden level of a mutant gene and interpretation of results in DNA samples with the burden level of the mutant allele less than 15–20 %, when using Sanger sequencing for analyzing somatic mutations. Applied Biosystems (USA) has developed new software Minor Variant Finder, which allows determining mutations with the allele burden level from 5 %.

The objective: to determine the allele burden level and identification of minor variants of somatic mutations in the ASXL1, JAK2 genes and BCR-ABL oncogene using Minor Variant Finder software in patients with myeloproliferative neoplasms.

Materials and methods. The level of mutant allele burden for 15 patients with myeloproliferative neoplasms was determined by the identified mutations using the Minor Variant Finder software, after analysis of point somatic mutations in the ASXL1, JAK2 genes and BCR-ABL oncogene by Sanger sequencing.

Results. The allele burden level in all 5 ASXL1-positive samples and BCR-ABL-positive sample was determined as higher than 20 % using the Minor Variant Finder software. The allele burden level in 2 cases was higher than 20 % and in 7 cases lower than 20 %, when we analyzed 9 JAK2-positive samples.

Conclusion. Minor Variant Finder software can be used to estimate the allele burden level and to identify minor variants of somatic mutations in the ASXL, JAK2 and BCR-ABL genes.

Infections are a common complication in patients with hematological malignancies, especially during neutropenia. Recently, an increase in multidrug-resistant gram-negative pathogens has been observed in the etiology of infectious complications, including carbapenem-resistant Enterobacteriaceae. However, therapeutic options for treatment of these infections are limited. The review represents treatment options for infections caused by carbapenem-resistant Enterobacteriaceae, including the use of reserve drugs such as polymyxin, carbapenems, tigecycline, as well as a new antibiotic – ceftazidime-avibactam, which contains a new β-lactamase inhibitor with unique properties.