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Background. In the superior vena cava syndrome, vein catheterisation provides an alternative for vascular access. Few reports describe the usage of femoral ports.Aim. Description of pros and contras for femoral port installation in patients with haematological malignancies and the superior vena cava syndrome.Materials and methods. This prospective non-randomised, single-centre study included 163 haematological patients implanted 72 ports in superior vena cava, 35 — in inferior vena cava and inserted with 156 non-tunnelled femoral catheters. Catheterisation properties, complications, duration of use and reasons for port and catheter removal were registered.Results. No significant differences were observed between ports in superior and inferior vena cava as per the frequency of urokinase use in catheter dysfunction, catheter dislocation, catheter-associated bloodstream and pocket infections. Differences were revealed in the catheter-associated thrombosis rate, which was higher with femoral access (17.0 % or 0.9/1000 catheter days vs. 8.3 % or 0.2/1000 catheter days, p = 0.017). Ports in inferior vena cava had a lesser duration of use than in superior vena cava (p = 0.0001). Unlike femoral ports, non-tunnelled femoral catheters had higher rates of catheter-associated thrombosis (9/1000 vs. 0.9/1000 catheter days, p = 0.002) and infection (4.9/1000 vs. 0.3/1000 catheter days, p = 0.002). One lymphoma therapy course required one femoral port or 1 to 14 (median 3) non-tunnelled femoral catheters.Conclusion. Femoral port implantation is a necessary measure in patients with the superior vena cava syndrome. It has advantages in terms of catheterisation frequency, lower infectious and thrombotic complication rates compared to non-tunnelled femoral catheters.

Background. Follicular lymphoma (FL) is the most common type of indolent lymphomas and accounts for 20–30 % of all non-Hodgkin’s lymphomas detected. High risk of recurrence and elderly patients make it difficult to choose induction therapy for FL. The R–B course in comparison with the R–CHOP course increases the progressive free survival (PFS) of FL patients and is less toxic. International studies have not studied the efficacy and toxicity of the R–B course due to various cytological types of FL. Aim of the study – assessment of the effectiveness and toxicity of the R–B course (with R support) in general and depending on the different cytological types of FL, the assessment of overall survival (OS) and PFS (adverse events: progression, relapse, death); identification of risk factors for an adverse event in general and death, in particular. The main endpoint of this study is selected BPV. Materials and methods. We performed a prospective, multicenter, open-label trial in Russia since June 1, 2013 till June 1, 2018. The study included 74 patients with FL. Median age of patients was 59 years (from 30 to 78 years). Treatment was completed in 66 patients, so this group of patients was analyzed. Ratio between men and women was 1:2. 32/66 of patients (48 %) were older than 60 years old. Patients received rituximab 375 mg/m2 on day 1 and bendamustine 90 mg/m2 on days 1 and 2 of a 4-week cycle (6 cycles). 49/66 (74 %) of patients were diagnosed with FL grade 1, 10/66 (15 %) – grade 2, 7/66 (11 %) – grade 3A. 34/66 (52 %) patients had nodular tumor growth type, 28/66 (42 %) – nodular-diffuse, 4/66 (6 %) – diffuse. High risk according to FLIPI had 25/59 (42 %) of patients with cytologic grade of FL 1–2 and 7/7 (100 %) of patients with FL grade 3A. Extranodal lesions were revealed in 26/66 (39 %) of cases: in 4/66 of cases – orbit, in 2/66 – parotid gland, in 5/66 – lungs, in 4/66 – intestines, in 2/66 – stomach, 2/66 – pancreas, 2/66 – uterus, 2/66 – skin, 1/66 – subcutaneous tissue, 3/66 – vertebrae, in 1/66 – latticed maze and nasal passages, 1/66 – kidneys, 1/66 – root of the tongue. In 23/26 (88 %) of cases extranodal lesion was revealed in generalized stage of FL (including lymph nodes and bone marrow). Extranodal lesions were found in 37 % of patients with FL grade 1–2, and 57 % with FL grade 3A. Bulky also was observed more frequently in pts with FL grade 3 3/7 (43 %) than in patients with FL grade 1–2 20/59 (34 %). (The risk factors of an adverse event are also its predictors in this study.) Results. Complete remission of disease was achieved in 40/66 (61 %) patients, partial remission – 13/66 (19 %) patients. Tumor progression observed in 11/66 (17 %) cases, patients were withdrawn from the protocol. А partial tumor response was achieved in 2/66 cases (3 %) and patients received high-dose therapy after 4 courses of R–B. Five-year (as well as the 3-year) overall survival (OS) of all patients (n = 66) in R–B was 90 % (95 % confidence interval (CI) 78–96), 5-year PFS – 70 % (95 % CI 55–85) and a 3-year PFS – 75 % (95 % CI 60–89). The cumulative incidence of relapse (considering competing risks of progression and death) at the 3th year after initiation of treatment was 11 % (95 % CI 3–19). The following independent statistically significant (p ≤0.05) predictors of PFS (measured in the onset of the disease) were determined (as a result of a stepwise multivariate cox regression analysis): 1) cytological type of tumor (only type 3A is significant); 2) involvement of nodal zones (more than 4); 3) presence of a conglomerate of tumor lymph nodes larger than 6 cm (bulky); 4) Ki-67 protein expression (more than 35 %). The first 3 characteristics (as well as the sign «presence of extranodal foci», close to the level of significance) are independent statistically significant predictors of OS. In the single factor analysis the following characteristics (besides the above) were significant: index FLIPI (significant only 5 points against all others), bone marrow damage, β2-microglobulin (more than 2.2 mg/L), age (over 68 years) and hemoglobin (less than 110 g/dL). Conclusion 1. The independent negative predictors of OS and PFS in follicular lymphoma were determined. 2. Of the predictors of an adverse event identified, the greatest risk (as a result of a multivariate analysis) is associated with a 3A cytological type of tumor. 3. The FLIPI index has a predictive value not only for the determination of OS, but also for the PFS (moreover, in reduced dichotomous form: 5 points against all the others combined). 4. An increase in the time interval between the first manifestations of follicular lymphoma (lymph node enlargement / appearance of a tumor formation) and the start of therapy beyond a certain threshold value (estimated to be approximately 22 months) is associated (according to the results of univariate analysis) with an increased risk of an adverse event. One of the reasons for the increase in this time interval is associated with expectant medical tactics adopted during the slow development of the clinical picture of the disease. The obtained result shows that the low rate of development of the clinical picture of the disease does not correlate with the low risk of adverse events, and, therefore, cannot be a determining factor when deciding whether to start treatment. 5. The morphology of the tumor is the determining factor in the choice of induction therapy. 6. After achieving full/partial remission of FL, there is a constant risk of recurrence of the disease (by the age of 3 from the termination of treatment, the risk is 11 % (95 % CI 3–19)). 7. The R–B course effectively sanitizes the bone marrow. 8. The R–B allows performing stem cells mobilization and autoSCT that is actual in FL patients with bone marrow involvement. 9. The treatment regimen of R–B is effective and has a relatively low toxicity, so it is advisable in the treatment of elderly patients.

Background. Extramediastinal and bone marrow involvement in PMBCL patients in the onset of the disease is an exception to the rules and complete information, except for the word “rare”, in Russian and international literature is not available. Objective : to characterize PMBCL patients with extramediastinal involvement. Materials and methods. From 2007 to 2017 diagnosis of PMBCL was established in 157 patients according to WHO criteria with extramediastinal involvement in 16 (10.2 %) patients, 3 of them were at different stages of pregnancy. The median age was 27 years (23–69). Patients received different therapy protocols: m-NHL-BFM-90, R-DA-EPOCH и VACOP-B. Results . One extramediastinal lesion was verified in 11/16 (68.7 %) patients, multiple – in 5/11 (31.3 %). The most common localizations were: pancreas – 6 (37.5 %), kidneys – 5 (31.2 %), ovaries – 3 (18.7 %), liver – 3 (18.7 %), bone marrow – 3 (18.7 %) and breast – 2 (12 %) cases. Involvement of stomach, bones, soft tissues, spleen, pelvis, adrenal gland was revealed in one case each. In 15/16 cases, extramediastinal lesions were combined with antero-superior mediastinum involvement and only in 1 cases an isolated lesion of the soft thorax tissues without involvement of mediastinal structures was revealed. Five-year overall survival in the group of patients with classical PMBCL who received R-DA-EPOCH, m-NHL-BFM-90 and cohort of patients with extramediastinal lesions was comparable and was 93 %. As a result of the analysis, in 10.2 % (16/157) of cases extramediastinal involvement was revealed. In all cases, there is involvement of organs and tissues, but not the lymph nodes. In 18.7 % (3/16) of cases there was bone marrow involvement, confirmed by molecular and histological studies. Conclusion. Involvement of the antero-superior mediastinum and the presence of extramediastinal lesion, bone marrow involvement is not excluding criterion for PMBCL, but requires differential diagnosis with DBCL, including standard and molecular methods. Is isolated extramediastinal involvement in PMBCL a poor prognostic factor, is uncertain because of the small number of observations.

To identify a parameter predicting a collection of at least 2·106 CD34+ hematopoietic stem cells (HSC)/kg body weight per leukapheresis (LA) procedure.The investigation included 189 patients with hematological malignancies and 3 HSC donors, who underwent mobilization of stem cells with their subsequent collection by LA. Absolute numbers of peripheral blood leukocytes and CD34+ cells before a LA procedure, as well as a number of CD34+ cells/kg body weight (BW) in the LA product stored on the same day were determined in each patient (donor).There was no correlation between the number of leukocytes and that of stored CD34+ cells/kg BW. There was a close correlation between the count of peripheral blood CD34+ cells prior to LA and that of collected CD34+ cells calculated with reference to kg BW.The optimal absolute blood CD34+ cell count was estimated to 20 per µl, at which a LA procedure makes it possible to collect 2·106 or more CD34+ cells/kg BW.Цель исследования. Выявление параметра, прогнозирующего сбор не менее 2·106 гемопоэтических стволовых клеток (ГСК) CD34+ на 1 кг массы тела (МТ) пациента за одну процедуру лейкафереза (ЛА). Материалы и методы. В исследование включили 189 пациентов с онкогематологическими заболеваниями и 3 доноров ГСК, которым проведена мобилизация стволовых клеток с последующим их сбором методом ЛА. У каждого пациента (донора) определяли абсолютное количество лейкоцитов и клеток CD34+ в периферической крови перед процедурой ЛА, а также количество клеток CD34+ на 1 кг МТ пациента в продукте ЛА, заготовленного в этот же день. Результаты. Корреляции между количеством лейкоцитов в крови и количеством заготовленных в продукте ЛА клеток CD34+ на 1 кг МТ не выявлено. Выявлена тесная корреляция между количеством клеток CD34+ в периферической крови до ЛА с количеством собранных ГСК, рассчитанных на МТ пациента. Заключение. Определено оптимальное абсолютное число клеток CD34+ в крови - 20 в 1 мкл, при котором за один ЛА возможно собрать 2·106 и более клеток CD34+ на 1 кг МТ.

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct type of large B-cell lymphoma. In this type of the disease, the neoplastic process is located in the anterior and superior mediastinum, frequently with compression of the superior vena cava and with tumor invasion into the adjacent organs and tissues: the pericardium, lung, pleura, etc. Despite the fact that in PMBCL progression, there may be involvement of extranodal organs, such as the kidney, adrenal glands, liver, and central nervous system, bone marrow (BM) injury is generally absent. Since BM injury in patients with diffuse large B-cell lymphoma is an independent poor prognostic indicator, there is reason to believe that BM involvement in PMBCL affects the prognosis. These cases may need intensified induction therapy followed by autologous hematopoietic stem cell transplantation; and BM injury should be monitored during the therapy. The paper gives reports of clinical cases of bone marrow involvement in 2 PMBCL patients treated at the National Research Center for Hematology, Ministry of Health of the Russian Federation.Первичная медиастинальная В-клеточная крупноклеточная лимфома (ПМВККЛ) является отдельной формой В-клеточной крупноклеточной лимфомы. При этой форме заболевания опухолевый процесс локализуется в переднем и верхнем средостении, нередко со сдавливанием верхней полой вены и прорастанием опухоли в прилежащие органы и ткани: в перикард, легкие, плевру и т.д. Несмотря на то что при прогрессии ПМВККЛ возможно вовлечение таких экстранодальных органов, как почки, надпочечники, печень и центральная нервная система, поражение костного мозга (КМ), как правило, отсутствует. Поскольку поражение КМ у больных ДВККЛ является независимым признаком неблагоприятного прогноза, есть основания предположить, что вовлечение КМ при ПМВККЛ влияет на прогноз. В подобных случаях, возможно, необходима интенсификация индукционной терапии с последующей трансплантацией аутологичных стволовых кроветворных клеток, а в ходе терапии следует проводить мониторинг поражения КМ. В статье представлены описания клинических случаев с поражением КМ у 2 больных ПМВККЛ в ФГБУ ГНЦ МЗ РФ.

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.

To characterize a group of patients with follicular lymphoma (FL) with leukemization and to evaluate the efficiency of different therapy options (R-CHOP/R-FMC/high-dose chemotherapy (HDCT)).18 (7.2%) out of 250 patients diagnosed with FL, who were examined and treated at the National Research Center for Hematology, Ministry of Health of the Russian Federation, were found to have leukemic FL (tumor cells in the peripheral blood smears were detected by cytology and flow cytofluorometry. Eight of the 18 patients had extranodal foci of involvement: lung, stomach, spleen, lumbar muscles, upper jaw, and vertebrae. Bone marrow was involved in 17 of the 18 patients. Tumor biopsy specimens displayed a morphological pattern of indolent FL in the majority of patients (10 of the 18 patients had cytological grade 1-2 tumors and 14 patients had a nodular or nodular-diffuse tumor growth pattern). The patients underwent R-CHOP/R-FMC) or HDCT cycles as first-line therapy, followed by autologous stem cell transplantation (auto-SCT).The median follow-up was 66 months (range 12-217 months). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 70% (10% SEM) and 35% (15% SEM), respectively. The median OS was not reached; the median PFS was 3 years.Leukemic FL is characterized by low OS and PFS rates. The most effective chemotherapy regimens were R-CHOP, followed by HDCT and auto-SCT in first remission or R-FMC. These cycles can to a greater extent achieve a complete eradication of the bone marrow tumor clone. Due to the relapsing course of FL and the aggressiveness of leukemic FL, it is expedient to carry out auto-SCT in first remission.Цель исследования. Охарактеризовать группу больных фолликулярной лимфомой (ФЛ) с лейкемизацией и оценить эффективность разных вариантов терапии (R-CHOP/R-FMC/высокодозной химиотерапии - ВХТ). Материалы и методы. Из 250 пациентов с диагнозом ФЛ, которые обследовались и получали терапию в ФГБУ ГНЦ МЗ РФ, у 18 (7,2%) выявлен лейкемический вариант ФЛ (обнаружены опухолевые клетки в мазках периферической крови цитологически и методом проточной цитофлюориметрии - ПЦФМ). У 8 из 18 пациентов определялись экстранодальные очаги поражения: вовлечение легких, желудка, селезенки, поясничных мышц, верхней челюсти, позвонков. В 17 из 18 случаев вовлечен костный мозг. Морфологически в биоптате опухолей у большинства пациентов отмечалась картина индолентной ФЛ (у 10 из 18 I-II цитологический тип опухоли, у 14 из 18 нодулярный и нодулярно-диффузный характер опухолевого роста). В качестве терапии первой линии пациентам проводились курсы R-CHOP/R-FMC или ВХТ с последующей трансплантацией аутологичных стволовых клеток крови (ауто-ТСКК). Результаты. Медиана наблюдения составила 66 мес (12-217 мес). Пятилетняя общая выживаемость (ОВ) и выживаемость без прогрессирования (БПВ) составили 70% (стандартная ошибка 10%) и 35% (15%) соответственно. Медиана общей продолжительности жизни не достигнута, медиана продолжительности жизни без прогрессирования составила 3 года. Заключение. Лейкемический вариант ФЛ характеризуется низкими ОВ и БПВ. Наиболее эффективными оказались следующие химиотерапевтические режимы: R-CHOP c последующей ВХТ и ауто-ТСКК в первой ремиссии или R-FMC. Данные курсы позволяют в большей степени добиться полной эрадикации опухолевого клона в костном мозге. В связи с рецидивирующим течением ФЛ, а также агрессивностью лейкемического варианта ФЛ в первой ремиссии целесообразно проводить ауто-ТСКК.

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.

to evaluate the efficiency of the R-DA-EPOCH-21 + R-DHAP protocol and autologous hematopoietic stem cell transplantation (a BEAM conditioning mode) in first-line therapy for primary mediastinal large B-cell lymphoma (PMBCL).In 2013 to 2016, the investigation enrolled 57 patients with newly diagnosed PMBCL (according to the 2008 WHO criteria). The results were analyzed in 40 patients who had completed their treatment.All the 40 patients (14 men and 26 women) (median age, 27 years (19 to 67 years)) received 6 cycles of polychemotherapy (PCT) in accordance with the R-DA-EPOCH-21 regimen. After induction PCT cycles, 32/40 (80%) patients achieved complete remission. Partial remission was stated in 8/40 (20%) patients who had further 2 cycles of chemotherapy using the R-DHAP program and autologous hematopoietic stem cell transplantation (a BEAM conditioning mode). Two-year overall and relapse-free survival rates were 100% and 96%, respectively; the median follow-up was 17 months.The R-DA-EPOCH regimen allows complete remission in 80% of the cases and two-year survival in 100%. If there are unfavorable factors at onset and in partial remission, it is appropriate to intensify treatment at early stages, by using high-dose chemotherapy and autologous hematopoietic stem transplantation.Цель исследования. Оценить эффективность протокола R-DA-EPOCH 21 + R-DHAP + трансплантация аутологичных гемопоэтических стволовых клеток крови (режим кондиционирования BEAM) в терапии первой линии при первичной медиастинальной В-крупноклеточной лимфоме (ПМВЛ). Материалы и методы. С 2013 по 2016 г. в исследование включили 57 больных с впервые установленным диагнозом ПМВЛ (согласно критериям ВОЗ, 2008 г.). Результаты проанализированы у 40 пациентов, завершивших лечение. Результаты. Всем 40 пациентам (14 мужчин и 26 женщин, медиана возраста 27 лет, от 19 до 67 лет) выполнили 6 циклов полихимиотерапии (ПХТ) по схеме R-DA-EPOCH-21. После индукционных курсов ПХТ полную ремиссию заболевания достигли 32/40 (80%) больных. Частичную ремиссию заболевания констатировали у 8/40 (20%) пациентов и в дальнейшем им выполнили 2 цикла химиотерапии по программе R-DHAP и трансплантацию аутологичных гемопоэтических стволовых клеток крови (режим кондиционирования ВЕАМ). Двухлетняя общая выживаемость и безрецидивная выживаемость составили 100 и 96% соответственно, медиана наблюдения 17 мес. Заключение. Выполнение схемы R-DA-EPOCH позволяет достигнуть полной ремиссии заболевания в 80% случаев и вероятность прожить 2 года 100%. При наличии факторов неблагоприятного прогноза в дебюте и достижении частичной ремиссии после индукционных курсов целесообразна интенсификация лечения на ранних этапах с использованием высокодозной химиотерапии и трансплантации аутологичных гемопоэтических стволовых клеток крови.

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 and toxicity of the intensive Burkitt's lymphoma (BL) therapy protocol BL-M-04.A total of 70 patients diagnosed with BL, including 45 men and 25 women whose age was 15 to 62 years (median age 31 years), were followed up in 2003 to 2014. Stage I (according to S. Murphy) was diagnosed in 4 (5.7%) patients; II in 9 (12.9%), III in 25 (35.7%), IV in 11 (15.7%), and Burkitt's leukemia in 21 (30%). There were tumor involvements of the bone marrow and central nervous system in 23 (32.9%) and 15 (21.4%) patients, respectively. B symptoms were detected in 56 (80%) patients; enhanced lactate dehydrogenase (LDH) activity was found in 50 (78.1%) out of 64 patients; moreover, in 34 (56.2%) out of 64 patients, LDH activity was more than twice as high as the reference values. The median LDH activity was 2398 (238-20,300) U/I. Acute renal failure at disease onset was identified in 17 (24.2%) patients; chemotherapy was initiated in 8 patients during renal replacement therapy. The treatment was performed using the BL-M-04±R protocol (4 successive blocks of A-C-A-C±R). Six blocks of A-C-A-C-A-C with rituximab has been carried out in patients with bone marrow involvement since 2011.Sixty-two (89%) patients achieved complete remission. At this time, 6 patients died from therapy complications during remission induction; 2 patients were observed to have disease progression; 3 developed disease recurrence (2 patients had early recurrence; 1 patient developed recurrence 2 years after treatment). Five-year overall survival (OS) was 85%; 5-year relapse-free survival (RFS) was 95%. The Cox multivariate regression analysis revealed that Burkitt's leukemia and bone marrow involvement were independent factors that influenced OS and RFS. The poor somatic status (3-4 ECOC scores versus 0-2 scores) proved to be statistically significant for OS rather than RFS.Despite the optimistic results obtained by our study group, there is a need to further improve BL treatment protocols and to elaborate novel approaches to therapy particularly for older patients and patients with Burkitt's leukemia.Лимфома Беркитта (ЛБ) является одной из наиболее агрессивных В-клеточных лимфом и характеризуется преимущественно экстранодальной локализацией опухоли, частым вовлечением в опухолевый процесс костного мозга (КМ) и центральной нервной системы (ЦНС). Отличительной чертой ЛБ является высокая пролиферативная активность опухолевых клеток (Ki-67 ~100%) и наличие перестройки гена c-MYC в область тяжелых или легких цепей иммуноглобулина. Цель исследования. Оценка эффективности и токсичности интенсивного протокола терапии лимфомы Беркитта ЛБ-М-04. Материалы и методы. С 2003 по 2014 г. наблюдали 70 больных с диагнозом ЛБ: 45 мужчин и 25 женщин в возрасте от 15 до 62 лет, медиана возраста 31 год. I стадия заболевания по S. Murphy диагностирована у 4 (5,7%) больных, II - у 9 (12,9%), III - у 25 (35,7%), IV - у 11 (15,7%), лейкоз Беркитта - у 21 (30%). У 23 (32,9%) пациентов отмечено вовлечение в опухолевый процесс костного мозга, у 15 (21,4%) больных - ЦНС. В-симптомы выявлялись у 56 (80%) пациентов, повышение активности лактатдегидрогеназы (ЛДГ) - у 50 (78,1%) из 64, при этом у 34 (56,2%) из 64 отмечено повышение активности ЛДГ более чем в 2 раза по сравнению с референсными значениями. Медиана активности ЛДГ составила 2398 (238-20 300) ед/л. Острая почечная недостаточность в дебюте заболевания определялась у 17 (24,2%) больных, у 8 химиотерапия начата на фоне терапии, замещающей функцию почек. Лечение проводили по протоколу ЛБ-М-04±R, (4 последовательных блока А-С-А-С±R). С 2011 г. больным с поражением КМ проводили 6 блоков А-С-А-С-А-С с ритуксимабом. Результаты. Полная ремиссия заболевания достигнута у 62 (89%) больных. При этом 6 пациентов умерли от осложнений терапии в период индукции ремиссии, у 2 наблюдалась прогрессия заболевания, у 3 развился рецидив заболевания (у 2 ранний, у 1 через 2 года после завершения лечения). 5-Летняя общая выживаемость (ОВ) составила 85%, 5-летняя безрецидивная выживаемость (БРВ) - 95%. При проведении многофакторного регрессионного анализа Кокса выявлено, что лейкоз Беркитта и поражение КМ являются независимыми факторами, влияющими на ОВ и БРВ. Плохой соматический статус (оценка по шкале ECOG 3-4 балла по сравнению с 0-2 баллами) оказался статистически значимым для ОВ, но не для БРВ. Заключение. Несмотря на оптимистичные результаты, полученные нашей исследовательской группой, необходимы дальнейшее совершенствование протоколов лечения ЛБ, разработка новых подходов к терапии, особенно у пациентов старшей возрастной группы, и больных лейкозом Беркитта.