Background. This article presents a thorough medical and legal examination of the principle of "discretion" in the surgical management of malignancies. The significance of this study arises from the mandatory implementation of clinical guidelines effective January 1, 2022, in accordance with Article 37 of Federal Law No. 323-ФЗ. This legislation has notably restricted the scope for individualized medical decision-making. At the same time, the complete algorithmization of surgical oncology remains fundamentally impossible due to the unique features of each clinical case. The authors interpret medical discretion as a specific form of administrative discretion – a legally conferred right enabling physicians to make informed and independent decisions based on clinical circumstances, evidence-based data, and the overarching principle of safeguarding the patient's health. Aim. To provide a comprehensive medical and legal analysis of the "discretion" principle within the surgical phase of cancer treatment, including examining its legal boundaries, its relationship with clinical guidelines, and the notion of informed voluntary consent, as well as an assessment of relevant law enforcement practices. Materials and methods. The study used system analysis, formal legal analysis, comparative law, and content analysis of judicial rulings. A total of 87 judicial decisions about civil cases from 2018 to 2025, relevant regulatory frameworks, and clinical guidelines issued by the Ministry of Health of Russia, the Association of Oncologists of Russia, the Russian Society of Clinical Oncology (RUSSCO), as well as NCCN and ESMO guidelines, along with the 8th edition of the TNM classification of malignant tumors, were reviewed. Results. The findings indicate that discrepancies in clinical and pathomorphological staging, which may reach up to 23.9% in colorectal cancer, render intraoperative approach adjustments a necessary practice. Analysis of specific court cases revealed that the legitimacy of extending the surgical intervention is evaluated not by the outcome but by the appropriateness of the surgeon's actions at the time they were performed, based on the intrinsic connection between surgical practices and pathological morphology, thereby facilitating a clear distinction in responsibility between surgery and pathology teams. Particular importance is attached to informed voluntary consent; it is the substance and completeness of this consent – rather than the mere availability of the document itself – that serves as the decisive mechanism for risk allocation. Conclusion. The authors establish criteria for the legality of extending the surgical intervention and advocate for enhancements to clinical guidelines, the format of informed voluntary consent, surgical protocols, the introduction of a standard for the "reasonable surgeon," and the legislative endorsement of the concept of "reasonable medical risk."

On May 15, 2026, Moscow hosted the 37th Lymphorum Interactive Expert Forum, which focused on contemporary approaches to the diagnosis and treatment of lymphoproliferative diseases. The interactive format of this event included the analysis of challenging clinical cases in collaboration with clinicians, pathomorphologists, and clinical experts. This review presents an analysis of 10 clinical cases presented during the forum sessions, along with insights from pertinent studies that underpin current pharmacological strategies for patients with lymphoproliferative diseases. Such scientific events underscore the importance of collaborative efforts among specialists from diverse fields to enhance treatment outcomes and improve the quality of life for patients with oncohematological diseases.

ObjectiveThe objective of the study was to compare the results of quality assessment of Russian-produced clinical practice guidelines on the use of direct oral anticoagulants in the treatment and prophylaxis of coronavirus disease 2019 using the RIGHT checklist and AGREE II instrument.MethodsWe assessed six relevant clinical practice guidelines published between 2020 and 2023 in Russian databases using the RIGHT checklist. We compared the results of using the RIGHT tool with the results obtained using the AGREE II instrument.ResultsAll six clinical guidelines received high scores in the sections "Basic information" (range: 56.2%-70.8%) and "Background" (48.4%-74.0%). The lowest results were obtained in the sections on RIGHT: "Review and quality assurance" (0%-4.2%) and "Funding and declaration management of interests" (14.6%-19.8%).ConclusionThe RIGHT checklist was proven applicable and usable for evaluating Russian-produced clinical practice guidelines. The use of RIGHT reporting tool enriched the depth and breadth of quality assessment to identify more areas that are problematic and to critically appraise details of the problems. More efforts are needed to further improve Russian clinical practice guidelines and their implementation into clinical practice to ensure better patient care and rational use of direct oral anticoagulants.

Aim. To evaluate the efficacy and safety of immune checkpoint inhibitors in patients with metastatic renal cell carcinoma (RCC) in the Russian patient population. Materials and methods. This retrospective study included 231 patients (157 males and 74 females) aged 44 to 86 years (median 64.56±8.09) who underwent examination and treatment at Moscow City Hospital named after S.S. Yudin and Moscow Center for Rehabilitation Treatment. Results. The median follow-up was 16.6 months (13.38-18.61). The effectiveness of therapy was evaluated in all patients included in the study. Objective response (complete regression + partial regression) was achieved in 45 (19.5%) patients. Disease control (objective response + stabilization) was reported in 186 (80.5%) subjects. Median of overall survival in patients with metastatic RCC was 15.62 months (95% confidence interval [CI] 12.89-17.75): in the 1st line group, 13.18 months (95% CI 11.21-17.75), and in the 2nd and subsequent lines group, 16.72 months (95% CI 13.41-20.19). Grade 1-2 immune-mediated adverse events were reported in 81.8% (n=189) of patients, of which 97 (78.9%) received 1st line immunotherapy and 92 (85.2%) received 2nd and subsequent lines. Conclusion. RCC immunotherapy in the Russian population is associated with high rates of objective response and disease control in the first line of treatment (19.5 and 80.5%, respectively). This treatment method is typically associated with a small number of grade 3-4 immune-mediated adverse events (3.03% according to our data), which indicates an acceptable safety profile and is comparable with the data from foreign studies.

Aim. To evaluate the survival rates in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in routine clinical practice in Russia and to analyze the impact of clinical and demographic factors on therapy selection and treatment outcomes. Materials and methods. An observational study of CLL/SLL treatment strategies has been conducted in 34 centers in Russia from 2021 to the present. Effectiveness was assessed based on survival rates, clinical characteristics, and therapeutic approaches. Statistical analysis included descriptive methods and Kaplan–Meier curves for survival outcomes. Cox proportional hazards models were used to assess the influence of various factors on progression-free survival (PFS). Results. As of the interim analysis (2021–2024), a total of 2,094 patients were included in the study. The majority of the cohort consisted of male patients (54.11%) aged ≥ 65 years (59.8%). Most patients (77.94%) had a favorable performance status of 0–1 according to the ECOG scale. Among molecular-genetic alterations, wild-type TP53 (86.43%) and IGHV (69.27%) were most commonly observed. According to the analysis of treatment data, the most frequently prescribed combinations were FCR (22.32%) and RB (18.67%). In later treatment lines, the proportion of targeted therapies increased. Overall survival among 1654 patients with known treatment start date remained high throughout 10 years of follow-up, and was 93.88% by year 10. Progression-free survival (PFS) was assessed for all patients receiving first-line therapy, including retrospective data. PFS was assessed separately for the second and subsequent lines by type of therapy. PFS among patients who received first-line therapy, regardless of the type of chemotherapy and the presence of TP53/IGHV mutation after 5 years was 76.93%. PFS in the targeted therapy group in patients who received the third, fourth and subsequent lines of therapy was significantly higher than in the immunochemotherapy group (p = 0.001 and 0.009 respectively). According to the Cox model, among patients who received first-line therapy, a significant association of a reduced risk of progression with male gender was shown (HR 0.52, 95% CI 0.33–0.82; p 0.005). There was a trend towards an association of TP53 mutation with a high risk of progression (HR 2.02, 95% CI 0.91–4.51; p = 0.084), but statistical significance was not achieved. In patients who received the third, fourth and subsequent lines of therapy, targeted therapy was significantly associated with a lower risk of progression (HR 0.16, 95% CI 0.05–0.53; p = 0.002 and HR 0.27, 95% CI 0.10–0.75; p = 0.012, respectively). Conclusion. The interim analysis showed generally favorable PFS dynamics, but some subgroups of patients, e.g., those with TP53 mutation, demonstrated a less favorable prognosis. Targeted therapy was significantly associated with a lower risk of disease progression among patients receiving third, fourth, and subsequent lines of therapy. The obtained results confirm the data on the high efficiency of targeted therapy in the treatment of CLL/SLL, especially in patients with an aggressive course of the disease and unfavorable prognostic factors.

Background. Anti-PD-1 immunotherapy (IT) is the standard of care for patients with metastatic melanoma. However, in the real world, IT is effective only in a fraction of patients. The lack of valid prognostic factors for various immunotherapy agents warrants a comprehensive and advanced study of this topic. Aim. To improve the outcomes of the first-line therapy for disseminated melanoma based on identifying immunohistochemical predictors of IT efficacy. Materials and methods. Data from 130 patients who were treated with immune checkpoint inhibitors nivolumab or prolgolimab in the first-line therapy for disseminated melanoma between 2017 and 2024 were analyzed. Results. The expression of PD-L110 on tumor cells was found to be a predictor of effective therapy: in the nivolumab group, the 2-year disease-free survival (DFS) with PD-L1 level 10% was high at 79% (95% confidence interval – CI 61–100); the 1-year DFS was 89% (95% CI 78–100) compared to 17% (95% CI 3.2–88) with a lower level of PD-L1 expression (p0.0001). In the prolgolimab group, the 2-year DFS with PD-L110% was also high at 78% (p0.0001; CI 54–100), the 1-year DFS was 94% (95% CI 84–100) compared to 35% (95% CI 17–73) with a lower level of PD-L1 expression (p0.0001). A less severe course of the disease was observed in patients with both peritumoral and intratumoral locations versus those with only peritumoral locations of the immune infiltrate. The study of the presence and form of lymphoid infiltration of the tumor showed the following direct relationship: in the nivolumab group, the 2-year DFS was 94% (95% CI 83–100) compared to 8.3% (95% CI 1.3–54), in the prolgolimab group, the 1-year DFS was 82% (95% CI 68–100) compared to 15% (95% CI 2.6–86); p0.0001. It was found that the predominance of CD8+ over CD4+ is associated with better results of IT: in the nivolumab group, the 2-year DFS was 87% (95% CI 74–100) compared to 19% (95% CI 4–91) in the absence of CD8+ predominance over CD4+; in the prolgolimab group, the 2-year DFS was 73% (95% CI 51–100) in patients with CD8+ predominance over CD4+ (p=0.0001). In patients without CD8 predominance over CD4, 2-year DFS was not achieved. The one-year DFS was 85% (95% CI 70–100) and 25% (95% CI 8.4–76), respectively; p=0.0001. Conclusion. The results of the study suggest that immunohistochemical characteristics such as a PD-L1 expression level 10%, the simultaneous presence of peri- and intratumoral lymphoid infiltration of the tumor, the ratio of the intensity of lymphoid infiltration with tumor-infiltrating lymphocytes (TILs), and the predominance of CD8+ over CD4+ can be considered predictors of IT efficacy with nivolumab and prolgolimab.

Background. Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of hematological malignancies, the vast majority of which are B-cell tumors. The most common variant of NHL is diffuse large B-cell lymphoma (DLBCL), characterized by an aggressive course, which accounts for 30–40% of all NHL. The second most common is follicular lymphoma (FL), traditionally classified as an indolent variant accounting for up to 25% of all NHL. Current therapies for these lymphoproliferative disorders which includes innovative drugs in the 1st line of therapy (LT) have demonstrated high efficacy. However, some patients develop a relapse or a refractory disease. Despite recent significant progress in the development and implementation of innovative targeted drugs, in most cases, it is not possible to achieve persistent long-term remissions after disease relapse, which leaves patients with an unmet need for effective and well-tolerated treatment options. Aim. To obtain objective data on the incidence, clinical course, and effectiveness of therapy for the most common variants of NHL in real-world practice in Russia. Materials and methods. From February to March 2023, 130 hematologists and oncologists from 30 regions of Russia were surveyed to update the data on DLBCL and FL. Results. Over the past 12 months, 5,689 patients with NHL were observed, of which 56% had DLBCL; 62% of them received the 1st LT, 22% received the 2nd LT, 10% received the 3rd LT, and only a few reached later lines. Analysis of the administered treatment options in the 2nd and 3rd LTs shows that there is no standard of care for this population, and the effectiveness of the regimens used in real-world Russian practice is extremely low. FL accounted for 23% of all 5,689 patients with NHL, of which 56% were newly diagnosed and 44% received treatment for relapse. The majority of patients with FL who received ≥3 LTs had an inferior prognosis and rapid disease progression: the median time from diagnosis to the beginning of the 3rd LT was only 26.4 months. The analysis of treatment options for patients with relapsed FL indicates a lack of standard and effective therapies. Conclusion. Relapsed and refractory DLBCL and FL represent a complex clinical situation where the main goal of treatment is disease control due to the impossibility of achieving stable remissions with existing treatment options. Clinicians with great hope are looking to the emergence of new classes of drugs that will be able to improve the prognosis for this complex population.

Background. According to the literature, the role of combined positron-emission and X-ray computed tomography (PET/CT) in diagnosing primary adrenal tumors (AT) remains limited due to both the frequency of these neoplasms and the availability of the method. Various research is required to assess the diagnostic resources of PET/CT with 18-fluorodeoxyglucose (18F-FDG). Aim. To evaluate the clinical role of PET/CT with 18F-FDG in the diagnosis of primary adrenal malignancies (PAM). Materials and methods. The study included 9 patients, 5 males and 4 females aged 44–76, with a median age of 59.3 years, with a morphologically confirmed diagnosis of the PAM. All patients underwent PET/CT with 18F-FDG. Visual and quantitative analysis of the obtained images was performed, including determination of the standardized maximum accumulation coefficient (SUVmax) in the tumor, liver, and spleen, the ratio of SUVmax of the primary tumor to SUVmax in the liver and spleen. Tumors were more often localized on the right (5/55.6%), and one case was bilateral. The maximum size of the adrenal mass averaged 6.8 cm (3.2–11.2) and the minimum size was 6.0 cm (2.3–9.0). The median SUVmax in AT was 10.0 (3.54–22.29), while in liver and spleen, it was 3.16 and 2.34, respectively, and the ratio of tumor SUVmax to liver and spleen SUVmax was 3.33 and 4.48, respectively. Conclusion. Hybrid PET/CT with 18F-FDG is a medical imaging method with a high diagnostic accuracy of PAM. PET/CT showed significant 18F-FDG tumor uptake, with a median SUVmax of 10.0 and a ratio of tumor SUVmax to liver and spleen SUVmax of 3.33 and 4.48, respectively. PET/CT with 18F-FDG may be a method of choice for diagnosing primary ATs.

Background. Small cell lung cancer (SCLC), predominantly due to smoking, is a highly differentiated, rapidly growing epithelial cell carcinoma of high malignancy originating from bronchial neuroendocrine cells. Almost 70% of SCLC patients have metastases at the time of diagnosis, which requires the use of drug therapies, including immunotherapy. Aim. To evaluate the efficacy and safety of immune checkpoint inhibitors in patients with small cell lung cancer. Materials and methods. One hundred and twenty one patients (90 men and 31 women) aged 44 to 84 years were included in the retrospective multicentre non-randomised study. The majority (90.9%) of patients were treated in the 1st line of therapy. IT were administered in the 2nd line and subsequent lines of treatment in 9.1% of patients. Weakened (ECOG 2–3) state at the time of treatment initiation was noted in 30 (24.8%) patients. Results. Progression-free survival in patients with SCLC receiving 1st-line treatment was 5.82 (95% CI 3.92–7.72) months, and 2nd-line and beyond was 6.21 (95% CI 0.76–11.66) months. Survival in patients with small-cell lung cancer receiving 1st-line IT was 8.0 (95% CI 6.18–9.81) months, and 2nd-line or longer was 11.3 months (95% CI 4.31–18.29) months (p=0.108). Objective response was achieved in 43 (35.5%) patients, of whom 38 (34.5%) were on first-line IT and 5 (45.5%) patients were on 2nd or more. iAEs grade 3–4 was observed in only 18 (14.9%) patients. Conclusion. Immunotherapy for SCLC allows achieving high rates of objective response and disease control. This method of treatment is characterized by insignificant number of grade 3–4 immune-mediated adverse events, which indicates an acceptable safety profile.

Introduction. Anti-PD-1 immunotherapy (IT) is becoming the standard treatment for patients with metastatic melanoma. However, immune checkpoint inhibitors are only effective in a fraction of patients, and studies examining biological markers and their correlation with clinical efficacy are insufficient to draw unambiguous conclusions. Aim. To improve the outcomes of the first-line therapy for disseminated melanoma based on identifying clinical and immunohistochemical predictors of IT efficacy. Materials and methods. Data from 130 patients who were treated with immune checkpoint inhibitors (nivolumab or prolgolimab) in the first-line therapy for disseminated melanoma between 2017 and 2024 were analyzed. Results. Improvement was observed in 24 patients (18.4%): complete response in 18 patients (13.8%), partial response in 6 (4.6%), and stabilization in 71 (54.6%) patients. Progression was reported in 31 (24%) patients. Death occurred in 4 (3%) cases during IT with prolgolimab due to disease progression. The two-year disease-free survival (DFS) during IT was 53% (95% confidence interval [CI] 42–67), p=0.63; the median 2-year overall survival was not reached. In the immunohistochemical study, 47 (63.5%) patients had a predominance of tumor infiltration with CD8 lymphocytes over CD4, regardless of the IT type: 2-year DFS 82% (95% CI 70–96) vs 13% (95% CI 2.7–64) in the absence of CD8 predominance over CD4, p=0.0001; the median DFS was not reached in patients with the predominance of CD8 lymphocytes tumor infiltration over CD4 compared to the other group – 7.6 months in the absence of this feature (95% CI 5.8–0), p=0.001. The peritumoral location of the immune lymphoid infiltrate was observed in all 74 (100%) patients, and the intratumoral location was less common (52 patients, 70%). In the presence of both periand intratumoral location of the immune infiltrate, the 2-year DFS was 83% (95% CI 70–98) compared to the group of patients in whom no intratumoral location was detected – 5.5% (95% CI 0.8–36), p0.0001. The expression of programmed cell death ligand 1 (PD-L1) level 10% was observed in 47 (63.5%) patients. With this level of PD-L1 expression, the one-year DFS was 91% (95% CI 83–100) compared to 29% (95% CI 15–57) with a lower level of PD-L1 expression, p0.0001; the median DFS is reached, and in the group 2, DFS was only 6.6 months. In the case of PD-L110%, the 2-year DFS was high at 78% (95% CI 63–100), p0.0001. Conclusion. Based on the study's results, it can be assumed that immunohistochemical characteristics such as a PD-L1 expression level 10%, the simultaneous presence of periand intratumoral lymphoid tumor infiltration, and the predominance of CD8 over CD4 can be considered predictors of IT efficacy with nivolumab and prolgolimab.

Abstract Objectives Radioactive iodine therapy is considered for patients with certain clinicopathological factors that predict a significant risk of recurrence, distant metastases of thyroid cancer or disease-specific mortality. The aim of the study was to investigate the association between polymorphisms of genes, products of which are involved in the processes of DNA damage response and autophagy, and the adverse reactions of radioiodine therapy in thyroid cancer patients. Methods The study included 181 patients (37 men, 144 women; median age 56 [41; 66.3] years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. NFKB1, ATM, ATG16L2, ATG10, TGFB1, and TNF polymorphisms were determined by allele-specific realtime-PCR. Results The frequency of adverse reactions was the following: gastrointestinal symptoms – 57.9 %, local symptoms – 65.8 %, cerebral symptoms – 46.8 %, fatigue – 54.4 %; signs of sialoadenitis six months after radioiodine therapy – 25.2 %. TT genotype carriers of ATG10 rs1864183 had higher frequency of gastrointestinal symptoms (vs. CC+CT), the CC genotype carriers of ATG10 rs10514231 had significantly more frequent cerebral symptoms (vs. CT+TT), as well as AA genotype carriers of TGFB1 rs1800469 (vs. AG+GG). CC genotype of ATG10 rs10514231 increased the incidence of radioiodine-induced fatigue, whereas GA genotype of the ATM rs11212570 had a protective role against fatigue. TGFB1 rs1800469 was associated with signs of sialoadenitis six months after radioiodine therapy. Conclusions Genetic factors may contribute to the occurrence of adverse reactions of radioiodine therapy in thyroid cancer patients.

Non-Hodgkin lymphomas are a heterogeneous group of hematological malignancies, the vast majority of which are B-cell tumors. Standard immunochemotherapy with anti-CD20 monoclonal antibodies is effective as the first-line therapy in treating these lymphoproliferative diseases. However, many patients develop a relapse or refractory disease. Recent therapeutic advances with new targeted agents and cell-based therapies have improved treatment outcomes. However, most of the new strategies cannot cure the disease or achieve long-term remissions, leaving a part of patients with an unmet need for effective and well-tolerated treatment options. One of the most promising therapeutic options is bispecific antibodies, which are expected to provide an unprecedentedly high level of deep responses with an improved safety profile. The available data open up prospects for extrapolating these results to the overall survival of patients.

Background. For a long time, interest in the HLA peptide complex is unabated, the clinical significance of which in cancer is still the subject of intense debate. Through the presentation of HLA antigens, tumor cells become available for recognition and destruction by effector cells of the immune system. A detailed analysis of the expression status of HLA molecules by breast cancer cells is of both scientific and important practical value. It can provide additional information about the immune system to determine a further strategy for treating breast cancer. Aim. To evaluate the frequency of expression of HLA-I and class II molecules by breast cancer cells and to determine its relationship with the morphological and clinical characteristics of the tumor. Materials and methods. This study included 82 patients with breast cancer who received treatment at the Blokhin National Medical Research Center of Oncology. Immunophenotyping of the primary tumor was performed by the immunohistochemical method (immunofluorescent staining) on cryostat sections. The reaction was evaluated using a ZEISS luminescent microscope (AXIOSKOP, Germany). The frequency of expression of HLA-I and class II molecules was studied depending on the clinical and morphological characteristics of breast cancer. Results. It was found that the frequency of expression of HLA I and II class molecules by breast cancer cells differed. HLA class I antigens are preserved in almost half of the cases 54.5%, while HLA class II antigens are preserved in 22.0%. Associations of molecules of the major histocompatibility complex with clinical and morphological signs of breast cancer were revealed. The frequency of HLA-DR negative cases increases in the stage advanсed (p=0.029). The frequency of monomorphic expression of HLA class II with T1 tumor was 50% versus 0% at T4 tumor (p=0.032). Estrogen receptor-negative tumors in most cases did not express HLA-II class (85.2% vs 64%; p=0.034). No connection with other clinical and morphological features of the tumor has been established. Conclusion. In most cases of breast cancer, the expression of HLA class II molecules is lost, while the expression of HLA class I is preserved in half of the cases. Monomorphic expression of HLA class II is characteristic of the early stage of breast cancer development and predominantly of receptor-positive tumors.

In 2022, the 100th anniversary of the birth of Professor Yu.I. Lorie was celebrated. Yuri Ivanovich Lorie is a talented Russian internal medicine specialist and hematologist, a wonderful teacher, and a person of great personal charm. Yu.I. Lorie is the founder of a new direction of hematology in Russia – oncohematology – and the establisher of a school based on deep knowledge and understanding of the oncological principles of hematological malignancies. Yuri Ivanovich Lorie lived a short (only 54 years) but bright life, utterly devoted to Russian medicine. He left a great legacy – a modern, rapidly developing direction in Russian medicine and a school of students who successfully continued the work he started. Looking back at the scientific and practical activities of Yu.I. Lorie and those emotional scientific debates that his colleagues and students remember, it becomes clear how many modern trends in the understanding of oncogenesis, diagnosis and treatment of hematological malignancies this legendary scientist established.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous orphan lymphoproliferative disease with an aggressive course, which accounts for 30–40% of all non-Hodgkin lymphomas. Approximately 3,000 new cases of DLBCL are diagnosed annually in Russia. The trend towards a steady increase in DLBCL incidence worldwide and the rapidly changing treatment landscape with the introduction of innovative options require the updating of epidemiological data. Despite a deeper understanding of the lymphomagenesis and molecular heterogeneity of DLBCL, the R-CHOP regimen remains the first-line standard of care for the vast majority (74%) of patients in Russia and worldwide. The effectiveness of this approach varies greatly and depends on several clinical, biological, and genetic factors. Currently, the most effective and simple prognostic model is the International Prognostic Index (IPI), according to which approximately 20% of patients are at intermediate/high risk of early progression (IPI3-5) and require therapy modification. After the first-line standard immunochemotherapy, 60–70% of DLBCL patients achieve long-term remission with the potential for cure. However, the occurrence of relapse or refractory disease in the remaining 40% of patients is associated with an abysmal prognosis with a median overall survival of about 6 months, which tends to decrease with each subsequent line, warranting an urgent need for new innovative treatments for patients with relapsed DLBCL.

Immunodeficiency occurs when one or more immune system components do not function properly, resulting in the body's inability to resist mostly infectious agents. Most cases of immunodeficiency in adults are acquired (secondary), but congenital immunodeficiencies are not uncommon. Primary immunodeficiencies are a heterogeneous group of innate immune errors that result in various clinical and laboratory manifestations. In contrast, secondary immunodeficiencies involve an acquired decrease in immune cell count and/or impairment of their function, commonly associated with an antibody level decrease. Secondary immunodeficiency in patients with B-cell hematological malignancies is a common condition attributed to both hematological malignancy and secondary antitumor therapy-related causes. Paradoxically, immunodeficiency, initially attributed to secondary causes, may be due to a previously undiagnosed primary immunodeficiency. Early diagnosis of immunodeficiency and optimization of management strategies with a multidisciplinary approach are critical to providing the most effective specific treatments and reducing the incidence of infection-related complications and mortality. The article addresses clinical practice, recommendations, and problems of immunodeficiency diagnosis and the effectiveness of immunoglobulin replacement therapy illustrated by clinical cases.

Background. One of the main stages of the treatment of breast cancer (BC) is endocrine therapy with tamoxifen or aromatase inhibitors. Five years of adjuvant tamoxifen therapy reduces the risk of disease recurrence by 39%. Tamoxifen was approved by the U.S. Food and Drug Administration in 1977 as a treatment for ER-positive BC. However, sometime after the start of tamoxifen's wide use, reports have been published on its long-term adverse effects. Most common were hot flashes, gynecological symptoms (vaginal dryness, vaginal discharge), depression, forgetfulness, sleep changes, weight gain, and decreased libido. However, more serious adverse events such as venous thromboembolic disease and endometrial hyperplasia or cancer are the most clinically significant. The article presents the results of a retrospective population-based study on assessing hyperplastic processes of the endometrium (HPE) in patients with breast cancer during TAM therapy, conducted in 2017, approved by the Ethics Committee of the Scientific Research of the Russian Medical Academy of Continuing Professional Education. Aim. To identify clinical factors that may increase the risk of HPE during tamoxifen therapy in patients with a history of breast cancer living in the Moscow region. Materials and methods. We retrospectively reviewed 230 case histories of patients with breast cancer. Of these, 120 patients who received TAM therapy had the following HPE risk factors: average age, menopausal status, body mass index, and duration of TAM therapy. Results. It was found that patients with HPE taking TAM were older (p=0.017), more likely to be postmenopausal (p=0.035), overweight (p=0.023), and received TAM for a longer period (p=0.028) than patients without HPE. Conclusion. The data obtained indicate the need for continuous monitoring by gynecologists of patients with breast cancer taking tamoxifen, paying particular attention to women from high-risk groups, namely older postmenopausal women with high body mass index receiving TAM for more than 1.52 years.

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are common complications of CLL. The optimal treatment of steroid refractory AIHA/PRCA is not well established. We conducted a multicenter study of ibrutinib and rituximab in patients with relapsed/refractory to steroids AIHA/PRCA and underlying CLL. Protocol included induction (ibrutinib 420 mg/day and rituximab, 8 weekly and 4 monthly infusions) and maintenance phase with ibrutinib alone until progression or unacceptable toxicity. Fifty patients were recruited (44—warm AIHA, 2—cold AIHA, 4—PRCA). After the induction 34 patients (74%) have achieved complete response, 10 (21.7%) partial response. Median time to hemoglobin normalization was 85 days. With regards to CLL response 9 (19%) patients have achieved CR, 2 (4%) patients—stabilization and 39 (78%)—PR. The median follow-up was 37.56 months. In AIHA group 2 patients had a relapse. Among 4 patients with PRCA 1 patient did not respond, and 1 patient had a relapse after CR, 2 remained in CR. The most common adverse events were neutropenia (62%), infections (72%), gastrointestinal complications (54%). In conclusion ibrutinib in combination with rituximab is an active second-line treatment option for patients with relapsed or refractory AIHA/PRCA and underlying CLL.

Diffuse large B-cell lymphoma (DLBCL) is the most common variant of non-Hodgkin's lymphoma and accounts for about 1/3 of all non-Hodgkin's lymphomas in Western countries and about 40% of B-cell tumors worldwide. Correct diagnosis of clinically distinct subgroups of aggressive mature B-cell lymphomas is crucial for the choice of adequate treatment. Currently, the identification of DLBCL subtype depends on a combination of morphologic, immunophenotypic, and cytogenetic/molecular features. The classification covers the most common unspecified variant of DLBCL, also referred to as "not otherwise specified" (NOS), and a number of other rare forms. Over the past two decades, DLBCL NOS which accounts for more than 80% of all cases, has been the subject of a growing number of molecular studies that have identified prognostic factors that are being actively introduced into real-world clinical practice. Only the integration of morphological, immunohistochemical and molecular features of DLBCL will lead to the achievement of the long-term goal of curing the majority of patients with minimal or no toxic manifestations with the aid of personalized healthcare.

The authors reveal the conditions and factors of health care system development that have emerged to date, indicate their content, and note the role of legal regulation of health care. The influence of aggravation of the international situation is noted, and the resulting risk of national origin discrimination against Russian citizens is addressed. The risk of discrimination against Russian citizens in providing health care abroad is presented as a trend. In this respect, the authors suggest some organizational and human rights measures and directions of support and protection of the rights of Russian citizens.