Background. Hodgkin lymphoma is one of the highly curable types of cancer, but patients with advanced stages remain at risk of early progression and late chemotherapy effects. Aim. To evaluate the efficacy of first-line treatment for patients with newly diagnosed Hodgkin lymphoma in the Republic of Sakha (Yakutia). Materials and methods. We provided a retrospective analysis of 33 patients (17 women and 16 men, median age 42) with newly diagnosed Hodgkin lymphoma, who were treated in 2019–2024 (follow up to 01.06.2025). In the first-line treatment, depending on the stage and prognostic group, the following regimens were used: ABVD (doxorubicin + bleomycin + vinblastine + dacarbazine), BEACOPP-esc, BEACOPP-14 (cyclophosphamide + doxorubicin + etoposide + dacarbazine + bleomycin + vincristine + prednisolone), BV-AVD (brentuximab vedotin + doxorubicin + vinblastine + dacarbazine) and IVDG (idarubicin + vinblastine + dacarbazine + gemcitabine). Statistical analysis performed using programs StatTech v.4.8.5 и R v.4.4.1. Results. Complete remission was achieved in 27 (87.1 %). Early relapse and progression were observed in 3 (9.7 %) patients. In patients with early stage 3-year overall survival and progression-free survival were 100 %, in advanced stage – 3-year overall survival – 95 %, progression free survival – 79.7 %. The most common side effects were grade 4 neutropenia in patients treated with BEACOPP-14 / esc (75.0–85.7 %) and peripheral polyneuropathy in patients treated with BV-AVD (45.5 %) which was in most cases reversible. There were no cases of refractoriness and relapse in patients, treated with BV-AVD at the time of analysis. Conclusion. Results of this study confirm the efficacy of modern chemotherapy regimens and compatible with the results of other large international studies. However, limited acceptance to PET-CT makes it difficult to realize risk-adapted protocols and optimization of treatment intensity. Long-term efficacy assessment requires additional studies with longer follow-up periods in larger population.

In spite of success in pediatric acute lymphoblastic leukemia treatment, there are disease variants, where survival rates significant lower. Such unfavorable rare examples may include Ph-positive and BCR::ABL1-like acute lymphoblastic leukemia. Complex molecular and genetic diagnosis, make use substantially full range of methods (including in some cases next generation sequencing) allow correct diagnosis and make indications for targeted drugs – ruxolitinib in cases of JAK / STAT activation or dasatinib, if ABL1-kinase activated. Intensive chemotherapy with targeted drugs increased treatment effectiveness and admit withdraw from previously obligatory option – allogeneic hematopoietic stem cell transplantation. Nevertheless, for clinical recommendations in BCR::ABL1-like acute lymphoblastic leukemia treatment it is necessary to combine core facilities experience and cooperative studies.

Background. Lymphoblastic lymphomas (LBL) are an aggressive variant of non-Hodgkin’s lymphomas (NHL), which ranks second in frequency among non-Hodgkin’s lymphomas in children. According to international data, the effectiveness of LBL therapy in children reaches 85 %. In Russia, information on the treatment results for this disease is extremely limited. Aim. To present preliminary data on the results of LBL therapy in children in Russia. Materials and methods. The study included 392 pediatric LBL patients, treated in 57 specialized hospitals of the Russian Federation from 1999 to 2024. Results. The overall and event-free survival rates were 83 % (95 % confidence interval 78–88) and 70 % (95 % confidence interval 64–78), respectively. In addition, the analysis revealed a high frequency of thrombotic complications (29 % of all patients), especially in cases of T-cell LBL. No significant differences in disease outcomes were found between tumor immunophenotypes, the type of asparaginase, and the stage of the disease. A separate analysis of the results of LBL therapy according to the ALL IC-BFM 2002 / 2009 protocols (146 patients) with stricter criteria for the response to induction therapy (tumor reduction of more than 70 %) and early chemotherapy intensification with high-dose blocks at the N. N. Blokhin National Medical Research Center of Oncology showed the event-free and overall survival of about 90 %. The Cox regression model of the dependence of therapy outcomes on residual tumor volume at the end of induction in the main cohort of patients did not reveal an association between residual tumor volume and overall survival (p = 0.2), but there was a statistical association with event-free survival (p = 0.006). Discussion. This paper presents preliminary data from the first multicenter study of LBL therapy in pediatric patients in the Russian Federation. According to our data, LBL survival rates in the Russia should be improved. An important problem in the treatment of LBL in children is therapy complications, especially the high incidence of thrombosis. In this regard, anticoagulant prophylaxis is recommended for patients with LBL, especially with the T-cell phenotype and the presence of risk factors. Further studies are also needed to identify high-risk patients for the development of new personalized therapy approaches. Conclusion. The paper presents preliminary results from the first multicenter clinical study of LBL therapy in children in Russia, indicating the necessity of treatment approaches improvement for increase a treatment effectiveness.

Background. Minimal residual disease (MRD), as determined by immunophenotyping, is an indicator of therapy response and a marker of relapse in many hematological diseases. There are some foreign publications devoted to the assessment of the residual tumor population using multicolor flow cytometry in Waldenstrom’s macroglobulinemia (WM). A characteristic feature of WM is the infiltration of bone marrow by two tumor populations from one tumor clone: clonal B-lymphocytes and clonal plasma cells. The study of these two aberrant populations was only possible using flow cytometry. In 90 % of WM cases, the L265P mutation of the MYD88 gene is detected: it is a diagnostic marker and is much less common in other lymphomas. Aim. To investigate the residual tumor clone characteristics in WM patients, their correlation with progression, assess the relationship between the monoclonal immunoglobulin M dynamics and MRD status, as well as between the presence of the MYD88 mutation at onset and the rate of tumor clone reduction. Materials and methods. Patients underwent immunophenotypic analysis of bone marrow cells at disease onset and at follow-up time points post-induction using multicolor flow cytometry. The following antigens were investigated for B-cells: surface CD19, CD22, CD20, CD45, and CD27, as well as cytoplasmic λ and κ immunoglobulin M antigens. For plasma cells, the following were assessed: surface CD38, CD138, CD27, CD45, CD81, and CD19, along with cytoplasmic λ and κ immunoglobulin M antigens. Standard methods of descriptive statistics and graphical visualization were used to analyze the results. To evaluate the dynamics of aberrant cell populations, multivariate statistical methods were employed, accounting for repeated measures within the same participants. The same methods were applied to study the association of the MYD88 gene mutation with the dynamics of these parameters. Results. Heterogeneity of the residual tumor clone was revealed, which could be represented by three variants of tumor populations: only aberrant B cells; only aberrant plasma cells; and populations of B- and plasma cells. Different reduction rates of residual aberrant B- and plasma cells were observed after the end of induction therapy: in the 1st month after treatment, the number of aberrant B cells decreased 1.4 times faster than plasma cells. The long-term persistence phenomenon of trace immunoglobulin M secretion after induction therapy even in MRD-negative patients was revealed (70 % cases). A relationship was noted between the presence of L265P mutation of the MYD88 gene at the disease onset and the number of residual B cells. In patients without a MYD88 gene mutation at the disease onset, MRD-negative B-cell status was achieved by the first month after the end of induction. No relationship was found between the presence / absence of the MYD88 gene mutation and the residual tumor plasma cell population. Patients with MRD-positive status in any combination (only aberrant B cells; only aberrant plasma cells; and populations of B- and plasma cells) demonstrated a higher probability of disease progression compared to the MRD-negative group. Conclusion. The use of multicolor flow cytometry to detect residual neoplastic B-cell and plasma cell populations provides additional insights into the depth of remission, the rate of tumor cell reduction, and the heterogeneity of the residual malignant clone.

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.

Background. Multiple myeloma (MM) is a malignant lymphoproliferative disorder characterized by tumor plasma cells infiltrating the bone marrow. The pharmaceutical industry for the treatment of MM is experiencing a boom, characterized by the emergence of new-generation targeted drugs. It is important to describe the differences in the binding pattern of monoclonal antibodies to the CD38 protein and to analyze the treatment outcomes of MM patients treated with isatuximab, depending on various biological characteristics of the disease. Aim. To analyze the literature data on the isatuximab mechanism of action on tumor plasma cells, the features of monoclonal antibodies use depending on various factors and present a clinical observation of the isatuximab therapy in ММ patient and concomitant chronic obstructive pulmonary disease (COPD). Materials and methods. For this review, PubMed databases, clinical trial registries, and meeting libraries were searched from inception to December 20, 2025, using the terms reflecting multiple myeloma, isatuximab, daratumumab. We analyzed publications devoted to studying the mechanism of action of CD38 monoclonal antibodies and examining the efficacy of isatuximab in the treatment of multiple myeloma, depending on various factors. Our experience with the IsaPd regimen in a patient with relapsed / refractory MM and concomitant COPD is presented. Results. Isatuximab is the only CD38 antibody capable of inducing direct tumor cell apoptosis. The 1q abnormality did not affect survival in ММ patients treated with isatuximab-containing regimens. Due to limited complement-dependent cytotoxicity, isatuximab may be a preferred option for patients with COPD or asthma. The article describes our experience of isatuximab therapy in MM patient with COPD. The patient was diagnosed with MM in 2015 at the age of 57. Induction therapy consisted of bortezomib- and lenalidomide-containing regimens; an antitumor response was not achieved. Hematopoietic stem cell mobilization was performed after the DHAP regimen (cisplatin, cytarabine, dexamethasone) in combination with granulocyte colony-stimulating factor. To overcome resistance, therapy including carfilzomib was administered, achieving a very good partial remission. Autologous hematopoietic stem cell transplantation (melphalan 200 mg / m2) was then performed, followed by local radiation therapy to the plasmacytoma area, resulting in complete remission. Subsequently, due to relapse, therapy including ixazomib and lenalidomide was prescribed. In 2021, due to MM progression, sixth-line anti-relapse therapy with the IsaPd regimen was initiated. Despite COPD with frequent exacerbations requiring bronchodilator therapy, the patient tolerated isatuximab satisfactorily, with no adverse reactions. Twelve courses of therapy were completed, achieving partial remission. Conclusion. Monoclonal antibodies to CD38 are being integrated into induction therapy protocols for MM patients. This article describes the isatuximab mechanism of action and presents experience using IsaPd as a sixth-line therapy in a patient with MM and COPD. Along with a favorable safety profile, we also observed high treatment efficacy.

Background. Current approaches to treating acute T-cell lymphoblastic leukemia (T-ALL) in adults have achieved significant results, with approximately 60 % of patients recovering after first-line therapy. However, treatment of relapsed and refractory forms of T-ALL remains an unresolved issue, especially given the lack of targeted agents for this disease. Relapsed T-ALL deserve special attention, as they demonstrate conversion of the initial immunophenotypic variant, i. e., a change in the phenotype of tumor cells. Cases of the complete tumor clone replacement – a phenomenon known as “lineage switch” – have been described. This phenomenon is diagnosed in 6–9 % of all relapses and is more commonly observed in children. In cases of an acute leukemia variant conversion, it is extremely difficult to determine the etiology of the second event: are the blast cells the same leukemic clone or should this aspect be considered within the context of the development of a secondary malignancy associated with previous therapy. An equally important issue in this group of patients is the selection of effective treatment programs. Aim. To analyze long-term treatment outcomes in relapsed and refractory T-ALL forms, to assess the likelihood of immunophenotypic variant change (second event) during relapse in T-ALL patients, and to identify risk factors for the development of this phenomenon. Materials and methods. The study included 34 patients with T-ALL who were enrolled in the ALL-2016 study from 2017 to 2024 and who had relapsed or had a primary refractoriness. Of these, 27 (79 %) were male and 7 (21 %) were female. The median age at the time of relapse / second event was 32 (18–54) years. Eighteen patients underwent next-generation sequencing to identify mutations in genes associated with clonal hematopoiesis. Targeted sequencing of the ASXL1, DNMT3A, and TET2 genes was performed. Results. The 2-year overall survival rate for T-ALL patients after relapse or refractoriness diagnosis was 13 %. Immunophenotypic variant change during relapse in T-ALL patients treated according to the ALL-2016 protocol was diagnosed in 18 % (n = 6): 5 patients developed acute myeloid leukemia, 1 patient developed myelodysplastic syndrome with monosomy 7, with subsequent transformation to acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. All patients diagnosed with immunophenotypic variant change during relapse initially had karyotype abnormalities, and 80 % of them were diagnosed with complex karyotype changes. The 2-year overall survival in patients with immunophenotypic variant change was 0 %, and in patients without variant change – 16 % (p = 0.82). In 2 of 5 patients, the “lineage switch” phenomenon was confirmed at relapse: identical mutations in the DNMT3A and ASXL1 genes were detected, the same as those present at the onset of T-ALL. In the group of patients in whom no changes in the immunological characteristics of the tumor clone were observed at relapse, mutations in genes associated with clonal hematopoiesis were detected in 3 (23 %) patients (p = 0.87). In the group of patients with immunophenotypic variant conversion, at disease onset early immunophenotypic variants (ETP and near-ETP) were detected in 5 of 6 patients, and the thymic variant of T-ALL was verified in only 1 (17 %) patient. Conclusion. Long-term treatment outcomes for relapsed / refractory T-ALL remain unfavorable. Rare cases of immunophenotypic variant conversion in T-ALL during relapse are described. A high risk of disease relapse with immunophenotype shift has been confirmed in a group of patients with early T-ALL (ETP and near-ETP), characterized by complex karyotypic changes at onset.

Background. Malnutrition is an aggravating factor in hematopoietic stem cell transplantation (HSCT). Due to the need for the intestinal microbiome protection, which is a key element in homeostasis and is under complex negative effects, a theory aimed at liberalizing dietary restrictions is being developed, which creates the basis for improving the patient’s self-feeding and leads to a number of positive outcomes. Aim. To evaluate the infectious and immunological safety of a modified diet in HSCT. Materials and methods. From 2022 to 2023 at the Raisa Gorbacheva Memorial Research Institute 406 allogeneic HSCT recipients over 18 years old, who followed a low-bacterial (LBD) (n = 177) or modified diet (MD) (n = 229) were enrolled to the randomized trial. The concept of LBD included generally accepted anti-infective restrictions in HSCT, the absence of gluten, lactose, and yeast-containing products. Under MD, only the principles of anti-infective measures were maintained in the preparation, storage, transportation and dishes consumption, and the prohibition of a sharply limited list of foods that are difficult to digest and capable of mechanically injuring the oropharynx and gastrointestinal tract mucous membrane. Results. The patient groups were homogeneous in diagnosis, graft source, HLA-compatibility between the recipient and the donor, conditioning regimen intensity and graft-versus-host disease prophylaxis, except for the age: MD group – 42.3 years, LBD group – 38.4 years; p = 0.009. The one-year overall survival was similar in both groups: 72 % for MD and 75 % for LBD; p = 0.6. Relapse-free one-year mortality was comparable between the groups: 8.7 % for MD versus 9.1 % for LBD; p = 0.9. Graft engraftment at day 30 did not differ: 83 and 92 %, respectively; p = 0.2. The incidence of graft-versus-host disease grade 3–4 was 3.4 % in the MD group and 6.8 % in the LBD group, respectively; p = 0.14. The incidence of bloodstream infections at day 30 was lower in the MD group (14.4 %) compared with the LBD group (45.2 %), respectively; p 0.001. Conclusion. Using the example of the presented patient cohort who underwent allogeneic HSCT, the use of MD has potential advantages over LBD in the form of a tendency to reduce bloodstream infections and the severe graft-versus-host disease incidence. Further studies with a large number of participants are needed to confirm these findings.

Background. Current approaches to the treating BCR::ABL1-negative B-cell lymphoblastic leukemia (B-ALL) patients are aimed at incorporating targeted agents into chemotherapy regimens to improve the efficacy of the first-line therapy. Rituximab was one of the first such drugs to be used and shown to improve survival in B-cell lymphoproliferative disorders. Its inclusion in treatment regimens for BCR::ABL1-negative B-ALL remains controversial. Aim. To determine the prognostic value of CD20 expression on tumor cells in adult patients with BCR::ABL1-negative B-ALL treated according to the ALL-2016 protocol. Materials and methods. The study included 143 patients with BCR::ABL1-negative B-ALL who received treatment from December 2016 to February 2024 as part of the multicenter RALL-2016 trial (ClinicalTrials.gov, NCT03462095). The median patient age was 30 (18–55) years, with a male: female ratio of 71 (50 %):72 (50 %). Immunophenotyping of bone marrow blast cells using flow cytometry was performed in all patients at the disease onset. The presence of the CD20 marker on tumor cells was considered positive if its expression was ≥20 %. From September 2024 to September 2025, four patients received treatment according to the R-RALL-2016m protocol (ALL-2016m including rituximab). Results. In the RALL-2016 study, the frequency of CD20 expression in BCR::ABL1-negative B-ALL was 37 % (53 of 143). Five-year overall survival in BCR::ABL1-negative B-ALL with CD20 expression was 73 %, compared to 68 % in patients negative for this marker (p = 0.9405). Three-year relapse-free survival was 73 and 70 % in the presence and absence of CD20 expression, respectively (p = 0.7944). All patients (4 of 4) achieved bone marrow remission after phase I induction therapy according to the R-RALL-2016m protocol, and 75 % achieved negative minimal residual disease status at the end of induction therapy. Conclusion. In adult patients with BCR::ABL1-negative B-ALL, the inclusion of rituximab may improve long-term survival outcomes by more rapidly achieving clinical and hematological remission and increasing the rate of minimal residual disease negativity after induction therapy. Continued follow-up of patients receiving the new protocol is needed to assess the likelihood of late complications and long-term outcomes.