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Transcutaneous two-wave pulse oximetry is the most popular and prevalent method for studying blood oxygenation. However, during its implementation, smokers do not take into account the level of carboxyhemoglobin, which leads to an erroneous overestimation of hemoglobin saturation with oxygen. The computer program developed by us makes it possible, without the use of additional diagnostic equipment, to correct the results of monitoring blood oxygenation for the level of carboxyhemoglobin, correcting the indicated diagnostic inaccuracy in assessing the saturation of hemoglobin by oxygen in smokers.

to determine molecular diagnostics routine for different tissue samples in angioimmunoblastic T-cell lymphoma.Molecular studies were performed for 84 primary AITL patients. The median age was 61 year (29-81); the male to female ratio was 48/36. T-cell and B-cell clonality was assessed by GeneScan analysis of rearranged T-cell receptor (TCRG, TCRB) and immunoglobulin heavy chain genes. For the quantitative determination of cells with RHOA G17V mutation real - time polymerase chain reaction (PCR) with allele - specific LNA modified primers was used.In lymph nodes rearrangements of T-cell receptor genes were determined in 76 (90.5%) of 84 patients and were absent in 8 (9.5%) cases. Identification of the same clonal products of the TCRG and TCRB genes in the lymph node and in peripheral blood and/or bone marrow indicated the prevalence of the tumor process and was observed in 64.7% of patients. Clonal products in peripheral blood and/or bone marrow different from those in the lymph node indicated reactive cytotoxic lymphocyte population and were noted in 58.8% of AITL cases. Simultaneous detection of T- and B-cell clonality in the lymph node was observed in 20 (24.7%) of 81 patients. Cells with RHOA G17V mutation were detected in lymph node in 45 (54.9%) of 82 patients. The use of allele - specific PCR with LNA modified primers revealed presence of the tumor cells in peripheral blood in 100% and in bone marrow in 93.9% of patients with G17V RHOA mutation in the lymph nodes.The validity of different molecular assays performed on certain tissue samples for the diagnosis of angioimmunoblastic T-cell lymphoma has been evaluated. Quantitative allele - specific PCR assay for RHOA G17V mutation based on LNA modified primers possesses sufficient sensitivity for tumor process prevalence evaluation and minimal residual disease monitoring.Цель: определить показания и последовательность проведения молекулярных исследований при ангиоиммунобластной Т-клеточной лимфоме (АИТЛ) в различном биологическом материале. Материалы и методы. Молекулярные исследования проведены у 84 первичных больных АИТЛ. Медиана возраста составила 61 (29-81) год, соотношение мужчины/женщины - 48/36. Оценку T-клеточной и В-клеточной клональности проводили по реаранжировкам генов цепей T-клеточного рецептора и тяжелых цепей иммуноглобулинов. Для количественного определения клеток с мутацией G17V гена RHOA применяли полимеразную цепную реакцию (ПЦР) в реальном времени с аллель - специфичными LNA модифицированными праймерами. Результаты. В биоптатах лимфатических узлов реаранжировки генов цепей Т-клеточных рецепторов определены у 76 (90,5%) из 84 больных и отсутствовали в 8 (9,5%) случаях. Выявление одинаковых клональных продуктов амплификации генов TCRG и TCRB в биоптате лимфатического узла и в образцах периферической крови и/или костного мозга свидетельствовало о лейкемизации опухолевого процесса и наблюдалось у 64,7% больных. Определение в образцах периферической крови и/или костного мозга клональных продуктов, отсутствующих в лимфатическом узле, обусловлено реактивной цитотоксической популяцией лимфоцитов и наблюдалось в 58,8% случаев АИТЛ. Одновременное выявление Т- и В-клеточной клональности в биоптате лимфатического узла отмечалось у 20 (24,7%) из 81 больного. Клетки с мутацией G17V гена RHOA выявлены в биоптатах лимфоузлов у 45 (54,9%) из 82 пациентов. Применение метода аллель - специфичной ПЦР с LNA модифицированными праймерами позволило выявить лейкемизацию опухолевого процесса у 100% и поражение костного мозга - у 93,9% пациентов с выявленной мутацией в лимфоузлах. Заключение. В результате выполненной работы определены показания и последовательность проведения молекулярных исследований при АИТЛ в различном биологическом материале. Количественная аллель - специфичная ПЦР с LNA модифицированными праймерами для определения мутации G17V гена RHOA обладает высокой чувствительностью, позволяет верифицировать лейкемизацию опухолевого процесса и проводить мониторинг минимальной резидуальной болезни во время терапии.

Peripheral T-cell lymphomas (PTCL) are characterized by unfavorable prognosis and poorer survival in comparison with B-cell lymphomas. Probability of remission on first-line PTCL therapy is not higher than 60 % with high relapse rate. Longterm remission in PTCL relapses/progression cases typically fails to be achieved. The present article provides literature review and the authors’ own clinical experience in the management of anaplastic large-cell lymphoma, ALK-positive with primary skin and soft tissue lesions in an 65-year old female patient. After NHL-BFM-90 intensive chemotherapy the first 5,5-year complete remission was achieved in this patient. Afterwards a СНОР therapy-resistant relapse was identified. Chemotherapy-resistance of tumor was successfully overcome by adding of epigenetic drugs to cytostatic antitumor therapy. The duration of second complete remission is 3 years. Oncohematological diseases with either initial chemotherapy-resistance or the resistance acquired during antitumor therapy are most efficiently treated by various drug combinations including monoclonal antibodies, epigenetic drugs, and cytostatic therapy.

Background. Angioimmunoblastic T-cell lymphoma (AITL) is the rare lymphoproliferative disorder traditionally thought to be associated with EBV. This original study gives data about serological and molecular markers of herpes viruses in primary AITL patients. Materials and methods. The review includes analysis of clinical and laboratory features of 40 primary AITL patients. Peripheral blood, lymph node, bone marrow and bronco-alveolar aspirate samples were tested by ELISA, PCR and in situ hybridization. Results. Laboratory markers of the acute herpetic infection were detected in 29 (72.0%) out of 40 patients. Primary infection was detected in 8 cases: 6 - primary EBV, 1 - HCMV and 1-EBV and HCMV simultaneously. Anti-HSV 1,2 IgM were observed in 15 (37.5%) patients. EBV small non-coding RNAs (EBER) was positive in 27 (71.1%) out of 38 cases. The comparison of the detection of EBER and markers of acute EBV infection showed good correlation (p

Nodal anaplastic ALK-negative large cell lymphoma (nALCL, ALK-) is a Т-cell lymphoma that is characterized by aggressive clinical course and low sensitivity to СНОР (cyclophosphamide, doxorubicin, vincristine, prednisolone) and other chemotherapy regimen. In the article we present a literature review and describe our clinical case of nALCL, ALK-. For the first time a combination of Brentuximab vedotin with modified program NHL-BFM-90 was used as a first-line therapy. As a result of immunochemotherapy a complete antineoplastic effect was obtained. For consolidation of this effect high-dose chemotherapy with following autologous blood stem cell transplantation was performed. The chosen treatment tactics allowed to achieve a complete remission in a medium risk group patient.

Contex. Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of non-Hodgkins lymphoma, characterized by generalized lymphadenopathy, hepatosplenomegaly and dysproteinemia. Hypergammaglobulinaemia is revealed in 50-83% pts with AITL. However, the characteristics of immunoglobulinopathies observed in AITL are scarce. Objective: The aim of the study was to characterize quantitative and qualitative immunoglobulinopathies in patients with AITL at the onset of the disease. Patients and methods. 55 patients with newly diagnosed AITL were enrolled in the study, the male/female ratio was 30/25; median age was 61 (29-81) years. Diagnosis was based on standard WHO criteria. Immunochemical studies of blood serum included serum protein electrophoresis/immunofixation, nephelometric quantification of total immunoglobulins, serum free light chain assay. Results. Quantitative and qualitative immunoglobulinopathies were determined in 49 (89,1%) of 55 pts. Quantitative immunoglobulinopathies were revealed in 47 (85.5%) of 55 cases, qualitative - in 14 (25,5%). Combination quantitative and qualitative immunoglobulinopathies was observed in 12 (21,8%) of 55 pts. The detected immunoglobulinopathies were divided into 4 groups: polyclonal hypergammaglobulinaemia, hypogammaglobulinaemia, oligoclonal gammapathy, and monoclonal gammapathy. Polyclonal hypergammaglobulinaemia was marked in 41 (74.5%) of 55 pts, elevated level of IgG was determined in 27 (49,15%) of 55 cases, IgM - in 18 (32,7%) and IgA - in 21 (38.2%). Interestingly, polyclonal IgE hypergammaglobulinaemia was detected in 12 (48,0%) of 25 cases of performed studies. Hypogammaglobulinaemia was detected in 8 (14,5%) of 55 cases. Oligoclonal gammapathy was determined in 4 (7.3%) of 55 pts. Monoclonal gammapathy was revealed in 11 (20,0%) of 55 cases. The amount of monoclonal immunoglobulin varied from 2.6 to 14.1 g/l. Monoclonal immunoglobulin Gk was detected in 5 of 11 pts, Gλ - in 2, Mλ - in 2, Mk - in 2. Monoclonal gammapathy was accompanied by polyclonal hypergammaglobulinaemia in 9 of 11 cases, hypogammaglobulinaemia - in 2. Conclusions. Quantitative and qualitative immunoglobulinopathies are observed in most patients at the onset of AITL. Quantitative abnormalities were determined more often than qualitative. Monoclonal gammapathy can be a manifestation of lymphoproliferation and other concomitant disorders. The prognostic value of immunochemical parameters is still unclear and requires dynamic observation and study.

Background: Angioimmunoblast T-cell lymphoma (AITL) is a rare T-cell lymphoproliferative disease that is accompanied by generalized lymphadenopathy, hepatosplenomegaly, intoxication symptoms and extranodal lesions. The extranodal manifestations of the disease frequently involve various skin changes. One of the first such manifestations is maculopapular rashes observed in about half of AITL patients and usually preceding the appearance of lymphadenopathy. Other forms of skin lesions accompany the disease considerably less frequently.Aim: To characterize the range of skin changes in patients suffering from AITL, to establish a correspondence between the nature of skin changes and their histological picture.Materials and methods: 54 AITL patients were being treated at the National Research Centre for Hematology from 2000 to 2017, with the male/female ratio being 30/24. The median age was 61 (29–81) years.Results: Changes in the skin were observed in 24 (44.4 %) of 54 AITL patients, out of whom 18 (75 %) and 6 (25 %) were male and female patients, respectively. Maculopapular rash was observed in 22 (91.7 %) out of 24 patients. The morphological and molecular investigations of skin biopsy specimens exhibiting maculopapular rash demonstrated nonspecific reactive changes. Patients with maculopapular rash demonstrated an increase in the level of total (polyclonal) IgE. Specific skin lesions detected in 8 (14.8 %) cases were represented by a ‘livedo reticularis’, focal skin hyperpigmentation, erythroderma, left eyelid tumour and tumour in 3, 2, 1, 1 and 1 cases, respectively.Conclusion: Maculopapular rash frequently observed in AITL patients is a reactive process not associated with a specific skin lesion. Specific skin lesions in AITL are much less common and can be represented by various forms. In some AITL cases, skin changes of the reactive and tumour nature can be simultaneously observed.

Breast implant-associated anaplastic large-cell lymphoma will be identified as a separate nosological entity in the 2017 adapted WHO classification due to differences in its clinical presentations, pathogenesis, and prognosis with those of nodal and cutaneous anaplastic large-cell lymphomas. The paper gives a review of the literature and describes the authors' own clinical case of common breast implant-associated anaplastic large-cell lymphoma involving breast tissue, axillary lymph nodes, anterior chest muscles, and bone marrow. The treatment policy chosen by the authors could achieve complete remission.Ассоциированная с имплантатом анапластическая крупноклеточная лимфома молочной железы будет выделена в отдельную нозологическую единицу в адаптированной классификации ВОЗ от 2017 г. в связи с различиями клинической картины, патогенеза и прогноза с нодальной и кожной анапластическими крупноклеточными лимфомами. В статье представлен обзор литературы и описано собственное клиническое наблюдение распространенной ассоциированной с имплантатом анапластической крупноклеточной лимфомы, протекающей с поражением ткани молочной железы, подмышечных лимфатических узлов, мышц передней грудной стенки и костного мозга. Выбранная нами тактика лечения позволила достигнуть полной ремиссии заболевания.

Double-hit lymphoma (DHL) is a rare aggressive B-cell lymphoma with concomitant c-MYC, BCL2 or BCL6 gene rearrangements, which is characterized by the high frequency of extranodal lesions and by resistance to chemotherapy. The median survival does not exceed 18 months in patients with this disease. The majority of DHL is represented by с-MYC/BCL2 cases. The combination of c-MYC/BCL6 occurs rarely (5-8%). The paper describes a case of DHL with concomitant c-MYC and BCL6 gene rearrangements, which mimics diffuse large B-cell lymphoma, leg-type.'Double-hit' лимфома (DHL) - редкая агрессивная В-клеточная лимфатическая опухоль с сочетанной перестройкой генов с-MYC, BCL2 или BCL6, характеризующаяся высокой частотой экстранодальных поражений и резистентностью к химиотерапии. Медиана продолжительности жизни при данном заболевании не превышает 18 мес. Большинство DHL представлено случаями с-MYC/BCL2. Сочетание с-MYC/BCL6 встречается редко (5-8%). Представлен случай DHL-лимфомы с сочетанной реаранжировкой генов c-MYC и BCL6, протекающей под маской ДВККЛ leg-type.

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.

Aim. To define the efficiency of the GMALL 2002 program for the treatment of patients with T-cell lymphoblastic lymphomas (T-LBL). Subjects and methods. Twenty-five patients with a verified diagnosis of T-LBL were examined. Male/female ratio was 19:6; median age was 33 (range 16-67) years. There was a preponderance of patients with the generalized stages of the diseases: 2, 5, and 18 with Stages II, III, and IV, respectively. Mediastinal lesion was found in 20 (80%) of the 25 patients. Their treatment was performed according to the GMALL 2002 program and similar CHOP courses. Analysis was made in 2 groups that were not different in their clinical and morphological characteristics. Group 1 consisted of 17 of the 25 patients treated according to the GMALL programs; Group 2 comprised 8 patients who had similar CHOP and other chemotherapy regimens. Results. In Group 1, 15 (88%) patients achieved a complete clinical and hematological remission and 2 (12%) patients died in the first stages of the treatment. No relapses were noted. The median survival had not been achieved; 5-year overall survival was 88±8%. In Group 2, three patients were alive; 2 completed their treatment; 5 (63%) patients died from treatment failures. The median survival was 23±18%; 5-year overall survival was 45%. Conclusion. The findings suggest that the GMALL 2002 programs are highly effective in treating patients with T-LBL at the first stage of treatment.

Background: Primary mediastinal lymphoma (PML) is an aggressive, but curable disease. Given the rarity of disease there is no consensus on the most effective program. The most encouraging results with R-DA-EPOCH program (Dunleavy K. et al, 2013) demonstrated high response rate and improved long-term event-free (EFS) and overall survival (OS) without radiotherapy. However, in the real world setting we still face a very difficult treatment decision: on the one hand, due to increasing treatment-related toxicities about 20% of patients (pts) didn`t complete the treatment plan, on the other, approximately 10% of patients had disease progression or relapse. Based on our own successful experience of treating aggressive B-cell lymphomas by using the previously published R-m-NHL-BFM-90 protocol, we used a strategy of intensive induction of remission (blocks A, B), followed by de-escalation of therapy with 2 or 4 courses of R-EPOCH depending of interim PET/CT (iPET/CT) results. Here we report the first results of the toxicity and efficacy assessment of the response-adapted program R-m-NHL-BFM-90/R-EPOCH for patients with untreated primary mediastinal lymphoma. Methods: Eleven previously untreated patients (pts) with PML underwent R-m-NHL-BFM-90/R-EPOCH treatment between October 2004 and July 2015 in Federal State Budgetary Organization «National Research Center for Hematology of Russian Federation Ministry of Healthcare»; median age 34 years old (range 24-50); M\F=2\9; Ann Arbor stage >I in 11 (100%). All the patients had one or more adverse factors (bulky mediastinal disease>10 cm in 10 pts, soft tissues involvement in 7 pts, breast in 4 pts; elevated lactate dehydrogenase level in 7 pts, pleural effusion in 5 pts). The treatment plan consisted of: (i) pre-phase (dexamethasone and cyclophosphamide); (ii) induction of remission (courses A and B of NHL-BFM-90 program that was modified in the following way: the dose of methotrexate was reduced to 1500mg/m2 (12 h) in course A, doxorubicin in dose 50mg\m2 was added on the third day of course A); (iii) consolidation with R-EPOCH without dose escalation (2 courses in pts with negative iPET/CT (DS1-3) and 4 courses in pts with positive iPET/CT (DS 4-5)). Results: All the patients completed the treatment plan. Hematologic toxicity grade 3-4 was observed only during the induction therapy, mainly after block A. After the induction with R-m-NHL-BFM-90 8 out of 11 patients (72%) were iPET/CT-negative and received 2 additional courses of R-EPOCH; 3 out of 11 patients (28%) were iPET/CT-positive and received 4 additional courses of R-EPOCH. Only 1 patient`s response was assessed as DS4 at the end-of-treatment PET/CT. She received autologous transplantation of hematopoietic stem cells and has now been in complete remission for 12 months. With a median follow-up of 10 months (range 1-29) all the patients are alive in complete remission. Conclusions: Despite a small number of patients and a short follow-up period, our results suggest that the response-adapted strategy of treatment is a reasonable option for PML patients, even in high risk of treatment failure. Disclosures No relevant conflicts of interest to declare.

To study the clinical manifestations, diagnosis, and treatment of lymphoproliferative diseases (LPD) concurrent with tuberculosis.In 1990 to 2013, the Hematology Research Center, Ministry of Health of Russia, followed up 4422 patients with LPD. Lymphomas and leukemias were diagnosed using the universally protocols. Tuberculosis was verified by the results of a comprehensive examination involving the histological study of biopsy specimens.Tuberculosis was identified in 85 (2%) patients with LPD. According to the nosological entity, the tuberculosis detection rates were 3% (40/1350) in Hodgkin lymphoma (HL), 1.2% (20/1627) in aggressive lymphomas, 1.4% (16/1136) in mature cell lymphomas and chronic lymphocytic leukemia, and 2.9% (9/309) in hairy cell leukemia. In accordance with its site, pulmonary tuberculosis was 73%; extrapulmonary tuberculosis, 14%; generalized tuberculosis, 12%. In pulmonary tuberculosis, its disseminated and focal involvements were found in 71 and 18% of cases, respectively. Tuberculosis was detected in 43% of the patients with HL in remission; it occurred only in other hemoblastoses in its active phase. When tuberculosis and LPD were simultaneously found, both diseases were concurrently treated. If the chemotherapy of LPD was effective, tuberculosis was cured in all the patients.Patients with LPD are a group at increased risk for tuberculosis. The diagnosis of recurrent LPD must be histologically proven. When tuberculosis and LPD are simultaneously found, both diseases should be concurrently treated.

To assess the results of diagnosing and treating Pneumocystis pneumonia (PP) in patients with Hodgkin lymphoma (HL) over 15 years.In 1999 to 2013, PP occurred in 22 (3%) of 741 HL patients receiving programmed polychemotherapy (PCT). The male/female ratio was 1:1.1; median age was 32 (18-65) years. Advanced stages (IIB-IV) of the disease were seen in 82% of the patients. The diagnosis of PP was established when Pneumocystis (more than 5 cysts in the specimen) was detected in the lavage fluid by indirect immunofluorescence assay.PP developed after 4 or more cycles of PCT. Along with Pneumocystis, all the cases were found to have additional pathogens: herpes virus in 72% and bacteria and fungi in 33%. All the patients received combined antimicrobial therapy using high doses of intravenous trimethoprim-sulfamethoxazole. Ten (45%) patients required mechanical ventilation (MV). The total mortality in PP was 32% (7 patients died); moreover, none of the patients without MV died whereas the mortality among those who had MV was 70% (7 of the 10 patients died). High death rates (80%) were noted among the patients with recurrent and resistant HL.PP should be prevented with trimethoprim-sulfamethoxazole in patients with LH during PCT. If respiratory failure and X-ray signs of interstitial pneumonia appear, there is a need for fibrobronchoscopy with bronchoalveolar lavage and comprehensive microbiological testing of lavage fluid.

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.

To evaluate the efficiency of high-dose therapy according to the DLBL-CNS-2007 protocol in patients with testicular diffuse large B-cell lymphoma (DLBL).Out of 408 male patients with non-Hodgkin lymphoma, 8 patients aged 50 to 69 years (median age 55.5 years) with primary testicular (n=3) or with generalized-stage testicular DLBL (n=5) were included in the study. These patients were followed up at the Hematology Research Center, Ministry of Health of the Russian Federation, in 2007 to 2013. Systemic chemotherapy was performed in accordance with the DLBL-CNS-2007 protocol.The DLBL-CNS-2007 protocol was implemented in first-line therapy in 7 patients. At the first diagnostic stage, one patient was found to have anaplastic seminoma; in this connection right orchifuniculectomy was carried out, followed by radiotherapy applied to the scrotal region in a total focal dose of 34 Gy. This patient with disease recurrence was included in the DLBL-CNS-2007 treatment protocol. The number of polychemotherapy (PCT) cycles (n=4 or 6) was determined by the time to achieve complete remission. After completion of DLBL-CNS-2007 PCT, 6 patients achieved complete remission; the primary resistant disease was noted in 2 cases. At this moment 6 patients are alive in first complete remission during the median follow-up of 50 months (10-54 months).The findings suggest that high-dose therapy according to the DLBL-CNS-2007 protocol in patients with testicular DLBL can achieve complete remission and increase overall and event-free survival rates. This fact should be borne out by a large number of observations.

Infectious complications are one of the main causes of the lower efficiency of chemotherapy in hematologic oncology. The common infectious pathogens are herpes group viruses. The manifestations of herpesvirus infection or reactivation may be extremely diverse; just the same, digestive tract injury is rarely associated with herpesvirus infection in clinical practice. Viral mucosal injury of the intestine and pharynx is described in 2 patients with lymphomas during agranulocytosis. Virus-specific DNA was absent in blood; however, it was detected at high titers (the number of copies of 10(3) 10(5) genome-equivalent/mI) in feces and mucosal biopsy specimens. Addition of antiviral therapy could rapidly abolish infectious complications in both cases. Virological examination of material from the injury focus makes it possible to reveal a pathogenic virus even though the latter is undetectable in blood.

In the past decade, a notable advance has been made in the understanding of the pathogenesis of NK/T-cell lymphomas; however, their diagnosis remains difficult because of their rarity and clinical and morphological variabilities. The paper generalizes the ten-year experience of the Hematology Research Center, Ministry of Health of Russia, in diagnosing and treating hepatosplenic T-cell lymphoma (HSTL), considers the problems of differential diagnosis with other hematological diseases occurring with similar clinical and laboratory symptoms, and lays down current approaches to the diagnosis and treatment of this condition. A clinician's view of the problem of diagnosis and treatment of this disease is given. HSTL is shown to be a heterogeneous group of diseases differing in a T-cell receptor chain gene rearrangement, the clinical course of the disease, and overall survival (OS). According to our data, 3-year OS was 12%; the median survival was 26 months. Two-year OS for γδ and αβ HSTL was equal to 25 and 70%, respectively. The difference in OS for the variants of HSTL failed to reach statistical significance (because the sample might be insufficient).За последнее десятилетие достигнуты значительные успехи в понимании патогенеза NK/Т-клеточных лимфом, однако их диагностика остается затруднительной вследствие их редкости и клинико-морфологического разнообразия. В статье обобщен десятилетний опыт диагностики и лечения гепатолиенальной Т-клеточной лимфомы (ГЛТЛ) в ФГБУ 'Гематологический научный центр' Минздрава России, рассмотрены вопросы дифференциальной диагностики с другими гематологическими заболеваниями, протекающими со сходными клинико-лабораторными симптомами, сформулированы современные подходы к диагностике и лечению. Представлен взгляд клинициста на проблему диагностики и лечения данного заболевания. Показано, что ГЛТЛ - гетерогенная группа заболеваний, различающихся по реаранжировкам генов цепей Т-клеточного рецептора, клиническому течению заболевания, общей выживаемости (ОВ). По нашим данным, 3-летняя ОВ составила 12%, медиана продолжительности жизни - 26 мес. Для вариантов γδ и αβ ГЛТЛ 2-летняя ОВ равна 25 и 70% соответственно. Различие ОВ для вариантов ГЛТЛ не достигало статистической значимости (возможно, в силу недостаточного объема выборки).

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is a rare tumor derived from follicular T-helper and characterized by low response rate and relapsing course to standard therapy. CHOP-like therapy shows 70-80 % of overall response rate, though 2-year progression-free survival is observed only in 30-40 % of patients. Unsatisfactory results of treatment angioimmunoblastic T-cell lymphoma by ÑÍÎÐ-like therapy require searching new approaches to therapy. Aim: To define a rational approach to treatment of angioimmunoblastic T-cell lymphoma. Patients and methods: Ñlinical outcomes of 23 patients with newly diagnosed AITL treated between June 2002 and July 2015 we retrospectively analyzed. The diagnosis was verified according to WHO classification. Results: Among the 23 patients 14 men and 9 women were included with a median age of 63 (range, 29-81). Twenty-two of 23 patients had Ann Arbor stage IV. Bone marrow involvement was detected in 21 of 23 cases by histological investigation. Nine of 23 patients received CHOP-like therapy; other 14 patients were treated prolonged therapy. Eight (89%) of 9 patients after CHOP-like therapy had treatment failure. Time to disease progression ranged from 1 to 7 months (median 3). Fourteen of 23 patients were treated by prolonged therapy consisting of low dose cytotoxic drugs weekly and supporting the therapy by interferon-A and thalidomide. Supporting therapy has administrated after achieving complete remission and was continued in 2 years. Prolonged therapy wasn't finished in 3 patients with severe infections and somatic pathology. Eleven (79%) of 14 patients treated by prolonged therapy achieved complete remission, treatment was finished only in 5 of 11 patients; follow-up varies from 3 to 67 months, a median 29. Univariate analysis of progression-free survival curves showed that prolonged therapy is more effective than CHOP-like therapy (p < 0.01) (Fig.1). Prolonged therapy was performed in 4 of 8 patients with progression disease after CHOP-like therapy; 2 patients achieved a complete remission, continuing 41 and 77 months. Conclusion: Although, this was a small retrospective study, the results show that efficiency of prolonged therapy is better than CHOP-like therapy in patients withangioimmunoblastic T-cell lymphoma. Prolonged therapy allows preventing early treatment failures. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is a heterogeneous subgroup of PTCL with no consistent immunophenotypic, genetic and clinical features. PTCL-NOS represents less than 29% of all T-cell lymphomas in adults and often has an aggressive course with extranodal and systemic involvement. This study is focused on the application of clonality testing methods for PTCL-NOS diagnosis and monitoring. Patients and Methods: Biopsies, blood and bone marrow samples were tested for 30 patients with PTCL-NOS: the ratio of male/female was 15/15, median age was 56 years (32-75), and 22 of 30 patients had IV stage of the disease. TCRG and TCRB gene rearrangements were evaluated for T cell clonality analysis. We used PCR-based methods (BIOMED-2 standardized clonality protocol) followed by GeneScan analysis on the ABI PRISM 3130 Genetic Analyzer (Applied Biosystems). Results: Clonal TCR gene rearrangements were found in 29 of 30 patients (97%): TCRG in 27 of 30 (90%) and TCRB in 29 of 30 (97%). Primary biopsies or bone marrow samples showed oligoclonal pattern of rearrangements (more than 3 clonal peaks in TCRG or TCRB GeneScan profiles) in 13 of 30 patients (43%). New clonal rearrangements in affected tissues (skin, tonsil, CSF, lymph nodes and etc.) during disease progression were found in 15 of 24 (63%) patients. Various representations of clonal rearrangements in different tissues indicate the presence of several tumor clones in the majority of cases (19 of 30 patients; 63%). The presence of several clones correlated with the number of tissues examined (rs = 0.6, p Conclusion: Oligoclonality, clonal evolution and the appearance of new clones in the progression of the disease are typical features of PTCL-NOS. Multiple clonal rearrangements complicate diagnostics and assessment of minimal residual disease in this disease. Disclosures No relevant conflicts of interest to declare.

To compare programs of chemotherapy used in adult Berkitt-like lymphoma (ABLL); to assess efficacy and toxicity of the protocol AblL-M-04.31 ABLL patients (23 males, 8 females, mean age 27 years) participated in the study performed in Hematological Research Center in 1995-2004. ABLL stage I, II, III and IV was diagnosed in 3, 5, 8 and 15 patients, respectively. 10 patients had diffuse large B-cell lymphoma. 9 patients received 2 to 6 courses of CHOP, 1 patient--6 courses of Pro-Mace-Cytabom, 11 patients with newly diagnosed ABLL and 5 pretreated with CHOP--NHL-BFM-90. The modified protocol ABLL-M-04 of intensive short-term therapy included 10 patients, 2 of them pretreated.Of 10 patients given CHOP or CHOP-like courses 9 were resistant to therapy, 2 died of rapid progression, 7 were converted to the program therapy. 5 patients on the protocol NHL-BFM-90 died after short-term improvement. None of them achieved remission. Of 10 patients with newly diagnosed ABLL treated according to NHL-BFM-90 protocol, remission was achieved in 4 patients, follow-up median--34 months (2-56). Six patients died: 4 of progression, 2 of chemotherapy complications. BLL-M-04 therapy was made in 9 patients: 7 patients persisted on the first remission, 2 patients died of chemotherapy complications. Overall duration of the treatment was 3-3.5 months.The protocol ABLL-M-04 seems to be more effective than a classic NHL-BFM-90, but this must be supported by more cases. CHOP therapy cannot be recommended for patients with ABLL because of poor efficacy (all the CHOP patients died).

BACKGROUND: Follicular lymphoma (FL) is one of the most frequent types of B-cell lymphomas and accounts for about 22% of all non-Hodgkin lymphomas in Russia. The disease is usually a long-term condition with frequent relapse. At the same time 15-20% of pts have fast-tumor progression. Patients (pts) of this group die within the first 1.5-2 years from the time of diagnosis. High-dose chemotherapy (HDT) followed by ASCT in the presence of nonfavorable characteristics of FL (fast growth of tumor volume, B-symptoms, third citological grade of tumor, large tumor size, absence of anti-tumor response to R-CHOP courses in the first remission) increases the overall survival and progression-free survival of pts. AIM: To estimate HDT with ASCT efficiency among pts with FL in front-line therapy who received treatment in the National Research Center for Hematology during 2000-2013. PATIENTS AND METHODS: The results of ASCT among 12 pts with FL have been analyzed: 8 male and 4 female aged from 31 to 50 with median age 43. Patients in the main group (11/12) were on the IVth stage of tumor growth. In 6/12 cases the tumor size was more than 6 sm. Among 7/12 pts, besides lesions of lymphatic nodes, extra nodal lesions were found: infiltration in psoas (1/12), kidney (1/12), stomach (1/12), lungs (1/12), thyroid (1/12), pancreas (1/12). In 2/12 cases leukaemization was observed. Based on FLIPI criteria all the pts were divided into three groups: in the first risk group - 5/12 pts, in the second - 3/12, in the third - 4/12. B-symptoms were in the majority of cases (9/12). 9/12 pts were diagnosed with I-II cytological grade of FL, among 3/12 - III A/B. Based on the character of tumor growth the dispersion was the following: nodular tumor growth - 5/12, nodular-diffuse tumor growth-6/12, diffuse tumor growth - 1/12. Immuno-chemical investigation of protein serum and urine was performed in 9/12 cases, and among them rising serum β2-microglobulin above the norm was observed in 4/9 pts. A rise in lactate dehydrogenase concentration above the norm was observed among 4/12 pts. Lesion of bone marrow at the beginning of the disease was identified among half of the pts (6/12). Induction courses were performed on the R-CHOP programs, with intensive therapy - on protocol mNHL-BFM-90. RESULTS: Anthracycline courses were prescribed for nearly all of the pts as an inductive therapy: R-CHOP (11/12). mNHL-BFM-90 protocol was chosen as an inductive regime because of the fast growth of tumor size, IIIB grade of FL in 1/12 case. This tumor growth behaved like diffuse large B-cell lymphoma. In three cases medical-diagnostic splenectomy was undertaken before chemotherapy. After the inductive regimes the pts were given HDT based on the following scheme: two courses R-DHAP, course with rituximab and high-doses cyclophosphamide, a course with rituximab and high doses of etoposide, R-BEAM. All 12 pts, who were given ASCT are in full remission on the main disease. The period of observation is from 13 to 164 months. CONCLUSION: This first experience of intensive therapy in FL in Russia demonstrates that ASCT as a front-line therapy leads to complete remission of FL among pts who have nonfavorable prognosis factors. Disclosures No relevant conflicts of interest to declare.

Introduction: Peripheral T-cell lymphoma, unspecified (PTCL, NOS) is a tumor of mature T-lymphocytes characterized by aggressive course and low response rate to CHOP-like therapy. Bone marrow involvement in PTCL, NOS is detected by histological investigation in about 20-40% of patients and it is considered to be a poor prognostic factor. Importance of T-cell clonality examination in bone marrow as a prognostic and staging factor has been insufficiently studied. Aim: In order to evaluate the significance T-cell receptor gene γ- and β-chains (TCRG and TCRB) rearrangements for identification of bone marrow involvement; to estimate its value for staging and prognosis; to evaluate the significance of T-cell clonality persistence in bone marrow after initial therapy in patients with PTCL, NOS. Patients and methods: Bone marrow samples of 27 patients with primary PTCL, NOS (median age 62 years, range 32-77) have been obtained from 2006 till 2014 and were analyzed retrospectively. Morphological examination was performed for all bone marrow samples. Detection of T-cell clonality by revealing rearrangements of TCRB and TCRG were performed by PCR in bone marrow samples of patients before and after initial chemotherapy. Results: Bone marrow involvement was revealed by histological investigation in 22 (81%) of patients. T-cell clonality was detected by rearrangements of TCRG or TCRB in 26 (96%) patients, including 4 of 5 patients without bone marrow involvement by histology. Rearrangements of TCRG and TCRB were detected in 24 (89%) and 26 (96%) of patients, respectively. Rearrangements of TCRB were observed without rearrangements of TCRG in 2 cases. Interestingly, we detected more than 2 clonal rearrangements present simultaneously in 33% of cases. For monitoring minimal residual disease the examination of T-cell clonality in bone marrow samples was performed in 15 of 27 patients after initial therapy; all these 15 patients achieved complete remission. Persistence of T-cell clonality was observed in 14 of 15 patients after treatment, disease progression was noted in 1-3 months in all these cases. Conclusion: The examination of T-cell clonality in the bone marrow seems to be important and necessary for staging, monitoring minimal residual disease. Detection of T-cell clonality in bone marrow allows revealing its involvement even without morphological features in primary patients with PTCL, NOS. Persistence of clonal rearrangements in bone marrow after initial therapy shows continuing lesion and necessity for timely therapy escalation for patients with PTCL, NOS. Disclosures No relevant conflicts of interest to declare.