Follicular lymphoma (FL) is one of the most common types of non-Hodgkin’s lymphomas. The tumor is characterized by a wide range of clinical manifestations, ranging from indolent forms to early transformation and progression with a poor prognosis. The search for clinically significant genetic changes is essential for personalized risk assessment and treatment selection. The CREBBP gene is frequently mutated in this type of lymphoma, with changes occurring at the level of the earliest tumor precursor cells. However, the prognostic and diagnostic significance of the CREBBP gene mutation status in FL has not been fully established. In this study, we analyzed sequencing data of exons 22–30 of the CREBBP gene in 86 samples from patients with different grades of FL (1–3B), including those in the 3A–3B subgroup without the t(14;18) translocation. We also investigated the prognostic significance of CREBBP gene mutations in relation to the treatment options, namely high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT/auto-HSCT) and conventional chemotherapy programs (CCT). It was found that FL patients with a single missense mutation in the KAT domain of the CREBBP gene experienced an extremely low number of early adverse events related to lymphoma and had better long-term survival rates, regardless of treatment option. In contrast, when comparing patients with FL without a missense mutation in the KAT domain or those with multiple mutations in the CREBBP gene, overall and progression free survival were worse, and early progression and histological transformation were more common. Compared to standard therapy, patients who underwent HDCT/auto-HSCT in the FL 1–3B (14;18)-positive group without a single missense mutation in the KAT domain had better survival rates and lower rates of transformation and early progression. In addition, among patients with FL 3A–3B (14;18)-negative, we found that there were no cases of a missense mutation in the KAT domain of the CREBBP gene. This suggests that a single missense mutation in the CREBBP gene may be a feature that discriminates 14;18-positive FL with a favorable prognosis from a high-risk disease. FL 3A–3B (14;18)-negative may represent a distinct variant with different biology and underlying mechanisms of development compared to classical FL.

Introduction. Lymphoma from cells of the marginal zone in some cases can manifest itself only at the stage of histological transformation into aggressive lymphomas, including diffuse large B-cell lymphoma (DLBCL). Aim: to present a clinical observation of lymphoma transformed at the time of diagnosis from marginal zone cells to DLBCL. Main findings. A case report of relapsed DLBCL in the submandibular area is presented, which was observed for 11 years without treatment. At the time of relapse, a 81x43x88 mm mass in the lower lobe of the right lung with SUV max up to 19.27 was identified. Atypical resection of the lower lobe of the right lung was performed. Based on histology and immunohistochemistry, a diagnosis of DLBCL transformed from marginal zone B-cell lymphoma was established, with PCR confirming the identity of the clone of indolent and aggressive B-cell lymphoma. The patient received R-CHOP plus lenalidomide therapy and achieved complete remission.

Introduction. Primary mediastinal large B-cell lymphoma (PMBCL) is a rare non-Hodgkin lymphoma. Considering the immunophenotype of PMBCL, which differs from diffuse large B-cell lymphoma (DLBCL), Microsatellite Repeat (MSR) aberrations in regions flanking PD-L1/PD-L2 and CIITA genes were investigated. Aim: to study the prevalence of MSR aberrations in 19 loci of the COrDIS Plus panel and in the regions of the PD-L1/PD-L2, CIITA genes in PMBCL and DLBCL, and to compare it with the expression level of PD-L1 and HLA-DR in PMBCL. Materials and methods. The study included 137 patients, 86 (62,8%) with PMBCL and 51 (37.2%) with DLBCL. The analysis was conducted using the standard COrDIS Plus panel, which includes a set of primers for 19 loci of tetranucleotide repeats. The allelic imbalance (AI) of MSR close to the PD-L1/PD-L2 genes (9p24.1) (n = 68/86 (79.1%) for PMBCL, n = 36/51 (70.6 %) for DLBCL) and CIITA (16p13.13) (n = 71/86 (82.6 %) for PMBCL, n = 29/51 (56.9 %) for DLBCL) was investigated using STR analysis. Patients with homozygous inheritance for each of the studied markers were excluded from further analysis due to the inability to assess loss of heterozygosity (LOH). The expression of PD-L1 and HLA-DR was assessed by immunohistochemistry in 27/86 (31.4 %) PMBCL patients. Results. Homozygosity for both markers near the PD-L1/PD-L2 genes was found in 5/68 (7.4 %) of PMBCL patients and 10/36 (27.8 %) of DLBCL patients (p = 0.008). Aberrations of MSR flanking the PD-L1/PD-L2 genes were detected in 33/63 (52.4%) of PMBCL patients and 5/26 (19.2 %) of DLBCL patients (p = 0.003; OR 5.8; 95% CI [2.8-18.7]). Homozygosity for both markers near the CIITA gene was identified in 8/71 (11.3%) of PMBCL patients and 7/29 (24.1%) of DLBCL patients (p = 0.13). AI near the CIITA gene was found in 24/63 (38.1 %) of PMBCL patients, while no changes in the CIITA region were observed in the DLBCL group (p = 0.0001; OR 14.3; 95% CI [2.8-262.5]). Using the COrDIS Plus panel, the frequencies of tetranucleotide repeat aberrations did not significantly differ between PMBCL and DLBCL (p = 0.78 for LOH, p = 0.17 for EMAST). No correlation was found between MSR aberrations near the PD-L1/PD-L2 and CIITA genes and the expression levels of PD-L1 and HLA-DR (p = 0.402 and 0.668, respectively). Conclusion. A statistically significant more frequent alteration in the MSR marker profile of the PD-L1/PD-L2 and CIITA gene regions was found in PMBCL patients compared to DLBCL. Chromosomal microarray analysis in 2 out of 3 PMBCL cases revealed genetic aberrations involving the PD-L1/PD-L2 and/or CIITA genes, and AI of these genes was observed simultaneously with the MSR profile evaluation. This confirms the different pathogenesis of these diseases and suggests that the presence of AI in these loci indicates the involvement of these genes in the pathogenesis. There is no correlation between AI in the PD-L1/PD-L2 and CIITA gene regions and the expression of PD-L1 and HLA-DR, respectively.

Introduction. Lymphomatoid papulosis is a CD30-positive lymphoproliferative disease with primary skin lesions. One of the therapeutic options is the use of anti-CD30 monoclonal antibody brentuximab vedotin. Aim - to present the clinical observation of the effective treatment of lymphomatoid papulosis in a 6-year-old patient using brentuximab vedotin. Main findings. In patient K., 6 years old, after suffering from acute respiratory viral infection, the appearance of rashes was noted, located mainly on the skin of the extremities, represented by single inflammatory papules of round shape, up to 6-8 mm in diameter, dense consistency upon palpation, with a smooth surface and a pinpoint area of white necrosis in the center of individual elements. A biopsy of one of the elements was performed. According to histological examination, a diagnosis was established: lymphomatoid papulosis, type A. Due to the ineffectiveness of therapy using topical glucocorticosteroids, oral administration of prednisolone, the patient was treated with brentuximab vedotin. A partial complete response was achieved.

The development of National clinical guidelines on diagnosis and treatment of Ph-negative myeloproliferative neoplasms provides the knowledge basis for decision making in diagnosis, therapy, prevention, and rehabilitation in compliance with evidence-based medicine principles in order to ensure appropriate medical care in a particular clinical setting. The clinical guidelines underly the choice of optimal methods of diagnosis, therapy, prevention, and rehabilitation as part of a patient’s medical care, the development of criteria for the assessment of medical care quality, medical care standards, medical care procedures, setting standards on equipment and management of diagnostic and therapeutic procedures, and provision of continuous medical education and advanced training for healthcare professionals. In 2013, a working group was formed to develop and formulate clinical guidelines on the treatment of myeloproliferative neoplasms. These guidelines were first published in 2014, afterwards they were revised and republished. The dynamic development of current hematology presupposes constant updating of knowledge and implementation of new diagnosis and treatment methods in clinical practice. In this context, clinical guidelines present a dynamic document to be continuously amended, expanded, and updated in accordance with scientific findings and new requirements of specialists who are directly involved in treatment activities. The present edition is an upgraded version of clinical guidelines with updated information on classification, diagnosis, prognosis, current methods of therapy, and their efficacy and tolerability assessment. The guidelines are intended for oncologists, hematologists, healthcare executives, and medical students.

Introduction. The R-NHL-BFM-90 protocol has been successfully used for the treatment of Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL) in children and adolescents, as well as adult T-cell lymphomas. The protocol was modified for the treatment of adult patients with de novo nodal DLBCL. Aim: to evaluate the efficacy and toxicity of the R-mNHL-BFM-90 and R-DA-EPOCH-21 protocols in adult patients with de novo nodal DLBCL with 2 or more signs of poor prognosis, as well as to determine the role of auto-HSCT in the consolidation of remission. Materials and methods. From 2015 to 2021, 164 patients were evaluated for randomization. The study included 140 patients from 13 Russian medical centers. 89 (76 %) patients with de novo nodal DLBCL: R-DAEPOCH-21 20 (22.5 %) patients; R-DAEPOCH-21 + auto-HSCT 21 (23.5 %) patients; R-mNHL-BFM-90 20 (22.5 %) patients; R-mNHL- BFM-90 performed + auto-HSCT 28 (31.5 %) patients. In the high-intermediate and high-risk group, there were 12 (29.3 %) and 29 (70.7 %) patients on the R-DA-EPOCH-21 + auto- HSCT protocol and 15 (31.2 %) and 32 (66.7 %) on the R-mNHL- BFM-90 protocol + auto-HSCT, respectively. Results. The R-mNHL-BFM-90 protocol proved to be more effective. Complete remission in the high-risk group was achieved in 30 (93.7 %) patients versus 18 (62.0 %), there was no progression versus 3 (10.3 %) patients treated according to R-DA-EPOCH-21 (p = 0.0167). The five-year overall and event-free survival in the high-risk group was 97 % vs. 75 % (p = 0.01) and 97 % vs. 72 % (p = 0.0026), respectively. In the intermediate risk group, the results of therapy did not differ. The toxicity of the R-mNHL-BFM-90 protocol exceeded the toxicity of R-DA-EPOCH-21 only in neutropenic fever (p = 0.04) and grade 3-4 thrombocytopenia (p = 0.0009). Conclusion. The R-mNHL-BFM-90 protocol is effective for the treatment of patients with nodal de novo DLBCL diffuse large B-cell lymphoma of high-risk adults; its toxicity is acceptable. However, on the R-DA-EPOCH-21 therapy, the results of therapy are unsatisfactory. The R-DA-EPOCH-21 protocol with auto-HSCT was more effective than without auto-HSCT, however, due to the small number of patients, the results were unpresentative. The results of therapy according R-mNHL-BFM-90 protocol with auto-HSCT and without auto-HSCT were not differ.

Background. Mycosis fungoides (MF) is classified as an orphan disease. Due to the rarity of pathology, and until recently the absence of an expert group and a specialized reference center for cutaneous lymphomas in Russia, possible treatment options for MF are presented by listing them without recommendations on the preferred indications for one or another option. This creates difficulties in choosing treatment methods and assessing their effectiveness.Aim. To characterize current treatment methods and their results in MF patients who were observed or received consultative and diagnostic care at the National Medical Research Center for Hematology.Materials and methods. The study included 210 patients: 115 with early disease stages and 95 with advanced stages.Results and conclusion. The most common treatment options were for early stages – local therapy, interferon therapy and systemic chemotherapy (CT), for advanced stages – combination therapy with interferon (+ PUVA therapy, methotrexate), interferon monotherapy and systemic CT. The frequency of systemic chemotherapy use in all lines of MF treatment was 21 %. When integrating statistical analysis using the probability of achieving an antitumor response, switching to 2nd line therapy, and accumulated incidence, the negative results of using chemotherapy in the MF treatment were clearly demonstrated.For the first time in Russia, a real practical situation of the applied MF treatment options is presented on our own large sample of patients. As the first line of therapy, the most common options were immunotherapy and phototherapy, however, in 12.4 % of cases, the use of systemic CT was registered, which is unjustified and leads to a decrease in the time to the next line of treatment and an increase in the cumulative incidence of adverse events. As a result of the use of non-chemotherapeutic approaches (interferon, etc.), the 3-year relapse-free survival rate is about 40 %, after chemotherapy – 9.4 %. Secondand third-line therapy provided more varied options, including combination treatment with interferon and methotrexate, as well as gemcitabine monotherapy, targeted therapy with brentuximab vedotin, and epigenetic therapy in the 3rd line. Studies with targeted agents in this patient population have demonstrated improved clinical outcomes, highlighting the need for their early use to achieve the best results.

Introduction. Peripheral T-cell lymphomas (PTCL) — a rare group of lymphoproliferative diseases characterized by an aggressive course and an unfavorable prognosis. The group is represented by heterogeneous nosological forms, in which standard treatment options lead to unsatisfactory results. Aim: to present the protocols for the treatment of PTCLMain findings. In total, 12 years of experience in the treatment of 724 patients with T-cell lymphomas (430 patients with primary cutaneous forms, 110 patients with leukemic variants and 184 with peripheral T-cell lymphomas) has been accumulated. The treatment results and therapeutic algorithms were analyzed. In the general group of patients, the 3-year overall survival (OS) and relapse-free survival (EFS) were 76 % and 70 %, respectively. The best treatment results were achieved in the groups of intestinal T-cell lymphoma, specifically (EATL), and angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell ALK-positive lymphoma (ALCL ALK+), and the worst — in the group of ALCL ALK- (5-year EFS 31 %). High-dose chemotherapy under the NHL BFM-90 program in the treatment of ALK+ ALCL allows achieving 10-year OS and EFS 87 % and 84 %, respectively, but the less toxic CHOEP program was not inferior in effectiveness: 5-year OS and EFS amounted to 93 % and 88 %, respectively. High survival rates of patients with EATL were achieved with the use of high-dose chemotherapy according to the LB-M-04 program followed by auto-HSCT in the first line of therapy: 5-year OS and EFS amounted to 79 % and 74 %, respectively. The positive role of AITL maintenance therapy has been shown: 5-year OS and EFS during its implementation amounted to 75 % and 49 % versus 41 % and 20 % in the absence of it. In the protocols for the treatment of extranodal NK/T cell lymphoma, radiation therapy was used in the first line of therapy, 5-year OS and EFS were 60 % and 42 %, respectively. The role of autologous hematopoietic stem cell transplantation (auto-HSCT) in all PTCL was evaluated: 5-year OS and EFS were 82 % and 58 % compared with 67 % and 49 % without auto-HSCT. The transplantation of allogeneic hematopoietic stem cells (allo-HSCT), even in the treatment of relapses of the disease, has shown its effectiveness: 9 out of 11 patients are alive and remain in remission of the disease.

Aim. To determine the prognostic value of t(14;18)(q32;q21) in follicular lymphoma (FL) of grades 1–3А, to assess the chemotherapy efficacy in “t(14;18)+ FL” and “t(14;18)– FL” patients, and to analyze the cases of ineffective therapy. Materials & Methods. The retrospective/prospective study carried out at the National Research Center for Hematology in the period of 2001–2022 enrolled 362 patients with newly diagnosed FL of grades 1–3А. Their risk stratification was based on predictive models FLIPI and PPI3 (Personalized Predictive Index[1]). The patients were 30–81 years of age (median 52 years). There were 225 women and 137 men. They received the following regimens: R-B (n = 80), R-CHOP (n = 189), R-CHOP (4 cycles) + R-DHAP (2 cycles) (n = 28), and R-CHOP (4 cycles) + R-DHAP (2 cycles) + auto-HSCT in the first-line therapy (n = 65). For 2 years, maintenance rituximab therapy was administered to all the enrolled patients, whichever drug chemotherapy they received. Standard cytogenetic analysis and FISH were carried out in 265/362 (73 %) patients. Results. Patients were divided into two comparable groups: “t(14;18)+ FL” (n = 196) and “t(14;18)– FL” (n = 69). Patients without cytogenetics/FISH (n = 97) were excluded from the analysis. In patients without t(14;18), poor prognostic factors, such as grade 3А (p = 0.003) and Ki-67 > 35 % (p = 0.001), were identified significantly more often, and also high PPI3 risk was reported (p = 0.008). No differences (p = 0.84) were detected during FLIPI risk stratification of patients. Bone marrow lesions were observed significantly more often in “t(14;18)+ FL” compared to “t(14;18)– FL” (p = 0.002). The chemotherapy outcomes, such as 2-year EFS and OS, appeared to be considerably worse in “t(14;18)– FL” compared to “t(14;18)+ FL” patients. Conclusion. The group of FL patients with t(14;18) appeared to be most numerous and more prognostically favorable. Immunochemotherapy regimens R-B and R-CHOP are more justified in the first-line therapy of FL with low PPI3 risk. Therapy outcomes were comparable in efficacy. In intermediate and high PPI3 risk FL patients with t(14;18), the most effective first-line therapy was the one with consistent administration of R-CHOP, R-DHAP, and auto-HSCT. Based on the results of this study, FL of grades 1–3А without t(14;18) can well be considered to be a prognostically unfavorable variant of this malignant lymphoid tumor. The rate of early relapses/progression after the standard immunochemotherapy (R-B and R-CHOP), according to our data, is 60 %. In patients with newly diagnosed FL who received consistent administration of R-CHOP, R-DHAP, and auto-HSCT in the first-line therapy, this rate drops to 30 %. Our results clearly indicate the need for new FL treatment approaches.

A rare clinical observation of advanced myeloid sarcoma developed through blast transformation of post-polycythemia vera myelofibrosis as extramedullary manifestation of acute myeloid leukemia affecting larynx, laryngopharynx, trachea, soft tissues of the neck, pleura, and skeletal bones is presented.

Introduction. Relapses of primary mediastinal large B-cell lymphoma (PMBСL) with involvement of the central nervous system (CNS) are usually incurable. Therapy tactics in patients with PMBCL with relapse in the CNS have not been defined. Aim: to present clinical observations of the treatment of relapses of PMBCL with CNS involvement using the “R-PML-CNS-2022” protocol. Main findings. Two clinical observations of patients with relapses of PMBCL with involvement of the CNS are presented. In both cases, the “R-PML—CNS-2022” protocol was used as a second-line treatment, and a complete remission of the disease was achieved. In the first case, within 6 months after auto-HCT, maintenance therapy with pembrolizumab was performed. Complete remission of the disease continues for 15 months. In the second observation, maintenance therapy with pembrolizumab was also started, however, due to the development of autoimmune complications after 2 cycles, treatment was discontinued. Complete remission of the disease continues for 13 months. Conclusion. The development of a new strategy for the treatment of relapses of PMLCL with CNS lesion according to the “R-PML—CNS-2022” protocol is a potentially curative approach in this group of patients.

Introduction. The follicular lymphoma (FL) is the most common indolent lymphatic tumor with high sensitivity to immunochemotherapy un most cases. Although overall survival (OS) is generally long, the disease is characterized by multiple relapses. High-dose chemotherapy (HDCT) with transplantation of autologous hematopoietic stem cells (auto-HSCT) is used for recurrent FL. Aim: to evaluate the efficacy and safety of HDCT with aHSCT in the first line of FL therapy; identify risk factors for disease progression and refractoriness. Material and methods. A prospective single-center study (conducted from May 2015 to January 2023) included 35 patients aged 18–65 years (median 43) with PL 1–3A grade t(14;18)+ with stages III–IV or stage II with bulky, having at least one criterion for the need to start therapy (according to GELF). Patients were treated according to the FL-2015 protocol: 4 R-CHOP, 2 R-DHAP and BeEAM with auto-HSCT. The primary endpoint was the rate of overall response (OR) and/or complete remission (CR) at the end of chemotherapy. Secondary end points were 3-year survival rates: OS, relapse-free survival (RFS), progression-free survival (PFS), and event-free survival (EFS). Minimal residual disease (MRD) in blood and/or bone marrow was assessed by PCR based on immunoglobulin heavy chain (IGH) gene rearrangements and/or BCL2::IGH rearrangements. Statistical analysis (by intent to treat) was performed on January 12, 2023. Results. 86 % of patients had stage IV tumor and 79 % had 3–5 FLIPI factors. After the end of treatment, OR and PR were 90 % and 90 %, the incidence of POD24 was 3 %. After the end of induction (4 courses of R-CHOP), MRD-negativity was achieved in 77 % and 53 % of patients as determined by PCR-IGH and BCL2::IGH. After the full completion of the FL-2015 protocol, MRD was not detected in 96 % of patients (according to PCR-IGH). Three-year overall survival, disease-free survival, progression-free survival and event-free survival were respectively: 90 %, 90 %, 95 % and 85 % (with the same standarderror of 9 %) at a median follow-up (by inverse Kaplan-Meier estimate) of 19 months (range: from 1 to 91 months) There were no deaths due to early toxicity within 100 days of auto-HSCT. Prognostically unfavorable independent statistically significant (р < 0.01; Wald test; hazard ratio > 1) predictors of progression and refractoriness according to the results of multivariate analysis using the Fine-Grey competing risk model (р = 0.052 for the model) were: bone marrow disease, ECOG high risk, patient age > 50 years, stage 4 disease, elevated serum lactate dehydrogenase and B-symptoms. Conclusion. The use of HDCT with auto-HSCT in the first line in patients with FL is highly effective and can significantly reduce the incidence of POD24 and early mortality from the tumor. The study is ongoing.

Background . Multiple myeloma (MM) is a plasma cell tumour, which could be followed by formation of bone plasmacytomas. Bone plasmacytoma is plasma cells proliferate, developed in a medullar cavity, which could destroy cortical layer of a bone and escape to the surrounding tissues. Biological characteristics of tumour substrate hypothetically could influence the clinical course of MM. Aim . To compare clinical and laboratory parameters of newly diagnosed MM depending on the presence or absence of bone plasmacytomas. Materials and methods . A retrospective study included 40 patients with newly diagnosed MM aged from 24 to 63 years. 21 patients are diagnosed with bone plasmacytomas. In another 19 patients MM proceeded without plasmacytomas. As an induction therapy all patients were treated with bortezomib-containing regimens. 10 patients were also received immunomodulatory drugs. 34 patients underwent autologous hematopoietic stem cell transplantation (auto-HSCT). Results . When comparing laboratory parameters at the onset of MM, patients with bone plasmacytomas showed minor lesion of bone marrow, higher haemoglobin concentration and low paraprotein secretion. When comparing MM clinical parameters it turned out that the frequency of achieving a significant antitumor response after induction therapy was reliably lower in patients with bone plasmacytomas: 28.6 % versus 68.4 % (p = 0.038). Auto-HSCT made it possible to deepen the antitumor response in group of patients with bone plasmacytomas. On +100 day auto-HSCT significant antitumor response was registered in 52.6 % of patients. For correct assessment of antitumor response the dynamics of plasmacytoma measurements is very important. When using only the data of immunochemical analysis for response assessment, the frequency of achieving a significant antitumor response is overestimated, this is not an adequate reflection of clinical situation. Conclusion . MM with bone plasmacytomas has some clinical and laboratory features. Auto-HSCT is highly efficient method of treatment of this patient cohort. Assessment of antitumor response in patients with bone plasmacytomas only by the data of immunochemical analysis is insufficient and may serve as a reason for choosing the wrong therapeutical tactics.

Introduction. When establishing a diagnosis of thrombotic thrombocytopenic purpura (TTP) for the first time, other diseases occurring with thrombocytopenia may be misdiagnosed. Aim: to analyze diagnostic difficulties and errors of TTP. Materials and methods. In total, 54 patients (44 women and 10 men) aged 18 to 83 years (median 33 years), who were diagnosed TTP from 2019 to 2023, were included in the study. Anamnesis, baseline hemoglobin, platelets, erythrocytes, lactate dehydrogenase and bilirubin serum concentrations, pre-established diagnoses, treatment, and outcomes were analyzed. Results. Initially TTP was suspected only in 19 (35 %) patients. In 12 out of 54 patients immune thrombocytopenia (ITP) was initially misdiagnosed. Fisher-Evans syndrome was initially suspected in 3 patients. In sporadic cases, myelodysplastic syndrome, systemic lupus erythematosus / antiphospholipid syndrome, autoimmune hemolytic anemia were initially suspected. Among 15 women with associated with pregnancy TTP in 8 (53.3 %), HELLP syndrome was initially misdiagnosed. In total, 12 (22.2 %) of 54 TTP patients died. In 11/12 non-survival patients, TTP treatment was never started, because the doctors were waiting for the ADAMTS13 test results. A case report of Sequential Immune Thrombocytopenia (ITP) and TTP in the same Patient is described. Conclusion. When thrombocytopenia is combined with hemolysis and in the absence of multiple organ pathology, it is difficult to differentiate ITP and TTP without examining the plasma activity of ADAMTS113. With a combination of ITP and TTP in the same patient, the study of ADAMTS13 plasma activity makes it possible to identify the leading mechanism of thrombocytopenia and choose treatment tactics.

This article presents the first case of VEXAS syndrome identified in the Russian Federation as well as characteristics of currently known clinical manifestations and treatment approaches. The clinical observation described is an impressive example of how the identification of a new pathogenic mutation can change the understanding of the classification, diagnosis and treatment of previously known immunoinflammatory diseases. Thus, in refractory forms of relapsing polychondritis, neutrophilic dermatosis, atypical forms of vasculitis, inflammatory joint diseases or undifferentiated systemic inflammatory syndrome, especially when associated with macrocytic anemia and myelodysplastic syndrome, VEXAS syndrome should be suspected and genetic testing should be performed to exclude the autoinflammatory nature of the existing condition.

Aim. To determine the incidence and prognostic value of mutations in exon 16 of EZH2 as well as those of polymorphism с.1582-21А>G (rs2072407) in EZH2 in patients with follicular lymphoma (FL) grades 1–3А in relation to morphologic and cytogenetic tumor characteristics. Materials & Methods. The prospective cohort study conducted by the National Research Center for Hematology from January 2017 to April 2021 enrolled 80 patients with newly diagnosed FL grades 1/2 and 3А. The median follow-up was 53 months. Molecular and cytogenetic analyses were based on biopsy samples of lymph nodes obtained before chemotherapy. The mutation status of exon 16 in EZH2 and the presence of intronic polymorphism rs2072407 in EZH2 were examined by Sanger sequencing method. Translocation t(14;18)(q32;q21) was detected by karyotyping or FISH. Results. Mutations in exon 16 of EZH2 (mutEZH2) were identified in 10/80 (13 %) patients. All patients showed missense mutation in codon 646 of EZH2. Translocation t(14;18) was detected in 45/80 (56 %) cases. Poor outcome in the cohort with no t(14;18) was observed 3 times more often than in the group of patients with t(14;18) (p = 0.0001). The presence of t(14;18) was associated with favorable prognosis irrespective of either the mutation status of exon 16 in EZH2 or the FL grade. The analysis of the polymorphism rs2072407 status yielded the following genotypes: AA in 24 % (n = 19), AG in 42 % (n = 34), and GG in 34 % (n = 27) of cases. The variants АА and AG were associated with higher risk of death (hazard ratio 2.9; 95% confidence interval 1.2–10.6; p = 0.01), whereas the genotype GG was associated with wtEZH2 (10 % vs. 37 %) and favorable prognosis (p = 0.065). Conclusion. Significant biological markers for favorable prognosis in FL appeared to be the presence of t(14;18)(q32;q21) and GG genotype of polymorphism rs2072407 in EZH2. The previously identified prognostic factors (grade 3А, bulky tumor lesions > 6 cm, Ki-67 > 35 %, and a short interval between symptom onset and chemotherapy start) were incorporated into a new unified personalized predictive (index PPI) FL model by supplementing it with two additional biological markers: the presence of t(14;18)(q32;q21) and GG genotype of polymorphism rs2072407. This approach may increase the prognostic value of the new personalized design which will provide the basis for risk-adapted algorithms for FL treatment.

Mycosis fungoides (MF) is the most ubiquitous type of cutaneous T-cell lymphoma. MF pathogenesis has not been well studied up to now. Differential diagnosis of the disease, especially at early stages, is complicated and poses a considerable challenge. The present review covers current views on MF pathogenesis and methods of its diagnosis.

Background. Plasmablastic lymphoma (PBL) is a rare variant of large B-cell lymphoma. This disease is usually associated with HIV infection and is predominantly identified in male patients. Tumor lesion is typically localized in oral cavity. PBL is characterized by aggressivity and low rate of long-term survival. Aim. To report a clinical case of a rare localization of PBL with primary impairment of bone marrow in a 19-year-old HIV-negative patient. Materials & Methods. The diagnosis of the disease turned out to be challenging and was based on the results of a multi-step complex immunohistochemical analysis of a bone marrow core biopsy sample. Results. Intensive block-based mNHL-BFM-90 polychemotherapy combined with bortezomib and daratumumab resulted in remission which allowed to perform consecutive autologous and then allogeneic hematopoietic stem cell transplantations. For the lack of immune control of transplant over the tumor the conducted therapy was disappointingly unsuccessful. The patient died in 11 months after diagnosis because of tumor progression. Conclusion. New approaches are definitely called for in order to explore methods of treating this complex disease. A study of mechanisms underlying PBL pathogenesis can contribute to better understanding of tumor biology and personalized choice of chemotherapy.

10 | 2022; 6:S5 and advanced disease were 100%, 94%, and 80% (P<.0001), respectively. The impact of socioeconomic status (SES) on outcomes was analyzed in pts treated with ABVD. The 5-year PFS in higher and lower SES were 75% and 60% (P<.0001). The 5-year OS in higher and lower SES were 90% and 77% (P<0.0001). The fatality ratio during treatment was 5.0% and 1.1% for lower and higher SES (P<0.0001). After adjustments for potential confounders, lower SES remained independently associated with poorer survival (HR 2.10 [1.52–2.90] for OS and HR 1.58 [1.26–1.99] for PFS). Conclusions: This analysis confirmed the predominance of advanced disease and high-risk profile pts. There was an increase in the use of PET and a reduction in RT in recent years. We confirmed that the outcomes are 10–15% lower in Brazil than reported in the literature. SES was an independent factor associated with shorter survival.

Background. Nowadays, hematology is a dynamically developing science due to the in-depth study of the molecular mechanisms of a particular disease. A better understanding of oncohematological diseases biology makes it possible to synthesize new targeted drugs, which have a favorable therapeutic effect. In particular, in multiple myeloma, after the introduction of proteasome inhibitors and immunomodulatory drugs into clinical practice, an improvement in overall survival was observed. However, characteristics of the mechanisms of transformation normal plasma cells into malignant ones are still difficult; therefore, the study of the pathobiological basis of multiple myeloma is currently an urgent task.The objective: to evaluate the possible influence of MAGE-C1 gene expression and the presence of mage-c1 protein in patients with newly diagnosed multiple myeloma on the anti-tumor response after bortezomib-containing therapy.Materials and methods. A prospective study included 33 multiple myeloma patients. The diagnosis was established according to International Myeloma Working Group criteria (IMWG, 2014). In 32 patients the induction therapy included bortezomib-containing courses, in one patient lenalidomide was included in the first-line regimens. The MAGE-C1 gene expression by real-time polymerase chain reaction and mage-c1 protein by immunohistochemistry in plasma cells bone marrow, were determined for all patients at the debut of multiple myeloma. As a control group was examined the bone marrow material of healthy donors.Results. When assessment the statistical relationship between the expression of MAGE-C1 gene and mage-c1 protein, it was found that there was no high expression of mage-c1 protein at low values of MAGE-C1 gene expression. At the same time, high expression of the gene was always associated with protein expression above normal values. The analysis aimed at finding the relationship between MAGE-C1 gene and mage-c1 protein detection and the degree of antitumor response after 6 courses of induction therapy showed that high expression of the studied parameters was associated with a worse response to bortezomib-containing treatment.Conclusion. We confirmed that the results of the two methods were comparable. Single factor analysis showed that patients with decreased MAGE-C1 gene and mage-c1 protein expression levels achieved a significantly higher antitumor response to bortezomib-containing regimens, while high expression was accompanied by refractoriness to bortezomib.