Oncohematology

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. 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. 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 1^st 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. B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is a malignant neoplasm of precursor B-cells characterized by clonal proliferation of lymphoid blasts, which by definition represent immature cells at an early stage of B-lineage differentiation. Despite shared genetic and immunophenotypic features, B-ALL and B-LBL differ in gene expression profiles, clinical presentation, and primary sites of involvement. In rare cases, extramedullary manifestations, including skin involvement, may precede bone marrow infiltration and complicate early diagnosis.

Aim. To assess the role of modern laboratory diagnostic methods in the identification of B-ALL/LBL with cutaneous involvement in Kazakhstan and their impact on patient management.

Materials and methods. Analyzed literature data and presented a clinical case of a 35‑year-old female patient with B-ALL/LBL and primary skin involvement treated at the Kazakh Research Institute of Oncology and Radiology. Laboratory investigations included complete blood count, cytological and flow cytometric immunophenotyping of bone marrow, immunohistochemical examination of a skin biopsy, conventional karyotyping, and fluorescence in situ hybridization. Instrumental studies included ultrasound examination and 18F-fluorodeoxyglucose positron emission tomography/ computed tomography. Treatment was administered according to the ALL-2022 KZ and HyperCVAD protocols.

Results. B-LBL with skin involvement are rare and difficult for diagnosis. Our patient presented with cutaneous lesions followed by bone marrow and lymph node involvement. Integrated morphological, immunophenotypic, and cytogenetic evaluation enabled timely diagnosis. Despite achieving complete remission after first-line therapy, relapse occurred and was associated with immunophenotypic changes, including altered expression of markers of immaturity and B-lineage differentiation, consistent with clonal evolution. Second-line therapy resulted in a subsequent remission, followed by autologous hematopoietic stem cell transplantation performed in Astana after referral to another specialized center.

Conclusion. Our issue demonstrates the diagnostic challenges of rare cutaneous manifestations of B-ALL/LBL and highlights the expanding role of advanced laboratory diagnostics in Kazakhstan, while emphasizing unresolved issues related to early recognition and access to comprehensive molecular profiling.

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. The target therapy have changed chronic myelogenous leukemia (CML) entity from life-threatening to potential curable disease. With the wide range of three generations of tyrosine kinase inhibitors (TKI) we could provide optimal response for the vast majority and switching to treatment free remission (TFR) to substantial proportion of patients. The new inspiration of improving CML treatment results had been got with developing of new class TKIs – STAMP inhibitors with other point of action. The clinical trials of first in class STAMP inhibitor – asciminib demonstrated very rapid and high response rates including deep molecular responses in first line of CML treatment. These data resulted to U. S. Food and Drug Administration approval of asciminib for adult patients with newly diagnosed CML in chronic phase. Despite the several second generation TKIs (TKI2) approved for the first line, the majority of newly diagnosed CML are treated with imatinib in routine clinical practice due to economic and safety considerations. Besides good survival and response rates imatinib treatment give possibility of switching to TFR only for minority of patients. We hypothesized that the high rate of deep molecular responses with asciminib treatment in first line could substantially increase the proportion of CML patient which could be tried to stop treatment in TFR settings.

Aim. To compare the costs of imatinib and asciminib in the first-line of CML treatment with the use of TFR strategy.

Materials and methods. We have used Markov chain approach to compare strategies of first-line CML treatment with imatinib or asciminib with switching to other TKIs in case of intolerance or inadequate response, followed by therapy discontinuation in cases of long-term deep molecular response. Input parameters for transition rates were selected from clinical trials (IRIS, ENESTnd, DASISION, ENACT, CA180013, STIM, FILMC group, 200, Euro-SKI, ASCEND-CML, ASC4FIRST), our own data and expert opinion. Since there is no data on the rate of successful TFR in patients receiving asciminib, we assumed that the success of treatment discontinuation in that case may be comparable to those for TKI2. Prices for consultations, laboratory monitoring and drugs were obtained from insurance programs and published contracts. We selected 800 newly diagnosed patients with CML in Russia per year as the model population. A time interval of 10 years was used. We attempted to estimate the cost of treatment per patient and the total budget burden on the entire national population of CML patients. The total cost included direct costs of diagnostic procedures for diagnosis, monitoring of residual disease effects, the cost of medications (TKIs and concomitant drugs for the treatment of complications), and allogeneic stem cell transplantation. We additionally conducted cost-effectiveness analyses of asciminib and imatinib separately for the costs of achieving successful therapy discontinuation and a comparative analysis of the two treatment regimens. Statistical methods included simulation models.

Results. Rapid and deep molecular responses with asciminib treatment allows an attempt to discontinue therapy in 53.9 % of patients with possible success of final drug discontinuation in 34.0 %, imatinib has lower probabilities: 25.9 and 11.2 % of patients, respectively. The costs of treating one patient and the cumulative costs of diagnostics and therapy of CML at the national level are significantly higher in the case of using asciminib instead of imatinib in the first line of CML treatment. The ratio of the asciminib / imatinib strategies cost ratio over 10 years is 2.38 for one patient and 2.82 at the population level. At the same time, the costs per 1 % probability of successful therapy discontinuation were lower for asciminib (43,448 rubles) than for imatinib (55,472 rubles). The costs of an additional 1 % of therapy discontinuation success in a comparative analysis of asciminib and imatinib was assessed as 37,601 rubles per one patient for one year of treatment or 3,133 rubles per one month of treatment. Sensitivity analysis of the price ratios of imatinib and asciminib showed that parity (equal value of total costs for diagnostics and treatment of one CML patient for ten years) will be as follows: at the current cost of imatinib (8,119 rubles), the equal costs of asciminib is 34,260 rubles; for the proposed cost of asciminib (190,298 rubles), the equal cost of imatinib is 157,200 rubles.

Conclusion. Pharmacoeconomic modeling of diagnostics and therapy of chronic myeloid leukemia can assess the budget burden and its future dynamics at the individual patient, group, and national levels. The results of modeling the use of imatinib and asciminib in the first-line CML therapy showed an almost three-fold higher probability of achieving successful treatment discontinuation, as well as lower costs per 1 % probability of successful TFR when using asciminib compared to imatinib. The results of such modelling can be used in decision making process for the national treatment standards development and budget allowance. There are many limitations of this study due to simulation and stipulation of some important input parameters.