Search

Background. Chronology of granulopoiesis based on periodic hematopoiesis model has been thoroughly studied. However, the pattern of influence of immunotherapy-induced cytotoxic stress on the biological rhythm of a stem cell development requires further investigation. The interaction of antitumor drugs with normal hematopoietic cells is relevant for assessing the intensity of chemotherapy adverse events. Besides, there is a demand for studying hematopoiesis under cytotoxic stress to predict immunological reactivity as a condition for efficacy of immunotherapeutic agents, the effect of which is based on cell immunity. Aim. To study the chronological pattern of leukocyte count dynamics after R(G)-DHAP immunochemotherapy in non-Hodgkin’s lymphomas. Materials & Methods. The dynamics of leukocyte count changes after R(G)-DHAP immunochemotherapy was analyzed using the data of 39 treatment courses in 19 non-Hodgkin’s lymphomas patients. After 18 out of 39 cycles of treatment granulocyte colony-stimulating factor (G-CSF) was administered to prevent granulocytopenia, in other cases the previously planned hematopoietic stem cell mobilization was performed according to the accepted protocol. Results. Time to activation of spontaneous granulopoiesis depends neither on G-CSF stimulation, nor on the total dose of growth-stimulating factor and corresponds on average to Day 10 or Day 11 of the break from the last day of immunochemotherapy. The tendency of shorter agranulocytosis duration on prophylactic use of G-CSF is associated with transient hyperleukocytosis at an early stage after completing immunochemotherapy. Regimens with platinum-based drugs, like R(G)-DHAP, are suggested to be combined with immunochemotherapeutic agents in patients with the failure of first-line chemotherapy. The time interval preceding myelopoiesis activation within the first days of the break between the courses is likely to contribute to the initiation of treatment with immunotherapeutic drugs after second-line chemotherapy. Conclusion. The determination of granulopoiesis dynamics under R(G)-DHAP immunochemotherapy-induced cytotoxic stress enables to plan the optimum G-CSF regimen and to predict the optimum timing of immune antitumor effect combined with chemotherapy.

Aim of the issue was to determine indications for intratecal chemotherapy drugs administration to prevent relapse of diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) involvement.Since January 2009 to December 2018 102 patients with primary nodal DLBCL over 18 years old were treated in the National Research Center for Hematology, Moscow, Russian Federation. Diagnosis were established in all cases according to histological and immunohistochemical studies which made it possible to exclude the transformation of mature B-cell lymphoma into DLBCL.Isolated leptomeningeal involvement of CNS in the debut of the disease was detected in 1 (0.98%) out of 102 patients with DLBCL. Focal brain tissue involvement was not detected in any patient. More than half of the patients (54%) had a high risk of disease recurrence or progression with CNS involvement: in 8 (7.8%) patients had kidney/adrenal involvement, in the same proportion - bone marrow involvement, paranasal sinuses involvement - in 5 (4.9 %), epidural space - in 7 (6.9%) and breast - in 5 (4.9%) of patients. In 82 (80%) patients, a non-GCB (postgerminal differentiation of B-cell analog) molecular subtype of DLBCL was determined.The introduction of chemotherapy drugs into the spinal canal is recommended in isolated cases of leptomeningeal involvement of CNS at the time of DLBCL onset and is carried out according to standard recommendations. Prevention of relapse with involvement of central nervous system using intratecal chemotherapy in patients with nodal form of DLBCL is not indicated due to the absence of cases with disease progression or recurrence into CNS when patients were treated with R-m-NHL-BFM-90, R-DA-EPOCH and R-CHOP protocol.Целью работы является определение показаний к проведению профилактики рецидива диффузной В-клеточной крупноклеточной лимфомы (ДВККЛ) с вовлечением центральной нервной системы (ЦНС) путем введения химиопрепаратов в спинномозговой канал. Материалы и методы. С января 2009 по декабрь 2018 г. в ФГБУ «НМИЦ гематологии» Минздрава России проводилось лечение 102 больным первичной нодальной ДВККЛ старше 18 лет. Всем больным проводили гистологическое и иммуногистохимическое исследования, позволившие исключить трансформацию зрелоклеточной лимфомы в ДВККЛ. Результаты. Вовлечение оболочек головного мозга/нейролейкемия в дебюте заболевания диагностировано у 1 (0,98%) больного. Очагового вовлечения вещества головного мозга не выявлено ни у одного пациента. Более половины больных (54%) имели высокий риск развития рецидива или прогрессии с вовлечением ЦНС: у 8 (7,8%) больных отмечалось вовлечение почек/надпочечников, в таком же проценте - костного мозга, параназальных синусов - у 5 (4,9%), эпидурального пространства - у 7 (6,9%) и молочных желез - у 5 (4,9%) больных. У 82 (80,1%) пациентов определен постгерминальный (из В-клеток постгерминальной дифференцировки - non-GCB) молекулярный подтип ДВККЛ. Заключение. Введение химиопрепаратов в спинномозговой канал показано в единичных случаях, когда в момент манифестации ДВККЛ у больных выявляется вовлечение оболочек/нейролейкемия, и проводится согласно стандартным рекомендациям. Профилактическое введение цитостатических препаратов в спинномозговой канал не показано ввиду отсутствия рецидивов ДВККЛ с вовлечением ЦНС у больных, проходивших лечение как по протоколу m-NHL-BFM-90, так и R-CHOP, R-DA-EPOCH.

Background. TP53 gene mutations impede cell apoptosis and lead to additional oncogenic events contributing to tumor progression. Aim. To assess TP53 gene mutation rate in patients with high-grade B-cell lymphoma double-hit (HGBCL DH) and not otherwise specified (HGBL NOS); to analyse its relationship with disease prognosis. Materials & Methods. Retrospective materials from medical data of 10 HGBL DH and 26 HGBL NOS patients were analyzed. Median follow-up was 26.5 months (range 0.6-160.9 months). Selection was based on the presence of available biological materials (paraffin blocks) for Sanger sequencing of TP53 gene from exon 5 to exon 8 (encoding DNA-binding domain of TP53 gene). FISH analysis of the tumor was performed in all patients to identify translocations involving c-MYC/8q24, BCL2/18q21, and BCL6/3q27 gene locus. To analyze differences between groups χ2 and Mann-Whitney tests were applied. Univariate event analysis (Kaplan-Meier and log-rank tests) and Cox regression analysis were used to assess the influence of molecular markers on the disease prognosis. Results. TP53 gene mutations in lymphoma cells were found in 13 (36 %) out of 36 patients, 10 (77 %) out of 13 mutations were pathogenic. In 8 out of 10 patients with TP53 mutations c-MYC/8q24 gene translocation was identified. Groups with wild (TP53-WT) and mutant (TP53-MUT) types of TP53 gene were similar in terms of main clinical characteristics. Patients with TP53-MUT in tumor cells showed worse 3-year overall survival (OS) compared with the group without TP53-MUT (30 % vs. 73 %; p = 0.026) as well as higher probability of disease progression in the period of 3 years (66 % vs. 15 %; p = 0.004). In multivariate analysis significant OS predictor was the presence of TP53 mutation (p = 0.006). Relapse/ progression probability was higher in combined cases of TP53 mutation and translocation involving c-MYC gene locus (p = 0.0003). Conclusion. Translocation involving c-MYC gene along with TP53 gene mutation in tumor cells can serve as a criterion for dividing HGBL DH and HGBL NOS patients into different lymphoma relapse/progression risk groups.

Aim. To set survival parameters for follicular lymphoma (FL) patients with different PRAME expression levels in tumor cells. Materials & Methods. The study was conducted on samples of lymph nodes, blood, and bone marrow of 34 patients with newly diagnosed FL. PRAME expression levels were measured in tumor cells (centrocytes and centroblasts) by quantitative real-time PCR. The impact of different PRAME expression levels on survival parameters was studied with median follow-up of 29 months. Clinical and laboratory characteristics used for FLIPI-1 and FLIPI-2 calculations in different patient groups were compared. Results. A high (> 5 % against ABL control gene) PRAME expression level correlates with higher Ki-67 activity (p = 0.043) and larger tumor mass (p = 0.04). Survival parameters were worse with high PRAME expression level in FL cells. Combination of both high FLIPI-1/FLIPI-2 risk and high PRAME expression level determines extremely unfavorable prognosis and may result in death. Conclusion. In FL patients high PRAME expression level in tumor cells has negative prognostic value, but only in the presence of parameters determining high FLIPI-1 and FLIPI-2 risk. Juxtaposition of PRAME expression level and FLIPI-1/ FLIPI-2 values enables most reliable prediction of early mortality in FL patients.

Analysis of microsatellite instability (MSI) is a routine study in the diagnostics of solid malignancies. The standard for determining MSI is a pentaplex PCR panel of mononucleotide repeats: NR-21, NR-24, NR-27, BAT-25, BAT-26. The presence of MSI is established based on differences in the length of markers in the tumor tissue and in the control, but due to the quasimonomorphic nature of standard mononucleotide loci the use of a control sample is not necessary in the diagnosis of MSI-positive solid tumors. The significance of the MSI phenomenon in oncohematology has not been established. This paper presents the results of a study of MSI in B-cell lymphomas: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL). We have shown that aberrations of mononucleotide markers occur in these diseases, but the nature of the changes does not correspond to the classical MSI in solid neoplasms. This fact requires further study of the pathogenesis of such genetic disorders. Due to the possibility of ambiguous interpretation of the results of the MSI study for previously uncharacterized diseases, strict compliance with the methodology of parallel analysis of the tumor tissue and the control sample is mandatory.

Background. T-cell lymphomas (T-CL) represent a heterogeneous group of malignant lymphoproliferative disorders characterized by unfavorable prognosis. The cancer-testis PRAME gene is notable for its spontaneous expression in transformed cells as observed in solid tumors, B-cell lymphoproliferative and chronic myeloproliferative diseases. Activity and clinical significance of PRAME in T-CL was not studied before, which determines the relevance and provides ground for the present trial. Aim. To assess the clinical significance of the PRAME gene expression in T-CL. Materials & Methods. PRAME gene expression level was measured in samples of lymph nodes, blood, and bone marrow from 35 T-CL patients. Among them 3 patients received allogeneic hematopoietic stem cell transplantation, and 6 patients received autologous hematopoietic stem cell transplantation. A correlation was established between the PRAME expression in bone marrow and peripheral blood with morphological markers of disseminated disease with bone marrow lesions and leukemic blood. PRAME expression level was correlated with survival parameters and tumor proliferative activity (Ki-67). Results. PRAME activity was observed in 21 (60 %) patients. PRAME hyperexpression is associated with advanced stages of disease (p = 0.0734), bone marrow lesions (p = 0.0289), leukemic blood (p = 0.0187), worsening of the overall survival (OS) (p = 0.0787) and event-free survival (EFS) (p = 0.7185), also after hematopoietic stem cell transplantation (p = 0.2661 for OS and p = 0.0452 for EFS), and with a high Ki-67 expression level (p = 0.0155). Conclusion. PRAME expression in T-CL is often observed and related with unfavorable clinical prognosis.

Background. The V617F mutation of JAK2 is known to manifest in Ph-negative chronic myeloproliferative diseases (cMPD), such as polycythemia vera, thrombocythemia, and myelofibrosis. These diseases not infrequently advance into more aggressive forms up to acute leukemia. As the progression mechanism is still unknown, its study retains a high priority. JAK2 carrying the V617F mutation is believed to cause constant activation of V(D)J recombinase in myeloid tumor cells in cMPD patients. Aberrant activation of V(D)J recombinase in tumor cells in cMPD patients can lead to t(9;22)(q34;q11) chromosomal rearrangement. Aim. To study the expression of BCR-ABL1 resulting from translocation t(9;22)(q34;q11) in cMPD patients at the progression stage in order to test the suggested hypothesis. Materials & Methods. The BCR–ABL1 expression was assessed in peripheral blood granulocytes in cMPD patients by real-time PCR. The JAK2 V617F mutation was identified by quantitative allele-specific PCR. The JAK2 exon 12 mutations were determined using Sanger direct sequencing of PCR products. Results. The BCR-ABL1 expression was discovered in 29 % of patients with cMPD progression. The BCR-ABL1 expression in these patients correlated with hepatosplenomegaly and hyperleukocytosis. Conclusion. In a significant proportion of cMPD patients the disease progression can be associated with activation of the BCR-ABL expression.

Background. Grade 3 follicular lymphoma (FL) is a heterogenetic group of tumors. The selections of patients with similar characteristics of the tumor process is important for classification 3 grade forms of FL and risk stratification, as well as for the development of new therapeutic approaches. Different morphological, immunohistochemical and cytogenetical characteristics of the tumor result in different clinical forms of the disease. Aim. To describe the clinical, morphological, immunohistochemical and cytogenetical characteristics of grade 3 FL and evaluate their prognostic value for R-CHOP-21 chemotherapy. Materials & Methods. We performed retrospective and prospective analysis of morphological, immunohistochemical and genetical characteristics of 93 primary patients with grade 3 FL (21-78 years, median 53 years, women to men - 1:1.4) admitted to National Medical Hematology Research Center from years 2001 to 2016. Morphological and immunohistochemical assessment of the affected lymph nodes and bone marrow biopsy material was performed. Data obtained from the standard cytogenetic and FISH assessment were compared to identify the BCL2 rearrangement. Results. We proposed an algorithm for differential diagnosis of the 2 types of grade 3 FL: de novo FL (n = 22) and transformed FL (n = 21). De novo grade 3 FL had the immunophenotype of CD10- in 19 (86 %) cases, MUM1++ (monomorphically) in 19 (90 %), and BCL-2 in 5 (22 %). It was characterized by the absence of the BCL2 rearrangement (n = 22, 100 %) and bone marrow involvement (n = 14, 67 %) and/or bone marrow involvement (n = 7, 100 %). Third grade FL transformed from grades 1 or 2 had was CD10+ (n = 19, 90 %), MUM1+ (heterogeneously, n = 16, 76 %) or MUM1-(n = 4, 19 %), BCL-2+ (n = 20, 95 %) and had BCL2 rearrangement (n = 19, 90 %). Small cell bone marrow involvement was observed in 71 % of cases, whereas large cell involvement was seen predominantly in de novo FL (p = 0.06). The analysis showed that 5-year relapse-free survival in patients with grade 3 de novo FL after R-CHOP-21 therapy was 87 % compared to 16 % with transformed FL (p = 0.06) for the median 41 months of follow up. Conclusion. We described the morphological, immunohistochemical and cytogenetical characteristics of grade 3 de novo FL and grade 3 FL, transformed from grades 1 or 2. The described variants show different sensitivity to immunochemotherapy.

Mediastinal gray-zone lymphoma (MGZL, lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma) was declared as a separate entity in WHO classification of Tumors of Haematopoetic and Lymphoid Tissues in 2008 and 2017 years. Despite of similar pathomorphological characteristics between primary mediastinal B-cell lymphoma and Hodgkin lymphoma, clinical features and optimal therapeutic approach to MGZL are not clearly defined. Usually MGZL manifests with mediastinal lymphadenopathy, although extranodal lesions often occur (grey-zone lymphoma, GZL). Patients with MGZL have unfavorable prognosis, taking into account high rate of relapse. This article describes two cases of MGZL. First case manifested by arrhythmias due to primary heart involvement. In spite of cardiac failure antracycline-containing chemotherapy (6 courses of R-DA-EPOCH) it allowed to achieve a complete remission and resolving of arrhythmias. Second case was represented by metachronous tumors: primary mediastinal B-cell lymphoma at the time of disease onset and classical Hodgkin lymphoma, NS II, diagnosed after disease progression. Thus, we demonstrated two examples of MGZL that differ by clinical manifestation, response to chemotherapy, which emphasizes an importance of pathogenesis studying, and using of new therapeutic approaches.

Purpose. The identifying of the clinical, morphological, immunophenotypic and cytogenetic features of double-hit and double-expressor lymphomas as well as the development of optimal tactics of treatment and evaluation of efficiency of the ASCT were the main purposes of the study. Material and methods. The study included 85 patients: 45 males and 40 females, the median was 46,6 years (15-73). 62 patients with DLBCL and 23 with BCLu were given BL-M-04/ m-NHL-BFM-90 regimes in Hematological Scientific Center and Municipal Clinical Hospital №52, 2001-2015. Results. Stage I was diagnosed in 5 (6%) patients, II - in 13 (15%) patients, III - in 7 (8%) patients, IV - in 60 (71%) patients. Double-hit lymphoma was diagnosed in 6 (7%) patients (5 MYC+/BCL2+, 1 MYC+/BCL6+), single-hit lymphoma was diagnosed in 6 patients. The translocation was detected in 5 of 12 cases t(8;14)(q24;q32), in 1 case of 12 - t(2;8)(p21;q24), in 2 cases of 12 - t(8;22)(q24;q11) (restructuring c-MYC and IGL gene loci have been identified), in 3 cases of 12 - restructuring of c-MYC with non-IG partner [translocation was absent t(8;14)(q24;q32) and restructuring IGK and IGL gene loci], the partner was not identified in one case of translocation with c-MYC gene [restructuring c-MYC gene loci was identified and translocation was absent t(8;14(q24;q32)]. 8 factors had prognostic significance in relation to OS: nosology - BCLu vs DLBCL (p=0.007; RR=4.5), bone marrow lesion (p=0.0004; RR=7.9), B-symptoms (p=0.0002; RR=8.4), BCL2 expression (I=0.01; RR=4.4), MYC/BCL2 coexpression (p=0.017; RR=0.08), double-hit or double-expressor lymphomas (p=0.009; RR=15.1), the absence of rituximab in therapy (p=0.03; RR=0.3), unfulfillment of ASCT (p=0.003; RR=0.06). Two factors were significant in relation to probability of development of recurrence/progression: double-hit or double-expressor lymphomas (p=0.0005; RR=4.0) and IPI (p=0.03; RR=4.9). Conclusions. Thus, complex diagnostic includes the antibody to the BCL2 (clone 124, Dako) and MYC (clone Y69, Epitomics), and the conduct of standard cytogenetic analysis (SCA) and FISH to detect rearrangements of MYC, BCL2, and BCL6 genes in addition to standard immunohistochemical panel for aggressive B-cell lymphomas. It allows not only to establish the correct diagnosis (DLBCL, BCLu or LB), but also to detect the double-hit and double-expressor lymphomas, which require intensive induction with rituximab and high-consolidation ASCT in first remission.

to evaluate the efficiency of high-dose chemotherapy (HDCT) with further autologous blood stem cell transplantation (auto-BSCT) in the first-line therapy of patients with follicular lymphoma (FL) and poor prognostic factors.In 2000 to 2015, the National Research Center for Hematology, Ministry of Health of the Russian Federation, performed therapy in 39 patients with FL and poor prognostic factors (a total of 215 patients with FL). The R-CHOP treatment was done as induction therapy. Sequential HCT and further auto-BSCT were performed in 29 (74%) of the 39 patients, who had shown a partial tumor response to the induction therapy or achieved partial remission after 4-6 cycles of CT, but had poor prognostic factors. 22 of the 29 patients underwent auto-BSCT in first-line therapy after induction R-CHOP regimens. Among them, there were 17 men with a median age of 46 years (31-68 years). 21 of the 22 patients were recorded to have Stage IV by the Ann Arbor staging classification. Bulky peritoneal and retroperitoneal tumors larger than 7 cm were detectable at disease onset in 14 of the 22 cases. Two patients were noted to have phenomena of leukemization. 16 patients had bone marrow (BM) involvement. According to the Follicular Lymphoma International Prognostic Index-1 (FLIPI-1), the patients were divided into 3 groups: 1) a low risk (n=5); 2) an intermediate risk (n=3); a high risk (n=14). B-symptoms were observed in 16 cases. 16 patients were diagnosed with cytological grade I-II FL and 6 had grade IIIA. According to the tumor proliferative pattern, the distribution turned out to be as follows: nodular (n=6), nodular-diffuse (n=13), and diffuse (n=3). The proliferative activity index averaged 30% (8-90%). Serum and urine proteins were immmunochemically assayed in 18 cases, out of them 8 patients were diagnosed as having serum β2-microglobulin concentrations above normal as a poor prognostic factor. In 14 of the 22 patients, the activity of lactate dehydrogenase was greater than normal (266-7806 U/l).Out of the 22 patients, 20 who have undergone auto-BSCT in first-line therapy are survivors and have remission of the underlying disease: 18 and 2 patients achieved complete and partial remission, respectively. The follow-up period was 7 to 178 months (median, 32 months). After auto-BSCT in the first remission, 2 patients developed disease recurrences: an early recurrence after 9 months in one case and a late recurrence 6 years after completion of therapy in the other.The first prospective study of intensive therapy for FL in Russia has demonstrated that HDCT with further auto-BSCT in first-line therapy allows complete remission in patients with poor prognostic factors and higher overall and progression-free survival rates.Цель исследования. Оценить эффективность высокодозной химиотерапии (ХТ) с последующей трансплантацией аутологичных стволовых клеток крови (ауто-ТСКК) в терапии первой линии у больных с фолликулярной лимфомой (ФЛ) и факторами неблагоприятного прогноза. Материалы и методы. В период с 2000 по 2015 г. в ФГБУ Гематологический научный центр МЗ РФ проводилась терапия 39 пациентам с ФЛ и факторами неблагоприятного прогноза (всего 215 больных с ФЛ). В качестве индукционной терапии проведено лечение по программе R-CHOP. У 29 (74%) из 39 пациентов в случае частичного ответа опухоли на индукционную терапию или достижения частичной ремиссии после 4-6 курсов ХТ, но при наличии факторов неблагоприятного прогноза, выполнена последовательная высокодозная химиотерапия (ПВХТ) с последующей ауто-ТСКК. Из 29 больных ауто-ТСКК в терапии первой линии после индукционных режимов по программе R-CHOP выполнена 22 больным. Из них 17 мужчин с медианой возраста 46 (31-68) лет. У 21 из 22 больных констатирована IV стадия заболевания по классификации Ann Arbor. В 14 из 22 случаев в дебюте заболевания определялись опухолевые конгломераты более 7 см внутрибрюшной или забрюшинной локализаций (bulky). У 2 больных отмечались явления лейкемизации. У 16 пациентов имелось поражение костного мозга (КМ). По критериям FLIPI-1 пациентов разделили на 3 группы: в 1-й группе риска было 5 больных, во 2-й - 3, в 3-4-й - 14. В 16 случаях наблюдалось наличие В-симптомов. У 16 пациентов диагностирован I-II цитологический тип ФЛ, у 6 - IIIА. По характеру пролиферации опухоли распределение оказалось следующим: нодулярный у 6 больных, нодулярно-диффузный - у 13, диффузный - у 3. Индекс пролиферативной активности в среднем составил 30% (8-90%). Иммунохимическое исследование белков сыворотки крови и мочи проведено в 18 случаях, из них концентрация β2-микроглобулина в сыворотке выше нормы, как фактор неблагоприятного прогноза, диагностирована у 8 из 18 больных. Активность лактатдегидрогеназы превышала норму (266-7806 ед/л) у 14 из 22 пациентов. Результаты. Из 22 пациентов 20, перенесшие ауто-ТСКК в терапии первой линии, живы и находятся в ремиссии по основному заболеванию: полная ремиссия достигнута у 18, частичная - у 2. Период наблюдения составляет от 7 до 178 (медиана 32) мес. У 2 пациентов после ауто-ТСКК в первой ремиссии развились рецидивы заболевания: в одном случае - ранний спустя 9 мес, во втором случае - поздний спустя 6 лет от окончания терапии. Заключение. Результаты первого проспективного исследования интенсивной терапии у больных ФЛ в России демонстрируют, что ПВХТ с последующей ауто-ТСКК в терапии первой линии позволяет достичь полной ремиссии заболевания у пациентов с факторами неблагоприятного прогноза, а также увеличить общую и беспрогрессивную выживаемость.

The purpose of the study was to evaluate high-dose chemotherapy efficacy with the next autologous stem cells transplantation (ASCT) in first-line treatment of follicular lymphoma (FL) patients with unfavorable prognosis factors. 43 FL patients with unfavorable prognosis factors were observed in Hematological scientific center from 2000 to 2016. The patients received R-CHOP regime as induction therapy. ASCT in first-line treatment after inductional R-CHOP regimes was administrated in 23 patients. The results of the first prospective study of high-dose therapy in FL patients in Russia demonstrate that HDCT with followed ASCT in first line therapy allows to achieve complete remission in patients with unfavorable prognosis factors as well as to increase progression-free survival and overall surviva.

B-cell lymphoma that is unclassifiable and intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma (BL)--(UBL) is an aggressive lymphoma that has simultaneously morphological, immunophenotypical, and cytogenetic signs of both DLBCL and LB. At the same time due to its biological characteristics and clinical manifestations, UBL cannot be referred to as one of the above nosological entities. UBL has been first identified as an individual nosological entity in the 2008 World Health Organization classification. The review details the epidemiology, clinical manifestations, morphological pattern, immunophenotypic and karyotypic features, as well as therapeutic approaches and prognostic factors.В-клеточная лимфома неклассифицируемая, занимающая промежуточное положение между диффузной В-крупноклеточной лимфомой (ДВККЛ) и лимфомой Беркитта (ЛБ) - ВНЛ, является агрессивной лимфомой, имеющей одновременно морфологические, иммунофенотипические и цитогенетические признаки как ДВККЛ, так и ЛБ. В то же время по биологическим характеристикам и клиническим проявлениям ВНЛ не представляется возможным отнести ни к одной из указанных нозологий. ВНЛ впервые выделена как отдельная нозологическая форма в классификации Всемирной организации здравоохранения 2008 г. В обзоре подробно рассмотрены эпидемиология, клинические проявления, морфологическая картина, особенности иммунофенотипа и кариотипа, а также подходы к терапии и прогностические факторы.