Search

Aim. To assess the detection rate of human herpes virus DNA (of cytomegalovirus, herpes simplex virus types 1 and 2 [HSV-1/2], human herpes virus type 6 [HHV-6], and Epstein-Barr virus) in different biological environments at different stages of autologous hematopoietic stem cell transplantation (auto-HSCT) as well as the effect of immune factors on reactivation of viruses under study. Materials & Methods. From 2019 to 2021 the study enrolled 87 lymphoma patients during and after auto-HSCT. Virological monitoring was performed on biological fluids (blood, saliva, urine, etc.) prior to conditioning regimen on Day 0 as well as on Day +5 and Day +10 after auto-HSCT. On these days (Day 0, Day +5, and Day +10) the immune factors (IgM, IgG, and IgA levels and pattern of lymphocyte subpopulation in peripheral blood) in 15 % (14/87) of patients were assessed in terms of their effect on herpes virus reactivation. Results. The overall rate of viral DNA detection increased from 26 % (26/87) to 42 % (37/87) of cases in the period of granulocytopoietic recovery. The most frequent were HHV-6 and HSV-1/2 reactivations reported in 23 % (20/87) and 16 % (14/87) of cases, respectively. The median B-lymphocyte proportion in peripheral blood of patients with herpes virus reactivation was 0.26 %, whereas in patients without reactivation it was 6.7 % (p = 0.019). The median absolute B-lymphocyte count in the cohort of patients with detected viral DNAs was 0.001 x 109/L, whereas in patients without them it was 0.098 x 109/L (p = 0.026). Conclusion. A high rate of herpes virus DNA detection in lymphoma patients after auto-HSCT affected neither transplant engraftment nor transplantation mortality. Immune predictors of virus infection reactivation were the decreasing proportion of B-cells in the total lymphocyte count and the absolute B-lymphocyte count in the peripheral blood prior to auto-HSCT.

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.

Background. The management of aggressive lymphomas in pregnancy depends on the time of diagnosis and immu-nomorphological variant of tumor. The rarity of aggressive lymphomas in pregnant women, the absence of consistent approaches to the treatment of such patients, the lack of data on physical growth of children as well as the incidence of newborns’ congenital and acquired pathology make this subject of vital importance. Aim. To analyze the treatment results in patients with newly diagnosed aggressive lymphoma at different stages of pregnancy. Materials & Methods. From 1993 to 2020 at the National Research Center for Hematology 74 pregnant women with lymphomas were treated. Aggressive tumors were detected in 17 (23 %) of them: primary mediastinal (thymic) large B-cell lymphoma (п = 14), anaplastic large-cell lymphoma ALK+ (п = 1), high-grade B-cell lymphoma, unspecified (п = 1), and diffuse large B-cell lymphoma (п = 1). The median age of patients was 30 years (range 21-37 years). The median pregnancy stage on the diagnosis of aggressive lymphoma was 21 weeks (range 11-32 weeks). Results. In 1 case on the diagnosis of aggressive lymphoma at 11 weeks gestation dexamethasone 8 mg daily was administered up to the second trimester of pregnancy, afterwards the patient received polychemotherapy. On the diagnosis of aggressive lymphoma in the second (п = 13) and third (п = 2) trimesters of pregnancy the patients received polychemotherapy followed by delivery. In the third trimester of pregnancy delivery was performed with subsequent polychemotherapy in 1 patient. There were born 18 babies (1 pregnancy was multifetal): 8 girls and 10 boys. Conclusion. As a result of the chosen tactics and the work of interdisciplinary team of doctors all patients, who completed the treatment, are followed-up in complete remission. All born babies, despite chemotherapy and perinatal complications, are alive and develop without abnormalities.

Aim of the issue was to compare clinical characteristics and treatment results of patients with follicular lymphoma (FL) with translocations involving loci of c-MYC/8q24, BCL2/18q21 and/or BCL6/3q27 genes and patients with high - grade B-cell lymphoma [High - grade B-cell lymphoma (HGBL), double - hit (DH)]. Materials and methods. Since 2004 to 2017 years in National Research Center for Hematology 12 patients with high - grade B-cell lymphoma double - hit (HGBL DH) and 6 FL patients with translocations involving c-MYC and BCL2 and/or BCL6 had been treated. We performed a comparative analysis of clinical characterisctics in both groups. As primary endpoints was assessed frequency of complete remission (CR) or progressive disease (PD); as secondary endpoints - overall (OS) and event - free survival (EFS). Results. 5 patients with HGBL DH had c-MYC/BCL6, 7 - c-MYC/BCL2 rearrangements; 2 patients with FL had c-MYC/BCL2, 3 - c-MYC/BCL6, 1 - c-MYC/BCL2/BCL6 rearrangements. FL was represented by grade 3A in 2, grade 3B - in 4 cases, 3 of them had large - cell transformation. In HGBL DH and FL patients had no significant differences in clinical characteristics. The majority of patients had a widespread tumour, increased LDH activity, high frequency of extranodal and bone marrow involvement. Ki-67 expression level was lower in patients with FL (p.Цель работы: сопоставить клинические характеристики и результаты терапии больных фолликулярной лимфомой (ФЛ) с транслокациями с участием локусов генов с-MYC/8q24, BCL2/18q21 и/или BCL6/3q27 и больных В-клеточной лимфомой высокой степени злокачественности [high-grade B-cell lymphoma (HGBL)], double-hit (DH). Материалы и методы. С 2004 по 2017 г. в ФГБУ «НМИЦ гематологии» Минздрава России наблюдались 12 больных с диагнозом HGBL DH и 6 больных ФЛ с транслокациями с участием локусов генов c-MYC, BCL2 и/или BCL6. Мы выполнили сравнительный ретроспективный анализ клинических характеристик в обеих группах пациентов. В качестве первичных конечных точек оценена частота полных ремиссий (ПР) и прогрессирования заболевания (Прогр), в качестве вторичных - общая (ОВ) и бессобытийная выживаемость (БСВ). Результаты. У 5 больных с HGBL DH выявлены транслокации с участием локусов генов c-MYC/BCL6, у 7 - c-MYC/BCL2; у 2 с диагнозом ФЛ - c-MYC/BCL2, у 3 - c-MYC/BCL6, у 1 - c-MYC/BCL2/BCL6. Цитологический тип ФЛ представлен ФЛ 3А с бластоидной морфологической картиной в 2 случаях, ФЛ 3В в 4 случаях, 3 из которых имели признаки гистологической трансформации. Больные HGBL DH и ФЛ не имели значимых различий по клиническим характеристикам. Так, большинство из них имели распространенную стадию заболевания, повышенную активность лактатдегидрогеназы, высокую частоту вовлечения экстранодальных областей и костного мозга. Уровень пролиферативной активности Ki-67 был значимо выше у больных HGBL DH (p.

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.

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.