Background. The key goal of autologous hematopoietic stem cell transplantation (auto-HSCT) is to overcome bone marrow failure, which complicates high-dose chemotherapy. In 2024, 2,790 HSCTs were performed in Russia, 61 % of which were autologous and 39 % allogeneic. Transplant activity in the country has increased by 46 % over the past 5 years. Aim. To evaluate the immediate and long-term outcomes of auto-HSCT in patients with hematologic malignancies treated over the past 6 years (2020–2025) in the High-Dose Chemotherapy Department with the Bone Marrow Transplantation Unit at the P. A. Herzen Moscow Oncology Research Institute. Materials and methods. This retrospective observational study included data from 187 patients who underwent auto-HSCT at the P. A. Herzen Moscow Oncology Research Institute. For the analysis, patients were divided into 3 nosologic groups: multiple myeloma (MM) – 127 (68 %), non-Hodgkin’s lymphoma (NHL) – 31 (16.6 %), and classical Hodgkin’s lymphoma (cHL) – 29 (15.4 %) patients. The median age ranged from 33 to 59 years depending on the nosology. The study assessed the parameters of CD34+ cell mobilization, conditioning regimens, hematological toxicity, overall survival (OS), and progression-free survival (PFS). Survival analysis was performed using the Kaplan–Meier method. Results. A total of 203 auto-HSCT procedures were performed, including 16 (7.9 %) tandem transplants for MM. The median of collected CD34+ cells was 8.1 × 106 / kg in MM, 9.4 × 106 / kg in cHL, and 7.6 × 106 / kg in NHL. Hematopoiesis was restored within comparable time frames in all groups (median agranulocytosis duration was 9–12 days). With a median follow-up of 20–25 months, the 2-year PFS rates were 91.6 % (MM), 92.0 % (cHL), and 81.6 % (NHL); 2-year OS was 96.3 % (MM), 100 % (cHL), and 85.6 % (NHL). Patients with MM showed a significant improvement in the response after transplantation (the proportion of complete responses increased from 9.4 to 61.4 %; p = 0.003). Conclusion. The results of our single-center study demonstrate the high efficacy and acceptable safety profile of auto-HSCT, comparable to global data. Further development of high-dose therapy programs, optimization of mobilization, and the introduction of new maintenance therapy regimens are promising areas for improving treatment outcomes for patients with hematological malignancies in the Russian Federation as a whole.
Background. Infectious complications remain a leading cause of early transplant-related mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly during the period of febrile neutropenia. Despite advances in transplantation techniques and supportive care, the optimal strategy for empirical antibacterial therapy in this high-risk population remains controversial, especially in resource-limited settings. Aim. To evaluate the incidence and spectrum of infectious complications, their impact on early mortality after allo-HSCT, and to assess the effectiveness and safety of an escalation-based empirical antibacterial therapy strategy in a single transplantation center with limited resources. Materials and methods. A single-center retrospective study included 45 adult patients who underwent allo-HSCT between 2023 and 2025 (acute myeloid leukemia – 21, acute lymphoblastic leukemia – 15, aplastic anemia – 8, myelodysplastic syndrome – 1). All patients received a uniform conditioning regimen based on fludarabine and melphalan (FluMel140). The incidence of febrile neutropenia, bloodstream infections, sepsis and septic shock, intensive care unit admission, and early mortality (≤30 days post-transplant) were analyzed. All patients received empirical antibacterial therapy following an escalation strategy. Microbiological identification was performed using VITEK 2 COMPACT and VITEK MS PRIME systems. Results. Febrile neutropenia occurred in 100 % of patients. Recurrent febrile neutropenia was observed in 44 % of cases, requiring escalation of antibacterial therapy to carbapenems. Microbiologically documented bloodstream infections were identified in 13 % of patients. Sepsis with subsequent septic shock developed in 22 % of patients and was associated with 100 % mortality in this subgroup. Gram-negative pathogens predominated among fatal infections, with Klebsiella pneumoniae and Pseudomonas aeruginosa being the most frequently identified organisms. Late colonization with Klebsiella pneumoniae was observed in all patients who died from infectious complications. Conclusion. Infectious complications remain the principal cause of early mortality after allo-HSCT. An escalation-based empirical antibacterial therapy strategy represents a feasible and reproducible approach in the majority of allo-HSCT recipients. However, in patients with a high infectious risk profile and colonization with multidrug-resistant organisms, this strategy may be insufficient. The obtained results highlight the need for individualized empirical therapy, enhanced microbiological monitoring, and optimization of conditioning regimens, particularly in resource-limited transplant centers.
Background. Thrombopoietin receptor agonists are considered second-line therapy and are prescribed to patients with insufficient response or intolerance to first-line therapy. These drugs, which stimulate platelet production by activating the thrombopoietin receptor, are effective and safe for both short-term and long-term treatment of immune thrombocytopenia. They provide high response rates in 70–80 % of patients and sustained remission in 10–30 %. The response to long-term use of thrombopoietin receptor agonists lasts for 6–8 years or more and allows for the reduction or discontinuation of corticosteroid and immunosuppressant use, as well as a halving of the incidence of bleeding. Aim. To evaluate the efficacy of the thrombopoietin receptor agonist avatrombopag in patients with immune thrombocytopenia. Materials and methods. The study included 45 patients with immune thrombocytopenia who received avatrombopag orally once daily, starting with a dose of 20 mg and subsequently titrated to achieve and maintain a platelet count of at least 50 × 109 / L. Statistical data were processed using GraphPad Prism 9, and differences between pre- and post-therapy were assessed using the Wilcoxon signed-rank test (p 0.05). Results. The results of the study demonstrate a statistically significant increase in platelet counts among patients with immune thrombocytopenia treated with avatrombopag. Conclusion. The use of avatrombopag appears justified as a second-line treatment for immune thrombocytopenia.
Aim. To evaluate the structure and effectiveness of therapy for newly diagnosed diffuse large B-cell lymphoma (DLBCL) in adults in real clinical practice according to the Moscow Oncology Registry data. Materials and methods. Data from 1060 patients with newly diagnosed DLBCL from the Moscow Oncology Registry who received treatment from 2022 to 2025 in a Moscow healthcare setting were retrospectively analyzed. The median age was 69 years. The majority of patients were in the older age group (60.4 %), with advanced disease stages (70 %), non-GCB subtypes (60 %), and high risk according to the international prognostic index (67 %). Of all patients included, 62.1 % received immunochemotherapy according to the R-CHOP program (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone), 12.6 % received R-DA-EPOCH (rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin), 2.6 % received intensive regimens, 14.7 % received R-miniCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone in reduced doses), 7.8 % received RB (rituximab, bendamustine) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone). Results. In the overall patient cohort (n = 1060), the objective response rate was 79.7 % (n = 845). Complete metabolic response was achieved by 66.4 % (n = 704) of patients. The complete response rate varied depending on the treatment regimen: in the R-CHOP group it was 68.4 % (n = 451), when using R-DA-EPOCH – 69.4 % (n = 93), intensive regimens – 89.3 % (n = 25). Among patients receiving R-miniCHOP, complete response was achieved in 62.2 % (n = 97) of cases, while in the RB / R-CVP group this rate was the lowest and amounted to 45.8 % (n = 38). With a median follow-up of 24 months, the 2-year overall survival in the total group was 70 % (95 % confidence interval 67–73), and the 2-year progression-free survival was 44 % (95 % confidence interval 40–48). Conclusion. Results of first-line DLBCL therapy efficacy analysis indicate unsatisfactory treatment outcomes, particularly in the high-risk group for early progression. We suggest that biologically targeted antitumor therapy based on the identified tumor genotype represents the most promising clinical approach for patients with newly diagnosed DLBCL.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematologic disorder whose pathogenesis is primarily driven by the formation of a cell clone (the PNH clone) lacking surface protective glycoproteins (CD55 and CD59), activation of the alternative complement pathway, and complement-mediated destruction of erythrocytes within blood vessels (intravascular hemolysis). This process underlies the main clinical manifestations of PNH – hemolytic anemia and thrombotic complications. The introduction of eculizumab, a C5 complement inhibitor, into clinical practice in 2007, which blocks the mechanism of intravascular hemolysis, revolutionized the course and prognosis of PNH. However, 30–45 % of patients continue to experience anemia and require replacement blood transfusions after 6 months or more of regular C5 inhibitor therapy. It has been established that the most common cause of a suboptimal treatment response is extravascular hemolysis, which is based on opsonization of PNH erythrocytes by C3b complement fragments followed by phagocytosis and degradation of these cells by macrophages in the liver and spleen. To suppress the mechanism of extravascular hemolysis, inhibitors of the proximal complement pathway have been developed, including the C3 inhibitor pegcetacoplan, which was registered in Russia in 2023 under the trade name Empaveli. The drug inhibits the activity of C3 and C3b complement components and thereby blocks the entire complement activation cascade, providing suppression of both intravascular and extravascular hemolysis. This article presents the first Russian experience of treating nine PNH patients with suboptimal response to C5 inhibitor therapy with pegcetacoplan. All nine patients demonstrated an average increase in hemoglobin levels of 25 g / L from baseline, achieving transfusion independence. The article also provides a detailed description of three clinical cases of particular interest.
additional measures to ensure the immunological safety of allogeneic transfusions. Aim. To study the features of ensuring the immunological safety of allogeneic transfusions in patients with hematological malignancies. Materials and methods. For the period 2020–2024, the results of immunohematological studies of 10,276 blood samples from patients requiring individual selection of erythrocyte-containing components of donor blood were analyzed. Of these, 1129 (10.9 %) were oncohematological patients; 28 (0.3 %) were patients with established refractoriness to platelet concentrate transfusions requiring individual selection of this concentrate, of which oncohematological diseases were observed in 26 cases. All necessary studies were carried out at the immunological reference center of the Novosibirsk Clinical Blood Center. Results. The proportion of oncohematological patients who required individual selection of erythrocyte-containing blood components was 10.8 % for patients with newly detected anti-erythrocyte antibodies and 11.1 % for those with previously established antibodies. In patients with hematological malignancies, polyspecificity of antibodies is significantly more common (83.1 % of all cases of polyspecificity) and difficult to identify (61.7 % of samples with unknown specificity). The selection of a single red blood cells dose requires significantly (2.2 times) more studies and compatibility testing, extended typing, and significant reserves of erythrocyte-containing blood components for clinical use. The effectiveness of individual selection of erythrocyte-containing blood components in an immunological reference center for oncohematological patients was 98.2 %. Conclusion. Centralization of immunological testing at the Novosibirsk Clinical Blood Center has ensured the effectiveness of individual selection for patients with alloimmunization and antibody production to clinically significant antigens of erythrocyte-containing blood components in 99.7 % of cases, and individual selection of platelet concentrate for patients with transfusion refractoriness in 92.8 % of cases, including for patients with anti-HLA antibodies in 71.4 % of cases.
Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive non-Hodgkin’s lymphoma. Despite advances in therapy, including targeted therapy, 30–40 % of patients experience a primary refractory or relapsed disease with a poor prognosis. This publication presents a literature review of current approaches to treating patients with refractory and relapsed (r / r) DLBCL and a clinical case of a patient with r / r DLBCL using multiple lines of therapy, including CAR-T cell therapy (4SCAR70, anti-CD70) and bispecific antibodies (glofitamab). During glofitamab therapy, the patient developed loss of CD20 expression, which is one of the mechanisms of resistance to anti-CD20 targeted therapy and occurs in 34 % of patients with progression against bispecific antibodies. Loss of CD20 expression limits further use of anti-CD20 targeted therapy, including re-use of glofitamab and other CD20 / CD3 bispecific antibodies. Five courses of VIPOR followed by allogeneic hematopoietic stem cell transplantation were administered as salvage therapy. At the time of the most recent assessment, the achieved complete response with complete donor chimerism is maintained, and the patient is under dynamic observation for three years. There is currently no standard treatment strategy for patients with loss of CD20 expression after therapy with bispecific antibodies. Allogeneic hematopoietic stem cell transplantation is a potential therapeutic option for this category of patients. Alternative treatment strategies include the use of antibody conjugates directed at CD79b (polatuzumab vedotin) or CD19 (loncastuximab tesirin), a combination of lenalidomide and tafasitamab, as well as targeted agents depending on the lymphoma molecular subtype. This clinical case demonstrates the possibility of achieving a complete response in a patient with refractory and relapsed DLBCL following loss of CD20 expression during glofitamab therapy. Treatment of these patients requires a personalized approach based on prior therapies, disease status, expression of target antigens, and the availability of therapeutic options. Further research is needed to determine the optimal treatment sequence, develop strategies to overcome resistance, and identify alternative therapeutic targets.
The availability of medication is directly determined by the ability to reimburse its costs, which determines the appropriateness of anemia therapy and the prognosis for cancer patients. Aim of the work was to assess the potential for financing medical care for patients with malignant neoplasms and anemia using compulsory medical insurance. A review of payment methods for medical care for patients with malignant neoplasms and anemia using compulsory medical insurance funds in accordance with Russian legislation was conducted. Models of medical care organization are identified depending on the suspected etiology of anemia. Suitable payment methods for each model are substantiated. For patients who develop anemia after starting anticancer therapy, there are several options for paying for medical care using compulsory medical insurance: 1) a single clinical statistical group with antitumor therapy [ds19.157–ds19.180; st19.182–st19.202], as well as a patient treatment complexity coefficient sl005 for a concomitant disease – unspecified anemia (International Classification of Diseases, 10th revision code D64.9) (i.e. without an established etiology); 2) 1st clinical statistical group (1st insurance event) with antitumor therapy [ds19.157–ds19.180; st19.182–st19.202]; 2nd clinical statistical group (2nd insurance event) with treatment for anemia of specified etiology (except International Classification of Diseases, 10th revision code D64.9) [ds05.001–ds05.002; st05.001–st05.002]. A decision-making algorithm has been developed to ensure a legal mechanism for the use of treatment complexity coefficient, within the framework of which erythropoiesis-stimulating drugs for unspecified anemia are prescribed before the diagnosis of anemia in malignant neoplasm is established. Compliance with the proposed decision-making algorithm before submitting an insurance claim for payment with treatment complexity coefficient s1005 for unspecified anemia opens up opportunities for insurance coverage of erythropoiesis-stimulating drugs in oncology medical organizations, which increases the availability of drug treatment for patients insured under compulsory medical insurance.
Background. Acalabrutinib, a second-generation Bruton tyrosine kinase inhibitor, has demonstrated high efficacy and an improved safety profile in randomized clinical trials in patients with chronic lymphocytic leukemia. However, real-world data remain essential to confirm its effectiveness and tolerability in broader, less selected patient populations, particularly in regions where such data are limited. Aim. To evaluate the effectiveness, safety, and quality of life in patients with chronic lymphocytic leukemia treated with acalabrutinib in routine clinical practice in Russia. Materials and methods. This prospective, multicenter observational study included adult patients with chronic lymphocytic leukemia who received acalabrutinib monotherapy according to physician decision. Patients were followed for up to 96 weeks. Primary endpoints included real-world progression-free survival and safety. Secondary endpoints included overall survival (OS), response rates, factors influencing treatment outcomes, and quality of life assessed using the FACT-Leu (Functional Assessment of Cancer Therapy – Leukemia) questionnaire. Survival was analyzed using the Kaplan–Meier method. Results. The analysis included 85 patients (median age 65.5 years), of whom 78.8 % received therapy for relapse. High-risk features were frequent, including TP53 aberrations in 73 % of tested patients and unmutated IGHV in 65 %. At week 16, overall response (complete remission + partial remission) was achieved in 79 % of patients. By 18 months, complete response was observed in 65 % and partial response in 28 % of patients. With a median follow-up of 22.4 months, progression was recorded in 3 patients, and median OS was not reached; 1- and 2-year OS rates were 95 % and 90 %, respectively. Survival was not associated with TP53 status, IGHV status, or line of therapy. Diabetes mellitus was associated with inferior OS, likely due to infectious complications. Adverse events were reported in 21.2 % of patients, most commonly infections. Cardiovascular toxicity was infrequent. Quality of life (FACT-Leu scale) significantly improved over time (p 0.001). Conclusion. In a real-world Russian cohort, acalabrutinib demonstrated high efficacy, rapid and durable responses, and a favorable safety profile, including in patients with high-risk disease and significant comorbidity. These findings support the broad applicability of acalabrutinib in routine clinical practice.
Background. Waldenstrom’s macroglobulinemia (WM) is a rare indolent lymphoma characterized by bone marrow infiltration by lymphoplasmacytic cells and monoclonal immunoglobulin (Ig) M secretion. For primary diagnosis and assessment of remission depth, allele-specific polymerase chain reaction (AS-PCR) is also used to quantitatively assess the p.L265P mutation of the MYD88 gene with a sensitivity of 0.1 %. The treatment response is assessed according to the international NCCN (National Comprehensive Cancer Network) criteria, which are based on the regression of clinical symptoms and a decrease in serum monoclonal IgM concentration. However, this approach does not always reflect complete elimination of the tumor clone. Since the serum IgM concentration, determined by electrophoresis, can be maintained even in the absence of tumor cells in the bone marrow (up to 6 months), it is possible to use methods based on tumor clone characteristics, such as multicolor flow cytometry (MFC). The usefulness of minimal residual disease (MRD) monitoring using the MFC method, which is the standard for assessing remission depth in many other hematological malignancies, in WM has not been clearly determined. Aim. To compare the MRD-positive / negative status by MFC with the presence / absence of MYD88 gene p.L265P mutation by AS-PCR and clinical and laboratory characteristics of WM patients. Materials and methods. The study included 70 patients with WM who received treatment at the National Medical Research Center for Hematology between 2017 and 2025. The diagnosis was established in accordance with international criteria (2-IWWM (2nd International Workshop on Waldenstrom’s Macroglobulinemia) 2002, NCCN 2025) and Russian clinical guidelines. To assess the remission depth, 13-color MFC and AS-PCR to detect MYD88 gene p.L265P mutation in bone marrow aspirate were used. Results. Achieving MRD-negative status was statistically significantly more often associated with a lower baseline tumor burden (B-cell infiltration, IgM and β2-microglobulin levels) and higher hemoglobin and platelet counts. Regression of clinical manifestations (hepatosplenomegaly, B-symptoms) was not a clear predictor of achieving MRD-negative status. The study results confirmed the prognostic value of MRD monitoring by MFC for assessing the progression probability. The presence of MYD88 gene p.L265P mutation has not been confirmed as an unfavorable prognostic factor and continues to be studied. Conclusion. MFC is a universal method for both primary diagnosis and MRD monitoring in WM. Comprehensive MRD monitoring using MFC and AS-PCR for MYD88 gene mutation has prognostic value in WM. Achieving a double negative status (MFC– / MYD88–) is an objective marker of maximal complete remission.
AL amyloidosis (ALA) is a disease characterized by the deposition of immunoglobulins monoclonal free light chains fragments with impaired organ function. Despite advances in the treatment of plasma cell dyscrasias, determining optimal approaches to treating ALA patients remains a challenging task. Research results and real-world clinical practice data indicate the advantage of using a combination of daratumumab with a bortezomib-containing regimen over other programs in achieving an antitumor response, increasing progression-free survival, while remaining a highly effective treatment option with a favorable safety profile in most patients. It is advisable to study the prognostic role of minimal residual disease in ALA patients and its correlation with the achieved hematological and organ responses at different treatment stages, as well as to search for new biological markers for patients’ risk stratification and optimization of antitumor therapy. Clinical case of a patient with stage II ALA are presented. After six cycles of Dara-VCD (daratumumab, bortezomib, cyclophosphamide, and dexamethasone), a very good partial hematologic response was recorded. Despite the fact that the patient had previously received VCD (bortezomib, cyclophosphamide, and dexamethasone) and daratumumab alone in the second line, significant treatment efficacy, along with a significant improvement in overall condition and quality of life, was achieved only with the use of bortezomib-containing therapy in combination with an anti-CD38 antibody.
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. 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.
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. 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. 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.
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. 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. 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.
