Background. The use of molecular genetic profiling in clinical practice and the registration of immunotargeted agents have undoubtedly led to the development of a personalized approach in oncohematology, with diffuse large B-cell lymphoma (DLBCL) being no exception. Elderly patients represent a complex group of patients with DLBCL, which leads to difficulties in treatment due to their comorbidity.
Aim. To evaluate the efficacy, tolerability and safety of an individualized approach based on the mutational landscape in elderly patients with newly diagnosed DLBCL.
Materials and methods. The clinical study included 10 elderly patients with newly diagnosed DLBCL. The median age was 68 (65–78) years. Eight patients were classified as being at high risk of early progression according to the international prognostic index. The frequency of genotypes in the considered cohort of elderly patients: MCD – 1 (10 %), N1 – 3 (30 %), BN2 – 1 (10 %), EZB – 2 (20 %), NOS – 3 (30 %).
Results. Overall and complete metabolic response rates were 100 %. Clinically significant hematological toxicity depending on the number of cycles (n = 60): grade III–IV neutropenia in 5 cycles, grade III–IV thrombocytopenia in 2, grade III–IV anemia in 3. Non-hematological toxicity did not exceed grades I–II.
Conclusion. High efficacy and low toxicity profile of a personalized approach in elderly patients with newly diagnosed DLBCL were demonstrated. The obtained preliminary results indicate the possibility of continuing the developed clinical study of elderly patients with DLBCL.

Background. Despite tremendous progress in understanding tumor biology, the R-CHOP protocol remains the standard of care for diffuse large B-cell lymphoma (DLBCL). To date, six genetic variants of DLBCL have been identified, the most unfavorable of which when using standard therapy are N1, MCD and BN2, which dictates the need to optimize the treatment of these DLBCL subtypes.
Aim. To evaluate the efficacy and toxicity of Acala-R-CHOP regimen in induction therapy in patients with newly diagnosed DLBCL.
Materials and methods. The study included 15 patients who received Acala-R-CHOP program as part of the first-line therapy. This antitumor regimen was used for verified genotypes N1, MCD and BN2. The median age was 64 (38–78) years. The incidence of genetic variants in the considered cohort of patients: MCD – 13 % (n = 2), N1 – 74 % (n = 11), BN2 – 13 % (n = 2).
Results. Fifteen patients completed the therapy. The overall and complete metabolic response rates were 100 %. Toxicity was moderate, quite manageable and manifested mainly as myelosuppression.
Conclusion. The efficacy of Acala-R-CHOP therapy in patients with MCD, N1, and BN2 DLBCL genotypes is high with a low toxicity profile. However, longer follow-up periods are needed to assess the long-term results in this unfavorable group of patients.

Aim. To analyze the efficacy and safety of combining nivolumab with AVD chemotherapy (N-AVD) in patients with newly diagnosed classical Hodgkin’s lymphoma in real-world evidence studies.
Materials and methods. The retrospective single-center study included 26 patients (14 men, 12 women) with advanced disease stages (IIB with unfavorable prognostic factors according to GHSG (German Hodgkin Study Group) or III–IV according to the Ann Arbor classification). Patients received therapy at the Leningrad Regional Clinical Hospital from March 2023 to February 2025. The N-AVD regimen included nivolumab at a dose of 3 mg / kg (maximum 240 mg), doxorubicin 25 mg / m2, vinblastine 6 mg / m2, and dacarbazine 375 mg / m2 on days 1 and 15 every 28 days. Patients with stage IIB were planned to receive 4 cycles of N-AVD, in case of stages III–IV – 6. Some patients received consolidating proton therapy – 6 (24 %) or 3D conformal radiation therapy – 6 (24 %). The primary endpoint of the study was progression-free survival, and secondary endpoints were the complete remission rate, safety, event-free survival, and overall survival.
Results. The complete remission rate was 94 %. With a median follow-up of 11.9 months, 1‑year progression-free survival was 95.7 %, and overall survival – 100 %. The most common adverse events were grade 3–4 neutropenia (46.2 %) and febrile neutropenia (11.5 %). Immune-mediated complications represented by two cases of hypothyroidism and acute pericarditis in one patient.
Conclusion. Preliminary results of our study demonstrate the high efficiency of the N-AVD regimen and emphasize the importance of monitoring immune-mediated complications. The advisability of consolidation radiotherapy in patients with complete remission on anti-PD1 monoclonal antibody therapy requires further study. Our study confirms the prospects of using the N-AVD regimen in patients with newly diagnosed classical Hodgkin’s lymphoma, but longer follow-up and a larger sample are needed for conclusions.

Chronic lymphocytic leukemia is the most common type of leukemia in adults. Kidney damage can be diagnosed at the onset of the disease or during its progression, relapse. In most studies, kidney damage in this disease was verified by the results of biopsy. Studies of recent decades have identified a wide range of kidney lesions in chronic lymphocytic leukemia, including lymphoid infiltration of parenchyma, glomerular and tubular damage caused by a monoclonal protein (M-protein) produced by B cells, thrombotic microangiopathy, worsening of comorbid pathology, additional infection, paraneoplastic reactions, tumor lysis syndrome, and drug-induced toxic kidney injury with damage of glomeruli, tubules, or renal vessels.
In this article, we consider various forms of kidney disease associated with chronic lymphocytic leukemia.

Idiopathic hypereosinophilic syndrome is characterized by a persistent increase in serum eosinophil counts >1.5 × 109 / L for 4 weeks and the absence of any clinical, laboratory and instrumental data suggesting the etiology of this phenomenon. It is not always possible to confirm the reactive nature of eosinophilia or identify clonal disease. The article presents a clinical case of differential diagnostic search for the cause of hypereosinophilia in a patient.

Background. The c-MAF oncogene, located in the 16q23.2 region, encodes the protein of the same name, a transcription factor whose role continues to be studied. Given the activating effect of the c-MAF transcription factor in enhancing the interaction between the tumor cell and the bone marrow stroma, we hypothesized that c-MAF protein expression would be more frequently detected in multiple myeloma (MM) patients without plasmacytomas.
Aim. To analyze the c-MAF protein expression pattern in bone marrow trephine biopsy specimens of patients with newly diagnosed MM with and without plasmacytomas.
Materials and methods. The retrospective single-center study included 31 patients (7 men and 24 women) with newly diagnosed MM aged 29 to 78 years (median – 55 years). The first cohort of patients included 12 patients with t(14;16), the second cohort – 19 patients without this translocation. In 21 patients, plasmacytomas were not detected at the disease onset, in 10 patients, bone or extramedullary plasmacytomas were detected. Low-dose body computed tomography was used to detect bone lesions. The diagnosis was established in accordance with the International Myeloma Working Group 2014 criteria. Positive immunomagnetic selection of CD138+ bone marrow cells was performed using a monoclonal antibody to CD138 (Miltenyi Biotec, Germany) according to the manufacturer’s protocol. Fluorescent hybridization in situ of CD138+ cells was performed using DNA probes to detect translocations 14q32 / IgH, 8q24 / MYC, deletions 17p13 / TP53, 13q14, 1p32, amplification of 1q21 (amp1q21) and multiple trisomies (MetaSystems, Germany). High-risk cytogenetic aberrations included t(14;16), t(4;14), del17p13, amp1q21. Immunohistochemical examination of bone marrow trephine biopsy specimens using c-MAF antibody was performed in all patients. A heterogeneous or monomorphic nuclear reaction in more than 10 % of the tumor plasma cells was considered as positive c-MAF protein expression.
Results. Cytogenetic examination of CD138+ bone marrow cells revealed high-risk aberrations in 24 patients, and standard risk cytogenetics was diagnosed in seven patients. c-MAF protein expression was detected in 29 % (6 of 21) of patients without plasmacytomas and in 70 % (7 of 10) of patients with plasmacytomas. c-MAF protein expression was strongly correlated with t(14;16) presence. In cases where it was absent, c-MAF protein expression in bone marrow was not observed, with the exception of one case. Thus, c-MAF protein expression in bone marrow was noted in 13 patients – twelve with t(14;16) and one patient with double hit myeloma (del17p13 and t(4;14)). No relationship was found between c-MAF protein expression and the presence / absence of plasmacytomas. In the presence of t(14;16), an atypical distribution of patients by paraprotein type was noted (immunoglobulins G, A, BJ myeloma occurred with the same frequency – 33.3 %). In MM with t(14;16), a tendency to more frequent detection of plasma cells in the peripheral blood was found (29 %); a quarter of patients had kidney damage. Plasmacytomas were detected in 50 % of patients with t(14;16), and in 25 % of them – extramedullary. Most patients with t(14;16) had stage III according to International Staging System (82 %).
Conclusion. The expression of c-MAF protein strongly correlated with t(14;16) presence, however, no correlation with the presence / absence of plasmacytomas could be found. MM with t(14;16) is characterized by an aggressive phenotype. In the presence of t(14;16), there is a tendency towards a high frequency of kidney damage, detection of extramedullary plasmacytomas and plasma cells in the peripheral blood, and diagnosis at advanced stages of the disease.

Background. Current protocols for pediatric acute lymphoblastic leukemia (ALL) are multicomponent, risk-adapted regimens in which high-dose (1–5 g / m2) methotrexate (MTX) is central. This drug has led to high long-term survival rates in children with ALL. Predicting the efficacy of the treatment given to further increase survival with minimization of toxic complications determines the relevance of pharmacogenetic studies to identify predictive biomarkers, implementing the personalized approach, which is essential for the development of modern practical medicine.
Aim. To identify predictors of ALL therapy outcomes using pharmacogenetic biomarkers and clinical data.
Materials and methods. A prospective analysis of pediatric ALL treatment outcomes was performed in a single-center observational (cohort) study. The analysis included 124 ALL patients who were treated according to the modern BFM (Berlin–Frankfurt–Munster) protocols with high-dose MTX. Treatment outcomes were compared with genetic polymorphisms of the ABCB1 gene, which is responsible for drug clearance (including MTX). Real-time polymerase chain reaction was used to study ABCB1 gene polymorphisms in peripheral blood. Statistical analysis of the influence of pharmacogenetic biomarkers was performed using SPSS Statistics 26.0 program (USA). To construct prognostic models, we used the method of logistic function construction by binary logistic regression with stepwise selection of factors and, if necessary, additional construction of ROC-curves with subsequent ROC-analysis. Differences were considered significant at p <0.05; at p ≥0.05, differences were considered unlikely and not statistically significant.
Results. According to the conducted complex analysis of high-dose MTX therapy efficacy and safety, 3 reliable (p <0.001) prognostic models with high sensitivity, specificity, and efficiency (>70 %) were developed, demonstrating interrelations of clinical and genetic factors influencing adverse outcomes of MTX therapy in children with ALL, which confirms the necessity of pharmacogenetic testing implementation in real clinical practice. Conclusion. Determination of polymorphisms of genes involved in transport and metabolism of cytostatic drugs should be introduced into clinical practice in order to further increase patient survival rates while reducing adverse effects of antitumor treatment.

Laboratory diagnostics of acute myeloid leukemia enables accurate risk stratification of patients into prognostic groups according to modern classifications and facilitates personalized treatment selection. However, relapses and refractory forms still occur within each prognostic group. Some cytogenetic and molecular aberrations cannot be detected using standard diagnostic methods. Modern advanced laboratory techniques may uncover the mechanisms of tumor refractoriness and identify novel targets for therapy, which could improve acute myeloid leukemia diagnostics and patient prognosis.

Background. Primary immune thrombocytopenia (ITP) is an immune-mediated disease characterized by platelet destruction and impaired thrombopoiesis with the development of varying severity hemorrhagic syndrome. The first line of therapy for ITP patients are glucocorticosteroids, which have limited efficacy and frequent complications. Factors of innate and adaptive immunity play a key role in ITP pathogenesis, the study of which is especially relevant for assessing the immunological reactivity of patients and substantiating new therapeutic approaches in real clinical practice.
Aim. To evaluate the characteristics of the subpopulation composition and functional activity of peripheral blood lymphocytes and monocytes in ITP patients and to identify possible immunological prognostic criteria for the disease course and resistance to glucocorticosteroid therapy.
Materials and methods. In 20 patients with newly diagnosed ITP and in 20 ITP patients with resistance to glucocorticosteroid therapy, the relative and absolute parameters of T-lymphocytes (CD3+), B-lymphocytes (CD19+), NK cells (CD3–CD16+CD56+), T-helper cells (CD3+CD4+), T-cytotoxic (CD3+CD8+) and NKT (CD3+CD16+CD56+) subpopulations of peripheral blood lymphocytes, as well as the expression of HLA-DR on lymphocytes and monocytes, CD25 on CD4+ T-lymphocytes and CD40 on B -lymphocytes were analyzed using flow cytometry. Thirty healthy individuals were examined as a control group.
Results. In patients with newly diagnosed ITP, a sharp decrease in the absolute number of B cells and T-helper lymphocytes in peripheral blood was observed, and pronounced activation of T-lymphocytes by HLA-DR expression and B-lymphocytes by costimulatory molecule CD40 expression was noted. In patients with glucocorticosteroids resistance, a significant decrease in the absolute number of peripheral blood T-helper lymphocytes, an increase in the content of activated CD3+HLA-DR+ lymphocytes were also detected, but the level of CD40+ B-lymphocytes was reduced compared to primary patients.
In patients of both groups, a significant (p <0.001) decrease in HLA-DR mean fluorescence intensity on peripheral blood monocytes was detected, which may indicate an insufficient ability of monocytes and macrophages to effectively antigen processing.
Conclusion. Patients with ITP have been found to have significant disturbances in the quantitative parameters of cellular adaptive immunity and the functional activity of peripheral blood lymphocytes and monocytes, which play an important role in the immunopathogenesis of the disease.

Allogeneic hematopoietic stem cell transplantation is a standard treatment option for a variety of hematological disorders. In recent years, there has been observed an increase in transplantation activity worldwide as well as in use of alternative donors. Despite introduction of antifungal prophylaxis, recipients of allogeneic hematopoietic stem cells still have a high risk of invasive fungal disease.
This review represents risk factors, frequency and structure of invasive fungal disease in this category of patients.

Background. Over the past few decades, the advancements in antitumor therapy, early diagnosis, and the development of stem cell transplantation techniques have led to a notable increase in the survival rates of oncohematological patients. Although effective chemotherapy has been shown to prolong lifespan, it can also contribute to toxic effects on gland function, which in women can result in impaired fertility and hormonal disorders related to sex hormone production. In order to mitigate or prevent the irreversible complications of antitumor therapy-induced gonadotoxicity, effective and comprehensive strategies that integrate a variety of options for preserving and restoring fertility should be implemented prior to, during, and following the chemotherapy or radiotherapy.
Aim. To test in clinical practice the principles of creating a management plan for oncohematological patients of reproductive age prior to starting special treatment.
Materials and methods. The study included 34 female patients of reproductive age with morphologically confirmed hematological diseases who underwent examination, treatment, and follow-up observation at the State Budgetary Healthcare Institution, City Clinical Hospital No. 52 of the Moscow Healthcare Department. All patients were referred for consultation with an obstetrician-gynecologist to evaluate their hormonal status and reproductive potential. Additionally, a multidisciplinary team, including a reproductive health specialist from REMEDI Institute of Reproductive Medicine LLC, assessed ovarian reserve and selected appropriate fertility preservation technique. A comprehensive review and discussion of all clinical cases was conducted within the framework of a multidisciplinary team, leading to a determination of the feasibility of fertility preservation.
Results. The material for fertility preservation was collected in 82 % of the patients. Hodgkin’s lymphoma was the most common malignancy (76 %). The methods employed for material collection included transvaginal follicle puncture following controlled ovarian stimulation in 89 % of cases and laparoscopy with ovarian resection / ovariectomy followed by cryopreservation of ovarian tissue in 11 % of cases. The fertility preservation methods included oocyte cryopreservation in 71 % of cases, embryo cryopreservation in 11 % of cases, ovarian tissue cryopreservation in 11 % of cases, and both oocyte and embryo cryopreservation in the remaining 7 % of cases. No complications were reported following assisted reproductive technology procedures.
Conclusion. Given the importance of reproductive potential and overall survival in the context of oncohematological diseases, reproductive specialists should prioritize selecting a fertility preservation method before initiating specialized treatment in all patients of reproductive age. The opportunity to procreate constitutes a pivotal component of quality of life for this particular patient population.

Background. High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a treatment option for hematological diseases, and can lead to severe neutropenia and an increased risk of infectious complications. The term “febrile neutropenia” combines all infectious complications, and fever may be the only sign of infection in this group of patients. Due to this, there is a need for additional diagnostic methods in clinical practice that can predict and diagnose infectious complications in patients after HDCT / auto-HSCT.
Aim. To evaluate the prognostic significance of inflammatory biomarkers (C-reactive protein, procalcitonin and presepsin) in the early detection of infectious complications, as well as the capabilities of these biomarkers in the diagnosis of bacteremia in patients with lymphomas and plasma cell neoplasms after HDCT / auto-HSCT.
Materials and methods. This prospective study included 139 patients with lymphomas and plasma cell neoplasms after HDCT / auto-HSCT. Infectious complications developed in the early post-transplant period in 99 (71.2 %) patients; 40 patients had no infectious complications, they formed the control group. The dynamics of C-reactive protein, procalcitonin and presepsin on day 1, 3 and 7 after stem cell infusion were assessed.
Results. The median time of fever onset was 5 (1–10) days after transplantation. On day 3, significant differences were observed between the group of infectious complications and the control group in all biomarkers: C-reactive protein, procalcitonin and presepsin were significantly higher in the group of patients with infectious complications. On day 3, procalcitonin demonstrated the highest specificity for infection: with values >0.11 ng / mL, the probability of infectious complications increased by 9 times, and the specificity of the test reached 88.9 %. In 77 patients with febrile neutropenia, microbiological cultures were negative; in 21 patients – bacteremia was detected. None of the biomarkers demonstrated their effectiveness in diagnosing bacteremia: the differences in biomarkers concentration in patients with bacteremia and with sterile cultures were insignificant.
Conclusion. Monitoring of C-reactive protein, procalcitonin and presepsin can facilitate early detection of infectious complications in patients after HDCT / auto-HSCT. The most significant day for assessing the biomarkers is day 3 after stem cell infusion. Procalcitonin monitoring is recommended for timely detection of patients with a high risk of severe infection and possible preventive antibacterial therapy.

Background. Treatment adherence is one of the key factors influencing the therapy outcome in patients with multiple myeloma complicated by pain syndrome.
Aim. To clarify the treatment adherence features in patients with multiple myeloma.
Materials and methods. The data of 61 patients with pain syndrome associated with bortezomib-induced polyneuropathy and oral mucositis were studied. Men – 17 (27.9 %), women – 44 (72.1 %). Median age – 52 (31–67) years. Assessment of pain syndrome and psychometric parameters of patients was performed in hospital before autologous hematopoietic stem cell transplantation (1st point), on the 8th (2nd point) and 100th (3rd point) days after transplantation. Validated algometric and psychometric methods were used.
Results. At each study point, patients with high adherence were grouped into 1st group, and patients with low adherence were grouped into 2nd group. At 1st point, statistically significant differences were noted between the groups in such indicators as quality of life / satisfaction and the degree of polyneuropathy. At the 2nd point, significant differences were found in the types of patient’s attitude toward illness: in the 1st group, adaptive types (harmonious, ergopathic) predominated, in the 2nd – maladaptive ones (anxious, neurasthenic, and sensitive). At 3rd point, a statistically significant difference was noted between the groups in the severity of mental disorders symptoms, the presence of which may be associated with decreased adherence to treatment, as well as the presence exclusively in the group with a low treatment adherence a maladaptive (egocentric) type of attitude toward illness.
Conclusion. Adherence to treatment in patients with multiple myeloma complicated by pain syndrome is a complex problem that requires a multidisciplinary team of specialists, which should include hematologists, algologists, and mental health specialists (psychiatrists, medical psychologists).