Primary lymphoma of the central nervous system (PLCNS) is a rare form of extranodal lymphoma characterized by an aggressive course. In recent decades, the treatment of this disease has undergone significant changes. Modern treatment of PLCNS consists of two steps – induction and consolidation of remission. Improved overall survival of PLCNS patients was achieved through the use of combined immunochemotherapy regimens with high doses of methotrexate and/or cytarabine, which are currently the standard of induction therapy. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation at the consolidation stage provides the most complete elimination of the residual tumor clone. The most effective modes of conditioning are those with the inclusion of tiotepa. In elderly and comorbid patients who are not candidates for autologous hematopoietic stem cell transplantation, promising results were obtained while using maintenance therapy with procarbazine or temozolomide, and further researches will allow us to study the effectiveness of monocolonal anti-CD20 antibodies – rituximab and obinutuzumab.
Treatment options for patients with relapses and / or refractory forms of PLCNS are limited. Certain successes were obtained with the use of new drugs – ibrutinib, nivolumab, lenalidomide, obinutuzumab.

Nowadays due to modern risk-adapted treatment protocols high survival rates have been achieved in patients with aggressive B-cell lymphomas, even at stages III–IV these indicators overrun 90 %. Mainly these successes were associated with the inclusion of rituximab in the standard chemotherapy regimens. As the follow up period of the patients is lengthened, it has become clear that ongoing treatment is associated with the development of immediate and long-term adverse effects of chemoimmunotherapy. In Russia and the world, there are multicenter studies aimed at studying prognostic factors that make it possible to reduce single and/or total doses of chemotherapy drugs, and therefore, to reduce chemotherapy toxicity. The obtained data allow considering the early complete antitumor effect (after 2 courses of therapy) as an advantage factor, so it is possible to reduce program chemoimmunotherapy intensity without reducing high patients survival rates.

Objective. Comparative evaluation of the effectiveness and toxicity profile of intensified chemotherapy regimens BEACOPP escalated (esc.), BEACOPP-14 and EACOPP‑14 in primary patients with classical Hodgkin’s lymphoma of an unfavorable prognostic group.

Materials and methods. The study included 149 patients: 84 women (56 %) and 65 men (44 %) with a newly diagnosed classic Hodgkin’s lymphoma, who received antitumor treatment in the Department of high-dose chemotherapy with a bone marrow transplantation unit at the Р. A. Hertzen Moscow Oncology Research Institute from 2006 to 2018. The median age was 31 years (17–69). The majority of patients were diagnosed with Hodgkin’s lymphoma nodular sclerosis (88.6 %). All patients belonged to an unfavorable prognostic group, despite the fact that more than 1/3 of them had local stages of the disease. The most frequent adverse factors identified in the majority of patients were: massive lymph node lesion (bulky disease) – in 111 patients (74.5 %), B-symptoms – in 84 (56.4 %), increased erythrocyte sedimentation rate – in 55 (36.9 %), extranodal lesion – in 105 (70.5 %), including bones and bone marrow – in 10 (6.7 %) and 14 (9.4 %), respectively. Antitumor treatment was performed under the BEACOPP program in the following modifications: BEACOPP‑14 – 94 (63.1 %), EACOPP-14 – 32 (21.5 %), BEACOPP-esc. – 23 patients (15.4 %). Consolidating radiotherapy was performed in the majority of patients – 132 (88.6 %).

Results. After the chemotherapy, remission of the disease was achieved in 141 patients (94.6 %), a complete response was in 101 of them (67.8 %). The immediate antitumor effect was more expressed when using the program BEACOPP‑14 (in 72.3 %), compared to EACOPP‑14 and BEACOPP-esc. (in 59.4 % and 60.9 %, respectively).

Chemotherapy resistance was observed in 8 patients (5.4 %). Chemotherapy results were improved in combination with radiation therapy in 40 patients (26.8 %). After the end of chemoradiotherapy, complete remissions were achieved in more than 93.6 % of patients. Relapses occurred in 8 patients: early – in 3 (2.1 %) and late – in 5 (3.5 %). Four patients died (2.7 %): 1 – from disease progression, 2 – from resistant relapse, and 1 patient from other causes.

With a median follow-up of 46 months, the 5-year overall survival rate was more than 93.7 %, event-free-more than 83 %, and relapse-free – 90.3 % or more. When evaluating long-term treatment results depending on the induction chemotherapy program, the outcome was better when using the BEACOPP-esc. in comparison with EACOPP‑14 and BEACOPP‑14. The most frequent myelotoxic complication – more than 90 % – on all chemotherapy programs was deep leukopenia. Thrombocytopenia III–IV degree developed more often on the BEACOPP-esc. (in 52.2 %), severe anemia – on EACOPP‑14 (in 44 %). Among infectious complications, mucositis prevailed and was most often observed on BEACOPP-esc. (in 74 %). Febrile neutropenia and herpetic infection developed less frequently, mainly in the BEACOPP-esc. and EACOPP‑14 program. Another serious complication was pneumonia, which was more frequently reported during BEACOPP‑14 (18.1 %). Secondary tumors, as a later complication, were less likely to be detected in the treatment program BEACOPP‑14 (1 %), compared to BEACOPP-esc. and EACOPP-14 (4.3 % and 3.1 %, respectively).

Conclusion. All modifications of the BEACOPP program showed good direct effectiveness. However, the best long-term results, despite slightly more expressed toxicity, were noted on the BEACOPP-esc. program.

Cytopenia commonly occurs in case of chronic lymphocytic leukemia. It can either precede the diagnosis of chronic lymphocytic leukemia or appear at any time during the disease. Autoimmune hemolytic anemia, immune thrombocytopenia, and partial red cell aplasia are most often found among cytopenias in chronic lymphocytic leukemia. At the same time, the development of cytopenia may be associated with the displacement of normal hematopoiesis cells by tumor lymphocytes. It is very important to accurately diagnose and identify the cause of cytopenia in chronic lymphocytic leukemia, since the prognosis and therapy differ significantly.

Background. In accordance with the World health organization clinical guidelines, the analysis of somatic mutations in the CALR gene, as well as mutations in the JAK2 and MPL genes, are included in the list of criteria for the Ph-myeloproliferative neoplasms diagnosis.

More than 50 different mutation variants have been found in the CALR gene, among which the most frequent are a 52 bp deletion (c.1092_1143del), also called type 1, and a 5 bp insertion (c.1154_1155insTTGTC), also called type 2 (88 %).

The remaining 12 % are other type less frequent indels or combinations thereof.

It is most convenient to use sequencing methods to identify all possible variants of CALR mutations. It is also important to develop inexpensive screening test that can detect any mutations in the analyzed DNA fragment of CALR gene. This method can be heteroduplex analysis followed by electrophoresis on polyacrylamide gel (PAGE).

The objective: to develop and demonstrate the feasibility of using heteroduplex analysis with separation of the PCR product by electrophoresis on non-denaturing PAGE for the CALR exon 9 mutations detection as the screening test. Materials and methods. DNA samples of 13 CALR-positive patients with different phenotypic variants of Ph-myeloproliferative neoplasms were screened by heteroduplex analysis. For the most common variants of CALR mutations (c.1092_1143del and c.1154_1155insTTGTC), a threshold determination of the mutant allele presence was analyzed.

Nucleotide sequence of exon 9 fragment was determined using Sanger sequencing. Also, all 13 samples were analyzed using the pyrosequencing method to assess the allelic burden level.

Results. Heteroduplex analysis revealed mutations in exon 9 of the CALR gene in all 13 patients. The threshold determinations of the method in the case of the c.1154_1155insTTGTC and c.1092_1143del analysis are 6.25 % and 3.13 % of the mutant allele presence in the patient sample, respectively.

Conclusion. The proposed variant of the heteroduplex analysis with separation of the PCR product by electrophoresis on non-denaturing PAGE can be recommended for use as the preliminary screening test which is carried out before the confirming sequencing methods for the different indels (or combinations thereof) CALR mutations determine.

The presence of heteroduplexes indicates the presence of a mutation, even if the mutant product is not visualized (in case of small mutations).

Background. Genetic instability, an important phenomenon involved in oncogenic transformation and tumor progression, is associated with the insufficiency of the multicomponent DNA repair complex, in particular, the nucleotide mismatch repair (MMR) system. The MMR defect manifests itself as abnormalities in DNA microsatellite repeats, or microsatellite instability (MSI). In the studies of colorectal cancer, the role of MSI in prognostication of the disease, and defining the choice of specific therapy with immune checkpoint inhibitors has been proven.

However, in lymphatic system tumors, the significance of this phenomenon is poorly understood. Determination of genetic instability in the onset of follicular lymphoma, a disease characterized by a heterogeneous course, may have prognostic value.

Objective: to determine the genetic instability at the onset of follicular lymphoma.

Materials and methods. Here we report an analysis of 24 microsatellite repeats and amelogenin loci in tumor cells of 46 follicular lymphoma patients.

Results. In the studied cohort, lesions in microsatellite repeats were presented by MSI in 9 cases (19.6 %) and the loss of heterozygosity (LOH) in 19 cases (41.3 %). Most frequent lesions were found for the SE33 marker located at the q14 locus of chromosome 6. A significant association was shown between MSI and the double-hit follicular lymphoma group with rearrangements of the MYC and BCL₂/BCL₆ genes.

Conclusion. Thus, our data indicate that the MSI phenomenon might be involved in the pathogenesis of the lymphatic tumors and particularly follicular lymphoma. However further studies on the expanded cohorts of patients are required to define the possible prognostic value of MSI in lymphatic tumors.

The objective of the study a detailed, systematic review of the world literature data, which includes all aspects of recommendations for vaccination against SARS-COV‑2 in cancer patients.

Materials and methods. Information search was carried out in PubMed, MedLine, Scopus, Web of Science, RSCI.

The work included data from literature and information sources that were published before February 2021.

Results. The data of retrospective and prospective clinical studies are analyzed. This paper reflects considerations and recommendations for the vaccination of cancer patients by Russian and foreign specialists in the context of COVID‑19 pandemic. The review presents current recommendations for vaccination against SARS-COV‑2 in patients with solid tumors, hematological malignancies, recipients of hematopoietic stem cells and cell therapy.

Conclusion. To date, groups at increased risk of infection with the new coronavirus have been identified. These groups include patients with cancer. The presence of tumor does not allow a delay in start of therapy, and requires careful monitoring and observation. In this regard, despite the pandemic, the treatment of cancer patients must be continued regardless of the circumstances. Cancer patients should not be deprived of the opportunity to be vaccinated against SARS-COV‑2. Every patient should be decided individually. At the moment, there are no officially approved recommendations for vaccination against SARS-COV‑2 for cancer patients. Before the creation and approval of final recommendations for cancer patients, it is necessary to focus on compliance with sanitary and anti-epidemic measures and the prevention of COVID‑19 infection. The global cancer community continues to actively develop recommendations for the optimal vaccination against SARS-COV‑2 in cancer patients.

The most relevant ones are outlined in this article.

The article presents the case of successful extracorporeal membrane oxygenation in severe acute respiratory distress syndrome in a child with malignant brain tumor. This method can be used in children with oncological diseases, taking into account the underlying disease and risk factors, considering strict implementation of the recommendations on concomitant therapy, laboratory control and monitoring.

Infectious complications remain one of the most significant problem associated with anticancer therapy in oncological patients. Cytotoxic, radiation and antibacterial therapy induce dysbiosis and gastrointestinal mucosal barrier injury. These changes lead to the mucositis, thereby increasing the risk of endogenous microflora translocation with following probable development of severe infectious and inflammatory diseases. In addition, current evidence suggests that there is a relationship between gut microbiome disturbances and post-transplant graft versus host disease development. The article presents the existing paradigms of determining the role of gastrointestinal tract functional condition in cancer patients in order to optimize prevention and antimicrobial treatment approaches.

The objective of the study was to conduct a comparative pharmacoeconomic analysis of the treatment with posaconazole in a tablet form for the prevention of invasive fungal infections in patients aged 13 years and older with prolonged neutropenia and hematopoietic stem cell transplant recipients.

Study design: pharmacoeconomic study, cost–effectiveness analysis; budget impact analysis; sensitivity analysis to changes in the initial parameters of the model.

Results and conclusion. A literature review has shown that the use of the compared drugs for the prevention of invasive fungal infections is effective, with posaconazole being the most effective. Based on pharmacokinetic studies data, we can state the equivalence of the action of various drug forms of posaconazole. A cost analysis of drugs showed that the lowest total costs were for the prevention of invasive fungal infections in patients with acute myeloid leukemia with posaconazole tablets (197,149.37 rub.) and posaconazole suspension (215,911.53 rub.). The lowest cost for the prevention of invasive fungal infections in patients with hematopoietic stem cell transplant was shown by posaconazole in tablets (505,070.37 rub.) and posaconazole in suspension (616,652.01 rub.). Budget impact analysis in acute myeloid leukemia patients showed that with a possible cohort size of 2288 people an increase in the share of posaconazole in tablets from 5 to 15 %, in suspension from 20 to 35 % and with a decrease in the share of voriconazole from 25 to 15 %, and the share of fluconazole from 50 to 35 % in public procurement will reduce budget costs by 30,441,219.72 rub., and in patients with hematopoietic stem cell transplant ‒ by 11,219,243.54 rub. (per 100 patients).