Background. In Russian clinical practice, there is no systematic information on patients with follicular lymphoma (FL) relapses after first-line therapy, and only isolated data are presented regarding the frequency of early and late relapses in the domestic population, first-line therapy regimens used in these patients, the dynamics of treatment response, timing of relapse, and second-line therapy regimens. A detailed analysis of a large cohort of patients with relapsed FL, including detailed clinical, laboratory, morphoimmunohistochemical, and molecular genetic characteristics, the treatments administered at onset and during relapse, as well as the identification of factors correlating with the risk of early progression, is of great scientific and practical interest. This is the focus of this study. Our results will be aimed at optimizing treatment and improving the prognosis of FL patients in Russia who have received second-line therapy. Aim. To describe changes in the therapeutic landscape of first-line FL therapy from 2001 to 2025 for patients receiving treatment at the National Medical Research Center for Hematology; to analyze the effectiveness of the therapeutic protocols used; to study cases of treatment resistance and identify significant factors influencing the prognosis of the disease; as well as to determine outcomes for patients with the first early relapse of nodal FL. Materials and methods. A retrospective and prospective study conducted from 2001 to 2025 at the National Medical Research Center of Hematology (Moscow) included 445 patients with newly diagnosed FL of cytological types 1–2 and 3A (World Health Organization, 2017). The median follow-up was 95 (1–251) months. All patients were treated according to the criteria of the Groupe d’Etude des Lymphomes Folliculaires. All patients included in the study were divided into two groups: those who received initial treatment between 2001 and 2022 (the historical control group; n = 374) and those who received initial treatment between 2022 and 2025 according to the new FL-2022 risk-based differentiated treatment protocol for patients with nodal FL (n = 71). Data for the two groups were analyzed separately. Results. With a median follow-up of 98 (1–251) months, the 2-year, 5-year, and 10-year overall survival of 374 patients from the historical control group (2001–2022) were 93, 90, and 85 %, respectively; 2-year, 5-year, and 10-year event-free survival were 82, 71, and 55 %, respectively. With high-dose chemotherapy, compared with standard regimens, the proportion of progressions / relapses was significantly lower (26 % versus 40 %; p = 0.01), but if events occurred, they were predominantly early (72 % versus 58 %; p = 0.2). According to the results of multivariate analysis, independent prognostic risk factors for disease progression within 24 months after the start of therapy (POD24) were identified: absence of BCL2 gene rearrangement (odds ratio 3.52 (1.89–6.55); p 0.0001) and 3A cytological type (odds ratio 3.8 (1.61–0.16); p = 0.0033). During second-line therapy in the first early relapse / progression after R-B (rituximab + bendamustine), R-CHOP (rituximab + cyclophosphamide + doxorubicin + vincristine + prednisolone) and autologous hematopoietic stem cell transplantation, complete remission was achieved in only 38 % of patients, and after R-DHAP it was not achieved in any case. With therapy according to the FL-2022 protocol (2022–2025), with a median follow-up of 23 months, 2-year overall survival was 100 %, 2-year event-free survival was 97 %. Second-line therapy was required in only 6 % of patients. Conclusion. The development of early relapse / progression has a critical impact on the survival prognosis of FL patients. The use of a differentiated treatment protocol for patients with nodal FL (FL-2022), based on clinical, morphological, immunohistochemical, and genetic prognostic factors, has significantly improved treatment outcomes and reduced the risk of POD24. When FL first relapses, there is no uniform treatment standard, and the regimens used vary greatly. Treatment outcomes in the first relapse remain modest, especially for the high-risk POD24 group, necessitating a change in the treatment paradigm for this patient group.

Nikolay Konstantinovich Goryaev (1875–1943) is recognized as an accomplished clinician and scientist who established fundamental principles in the field of hematology. His research focused on hematological disorders, in particular acute lymphoblastic leukemia, polycythemia, and splenopathies, as well as detailed investigations into the microanatomy and innervation of the spleen. He created the Goryaev chamber, a specialized device designed to facilitate the standardized counting of blood cells using a defined grid. Moreover, professor Goryaev founded a significant clinical school, mentoring numerous prominent specialists including V. I. Katerov, R. M. Akhrem-Akhremovich, I. I. Tsvetkov, P. S. Poptsova, S. I. Sherman, K. A. Dryagin, and others. Professor Goryaev was known for his attributes of integrity, diligence, empathy, and ethical conduct. He was consistently remembered with respect by his peers and former students. This article will explore professor Goryaev’s personal attributes, emphasizing their contribution to his professional achievements and his enduring influence within the medical community.

Background. Therapeutic options for patients with relapsed multiple myeloma (MM) after primary autologous hematopoietic stem cell transplantation (auto-HSCT) may include not only modern targeted therapies but also second auto-HSCT. Aim. To evaluate the efficacy of second auto-HSCT in the treatment of the first MM relapse, to identify prognostic factors influencing progression-free survival (PFS) and overall survival (OS), and to compare the early post-transplantation period following primary and second auto-HSCT. Materials and methods. This retrospective study included 23 patients (13 men and 10 women, median age 52 years) with MM who underwent primary auto-HSCT as consolidation after induction therapy and second auto-HSCT during the treatment of their first disease relapse. The effect of second auto-HSCT was assessed based on PFS and OS. In addition, the analysis of results also considered the PFS from primary auto-HSCT to the first relapse / disease progression. Results. The median PFS after second auto-HSCT was 26 months. Survival outcomes were significantly better in patients with a PFS of more than 18 months after primary auto-HSCT compared to those with a PFS of less than 18 months (median 32 months vs 9 months). Overall survival outcomes after second auto-HSCT were highly encouraging: the median OS was 75 months, with 3-year survival reaching 82 % and 6-year survival – 70 %. Second auto-HSCT was not associated with a higher risk of infectious complications in the early post-transplant period or a prolonged recovery of blood count parameters compared to primary auto-HSCT. Conclusion. Based on our results and literature data, second auto-HSCT can be safely performed in most MM patients who have relapsed after primary auto-HSCT.

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.

Waldenstrom’s macroglobulinemia (WM) is a subtype of lymphoplasmacytic lymphoma that combines lymphoplasmacytic lymphoma substrate in the bone marrow and monoclonal immunoglobulin M secretion in the blood. WM diagnosis is a complex process, which is due to both the heterogeneity of tumor populations and similarity to other B-cell lymphomas. The WM tumor cell clone has unique immunophenotypic characteristics and is represented by two aberrant populations from one tumor clone: clonal B-lymphocytes and plasma cells. Detection and characterization of these two aberrant populations seems possible only using multicolor flow cytometry. Bone marrow cell immunophenotyping by flow cytometry establishes the tumor cell immunophenotype, which plays a key role in the differential diagnosis of WM from other types of small cell lymphomas, as well as when other methods are uninformative.To assess the depth of therapy response, instrumental and laboratory methods are used, including positron emission tomography combined with computed tomography to monitor the size and spread of the tumor mass, immunochemical testing to measure the monoclonal immunoglobulin M secretion, molecular bone marrow research for the presence of MYD88 gene mutations, as well as bone marrow cell immunophenotyping by multicolor flow cytometry. Currently, it is especially important to study the dynamics of minimal residual disease in WM using the capabilities of multicolor flow cytometry.

Background. The most common mechanism of resistance to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML) is point mutations in the BCR::ABL1 gene. Of particular importance is the T315I mutation, which causes insensitivity of leukemia cells to all ATp-competitive TKIs: imatinib and 2nd generation TKIs. Asciminib is the first drug of the STAMp inhibitor class that specifically interacts with the myristoyl-binding active site of the bCR::AbL1 molecule. In a phase I clinical trial, asciminib at a dose of 200 mg twice daily showed efficacy in the treatment of chronic phase (Cp) CML patients with T315I mutation. There are no data on the efficacy of asciminib therapy in patients with T315I mutation and additional chromosomal abnormalities (ACA) or advanced disease. The Russian part of the managed access program (MAp) has accumulated its own experience of using asciminib in CML patients with T315I mutation, including those with ACA and history of progression to the acceleration phase / blast crisis.Aim. To analyze the 3-year results of asciminib therapy as part of MAp in CML patients with T315I mutation.Materials and methods. In the MAp program to asciminib between October 2019 and January 2022 were included 26 CML patients with T315I mutation who were ineffective or intolerant to ATp-competitive TKIs therapy. Asciminib was administered at a dose of 200 mg twice daily. The efficacy and tolerability of asciminib therapy were assessed in accordance with national clinical guidelines and the 2020 European LeukemiaNet guidelines.At the time of asciminib therapy initiation, 19 (73 %) patients had Cp. four (15 %) patients had a history of acceleration phase (n = 3) and blast crisis (n = 1). four (15 %) patients had ACA immediately before the start of asciminib therapy, including a patient with a history of blast crisis. To analyze the asciminib therapy results, patients with a history of progression and / or ACA were combined into one group: 2Cp / Cp ACA+ (n = 7). More than half of patients (54 %) had previously received ponatinib.Results. The median duration of asciminib therapy was 31.6 (3.3–50) months. Of the 26 patients, 25 (96 %) are alive, one patient in the 2Cp / Cp ACA+ group died from progression of CML to myeloid blast crisis. In the total group, 14 patients (54 %) continued asciminib therapy, 12 (46 %) – discontinued treatment: most patients due to treatment failure (n = 9 (75 %)). In 3 patients (25 %), the reason for treatment discontinuation was allogeneic hematopoietic stem cell transplantation (all three achieved a complete cytogenetic response with asciminib therapy). No patients discontinued treatment due to toxicity. No new mutations, including asciminib resistance mutations, were detected during therapy.Progression-free survival and survival without therapy discontinuation at 3 years of follow-up in the total group were 92 and 58 %, respectively. when analyzing the Cp and 2Cp / Cp ACA+ groups, progression-free survival at 3 years of asciminib therapy was comparable. There was a trend toward decreased survival without therapy discontinuation in 2Cp / Cp ACA+ group (28 %) versus Cp group (63 %) (p = 0.0856).The probability of achieving a complete cytogenetic response / molecular response MR2 in all patients with T315I mutation by the 3rd year of asciminib treatment was 59 %, in the Cp and 2Cp / Cp ACA+ groups – 47 and 80 %, respectively; no significant difference were found between the groups (p = 0.08). The probability of achieving a major molecular response (MMR) in the total group by the 3rd year of asciminib treatment was 42 %; the probability of achieving MMR in the Cp and 2Cp / Cp ACA+ groups was 44 and 33 %, respectively; no significant difference were found between the groups (p = 0.6).In univariate analysis, significant favorable factors for achieving MMR were the molecular response at the start of asciminib therapy ≤10 %, the best molecular response in prior TKI therapy ≤1 %, and the absence of prior ponatinib treatment. In multivariate analysis, a history of ponatinib therapy was an independent significant factor for achieving MMR with asciminib therapy (p = 0.02; hazard ratio 12.08).Conclusion. The therapy results of patients in initially unfavorable 2Cp / Cp ACA+ group were comparable with Cp group in terms of both survival rates and probability of achieving responses. However, given the small number of patients in our cohort, the asciminib efficacy in patients with T315I+ CML with ACA and a history of progression requires further investigation. A factor that significantly reduced the probability of achieving MMR during asciminib treatment was a history of ponatinib therapy.

Background. FMS‑like tyrosine kinase 3 (FLT3) gene mutations are the most frequently detected genetic aberrations in adult patients with newly diagnosed acute myeloid leukemia (AML), identified in approximately 30 % of patients. The addition of midostaurin, an FLT3 tyrosine kinase inhibitor, to standard therapy and after allogeneic hematopoietic stem cell transplantation (allo‑HSCT) improves overall (OS) and event‑free survival (EFS). Aim. To evaluate the effect of adding midostaurin to standard therapy in adult patients with FLT3‑mutated AML. To evaluate the impact of allo‑HSCT performed in first complete remission on the survival of patients treated in combination with midostaurin. Materials and methods. The study enrolled 276 patients with newly diagnosed AML with FLT3 mutation. 153 of them received combination therapy with midostaurin, 123 – first‑line therapy without FLT3 inhibitors. In the combination therapy group allo‑HSCT in first complete remission was performed in 35 (22.9 %) patients. Results. The response rate was higher in the combination therapy group and was 84 % versus 66 % in the control group (p < 0.01). with a median follow‑up of 19 (2–130) months, the median OS was not achieved in both groups. The 18‑month OS was 60 % (95 % confidence interval (CI) 50–69) in the midostaurin group and 53 % (95 % CI 43–61) without it (p = 0.12). Median EFS was 11.6 months (95 % CI 9.1–13.8) and 6.7 months (95 % CI 4.2–10.2) respectively (p = 0.046). The 18‑month EFS was 33 % (95 % CI 24–42) and 31 % (95 % CI 23–40). In multivariate analysis, factors associated with worse EFS were older age and FLT3 internal tandem duplication. Age, leukocytosis at the time of diagnosis, and the presence of unfavorable cytogenetic abnormalities had a negative effect on EFS. Midostaurin therapy was associated with EFS improvement. In a landmark analysis with a 6‑month time point, OS was 89 % (95 % CI 69–96) in the allo‑HSCT group versus 38 % without it (95 % CI 20–55) (p = 0.002). EFS was 75 % (95 % CI 50–88) and 13 % (95 % CI 5–26), respectively (p <0.001). Conclusion. The addition of midostaurin to standard treatment contributes to an increased response rate and improved survival in patients with FLT3‑mutated AML. Allo‑HSCT in first complete remission remains the preferred option for remission consolidation in patients treated with tyrosine kinase inhibitors.

Background. Patients with acute myeloid leukemia (AML) are predisposed to infectious complications (IC). Single nucleotide polymorphisms in genes can affect the function and/or expression of the proteins they encode. Since the functioning of the innate immune system is under genetic control, identifying polymorphic variants that reduce the effectiveness of the immune response is a promising method for identifying patients at high risk of severe infections.Aim. To evaluate the relationship between presence of single nucleotide polymorphisms TLR3 C1234G and IL4 C589T with IC frequency in AML patients.Materials and methods. TLR3 C1234G and IL4 C589T polymorphisms were genotyped in 93 patients with AML, of which 77 (82.80 %) – de novo AML, 16 (17.20 %) – AML with previous myelodysplastic syndrome. Patients received 263 chemotherapy courses. Median age was 58 (Q1–Q3: 38–66) years, 50 (53.76 %) were men, 43 (46.24 %) were women. Sepsis and pneumonia were considered severe IC. Allele-specific polymerase chain reaction with detection of amplification products in a 3 % agarose gel was used to genotype single nucleotide polymorphisms in immune response genes.Results. Severe IC were developed in 57 (21.67 %) chemotherapy courses. It was found that in patients with the TLR3 1234GG genotype, compared with carriers of the TLR31234CC genotype, the frequency of severe IC is 4.8 times lower (odds ratio 0.21; p = 0.022). Severe IC occurred 2.3 times more often in heterozygous carriers of the IL4 C589T polymorphism than in homozygous carriers of the C allele (odds ratio 2.29; p = 0.025). In multivariate analysis, taking into account age, gender and severity of neutropenia, the TLR31234GG and IL4 589CT genotypes variants remained independent predictors of IC.Conclusion. The TLR3 1234CC and IL4589CT genotypes are associated with the risk of severe IC in AML patients.

Malnutrition is a significant problem for patients with hematological neoplasms and solid tumors, serving as a negative prognostic and predictive factor that reduces the effectiveness of anticancer therapy and worsens survival outcomes.The article discusses the role of nutritional support in improving treatment outcomes, reducing complications, and enhancing the quality of life for cancer patients. It reviews current clinical guidelines for the implementation of nutritional support in oncology and oncohematology, underscoring the necessity of early intervention and continuous monitoring to prevent and address nutritional deficiencies. Various methods of nutritional support, including oral, enteral, and parenteral nutrition, are also discussed, with an emphasis on the importance of a personalized approach to meet the individual needs of patients.

Background. One approach to improving overall and relapsefree survival for patients with acute leukemia is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The probability of relapse after allo-HSCT in acute leukemia patients may be influenced by many factors, including the presence of minimal residual disease (MR) before allo-HSCT. Aim. To evaluate the relationship between MR presence in first complete remission and probability of relapse after allo-HSCT in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).Materials and methods. The study included 241 patients: 143 with AML and 98 with ALL (30 patients with Ph-positive leukemia, 22 patients with T-cell ALL and 46 patients with B-cell ALL) who received allo-HSCT at the National Medical Research Center for Hematology from September 2015 to July 2021. The MR analysis was performed using flow cytometry. Statistical analysis was performed using BIM SPSS v. 23 (SA).Results. Univariate event analysis revealed that in AML patients, poor prognosis was most associated with MRD-positive status before allo-HSCT (hazard ratio (HR) 10.249 (95 % confidence interval (CI) 4.137–25.388); p ˂ .0001). Multivariate analysis included MRD-positive status before allo-HSCT (HR 9.161 (95 % CI 3.513–23.652); p 001), ELN risk (HR 4.423 (95 % CI 1.764–11.092); p ˂ 0.0034), and transplant source (bone marrow/peripheral stem cells) (HR 3.068 (95 % CI 1.188–7.924); p ˂ 0.0156). Three-year overall and relapse-free survival of AML patients in the first complete remission with MRD-positive status were statistically significantly worse than in patients with MRD-negative status (overall survival 43 % versus 78 %; p = 0.0004; relapse-free – 26 % versus 67 %; p ˂ .0001). In the univariate event analysis, it was found that MRD-positive status before allo-HSCT (HR 4.180 (95 % CI 1.333–13.112); p = 0.0142) was most associated with an unfavorable prognosis in ALL patients. In the multivariate analysis, only the MRD status before allo-HSCT was selected (p = 0.0005). The overall survival of MRD-positive ALL patients, although significantly worse, did not differ statistically significantly from that of MRD-negative patients who received allo-HSCT in the first complete remission (28 % versus 68 %; p = 0.09).Conclusion. MRD analysis before allo-HSCT helps to identify a group of patients with an extremely high risk of relapse after transplantation, which dictates the need to correct therapeutic tactics regarding the choice of donor, conditioning regimen, immunosuppressive therapy, or early prophylactic antirelapse therapy.