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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.

Mantle cell lymphoma (MCL) is aggressive B-cell neoplasm diagnosed predominantly among older men. R-CHOP-like regimens allow to achieve high response rate, but the overall survival (OS) are disappointingly short - 3-4 years. An addition of high - dose cytarabine to the upfront therapy and autoSCT significantly improved outcomes but remain feasible largely for medically fit patients. Based on the activity and good tolerance of gemcitabine - oxaliplatin schemes in relapsed and refractory MCL patients, we developed an alternative first - line course for patients who are not eligible for R-HD-MTX-AraC.Assess toxicity and efficacy of R-DA-EPOCH/ R-HD-MTX-AraC and R-DA-EPOCH/R-GIDIOX schemes, autoSCT and R-maintenance in untreated MCL patients.47 untreated MCL patients from 6 centers were enrolled in prospective study between April 2008 and September 2013. All patients have stage II-V; ECOG 0-3; median age 55 years (29-64); Male/Female 76%/24%. MIPIb: 28% low, 33% intermediate and 39% high risk. Following 1st R-EPOCH patients were assigned to receive either R-DA-EPOCH/ R-HD-MTX-AraC or R-DA-EPOCH/ R-GIDIOX regimen. In the absence of renal failure, hematological toxicity grade 4 more than 3 days and severe infections patients received R-HD-MTX-AraC scheme (R 375 mg/m2 Day 0, Methotrexate 1000 mg/m2/24 hours Day 1, AraC 3000 mg/m2 q 12 hrs Days 2-3). Patients who had at least one of these complications received R-GIDIOX scheme (R 375 mg/m2 day 0, gemcitabine 800 mg/m2 days 1 and 4, ifosfamide 1000 mg/m2 days 1-5, dexamethasone 10 mg/m2 IV days 1-5, irinotecan 100 mg/m2 day 3, oxaliplatin 120 mg/m2 day 2). Subsequently these courses were alternating with R-DA-EPOCH in each arm of the protocol. Depending on the time of achieving CR patients received 6 or 8 courses, unless they progressed on therapy. Those patients who achieved PR/CR/CRu underwent autoSCT (BEAM-R). Post - transplant R-maintenance was administered for 3 years (R - 375 mg/m2 every 3 months).29/47 patients were treated on R-HD-MTX-AraC arm (median 50 years; MIPIb: 35.7% low, 28.6% intermediate, 35.7% high risk) and 18/47 patients were on R-GIDIOX arm (median 60 years; MIPIb: 16.7% low, 38.9% intermediate, 44.4% high risk). In R-HD-MTX-AraC arm CR rate was 96.5%. In R-GIDIOX arm OR and CR rates were 94.4% and 77.7% respectively. Main hematological toxicity of R-GIDIOX was leukopenia gr. 4 occurred in 74.1%. With median follow - up of 76 months, the estimated 7-years OS and EFS in R-HD-MTX-AraC arm are 76% and 57% respectively. In R-GIDIOX arm the estimated 7-years OS and EFS are 59% and 44%, respectively. There are no statistical differences in EFS (p=0.47) and OS (p=0.06) between two arms.The use of a risk - adapted strategy allowed 95.7% of patients achieve PR/CR/CRu, performed autoSCT and begun R-maintenance therapy with rituximab. None of the patients needed a premature discontinuation of therapy because of unacceptable toxicity. The performance of autoSCT and R-maintenance apparently allowed to partially offset differences in the intensity of induction therapy and to maintain comparable results of therapy in both induction arms.Лимфома из клеток мантийной зоны (ЛКМЗ) является агрессивной В-клеточной лимфомой, диагностируемой преимущественно у мужчин старшей возрастной группы. Применение R-CHOP-подобных схем позволяет у большинства больных достигнуть общий ответ (ОО), но медиана общей выживаемости (ОВ) составляет всего 3-4 года. Добавление к терапии высоких доз цитарабина и аутологичной трансплантации стволовых кроветворных клеток (аутоТСКК) увеличивают частоту достижения полных ремиссий (ПР) и продолжительность жизни, но только у соматически сохранных пациентов. Основываясь на высокой эффективности и безопасности гемцитабин - и оксалиплатинсодержащих схем в терапии рецидивов ЛКМЗ, мы предложили альтернативный курс терапии первой линии R-GIDIOX для пациентов, не являющихся кандидатами для применения высоких доз цитарабина и метотрексата (R-HD-MTX-AraC). Цель. Оценка эффективности и токсичности схем альтернирующей терапии R-DA-EPOCH/R-HD-MTX-AraC или R-DA-EPOCH/ R-GIDIOX, аутоТСКК и поддерживающей терапии ритуксимабом у вновь заболевших больных ЛКМЗ. Материалы и методы. В проспективное исследование с апреля 2008 по сентябрь 2013 г. включено 47 пациентов из 6 центров. Медиана возраста - 55 (29-64) лет, отношение мужчины/женщины - 76%/24%. Во всех случаях диагноз подтвержден выявлением t(11;14)(q13;q32); ECOG 0-3; распределение по MIPIb: 28% - низкий, 33% - промежуточный и 39% - высокий риск. В зависимости от переносимости первого курса терапии R-EPOCH пациенты рекрутировались в ветвь более интенсивной терапии R-DA-EPOCH/ R-HD-MTX-AraC или менее интенсивной терапии R-DA-EPOCH/R-GIDIOX. При отсутствии гематологической токсичности 4-й степени более 3 сут, серьезных инфекционных осложнений и признаков почечной недостаточности пациентам проводился курс R-HD-Met-AraC (R 375 мг/м2 в день 0, метотрексат 1000 мг/м2/24 ч в день 1, цитарабин 3000 мг/м2 2 раза в день в дни 2-3). При развитии одного из вышеперечисленных осложнений за первым курсом R-EPOCH следовал курс R-GIDIOX (R 375 мг/м2 в день 0, гемцитабин 800 мг/м2 в дни 1 и 4, ифосфамид 1000 мг/м2 в дни 1-5, дексаметазон 10 мг/м2 внутривенно в дни 1-5, иринотекан 100 мг/м2 в день 3, оксалиплатин 120 мг/м2 в день 2). Далее курсы полихимиотерапии (ПХТ) чередовались в каждом рукаве протокола. В зависимости от времени достижения ПР проводилось от 6 до 8 курсов терапии. При достижении частичной ремиссии (ЧР) и более выполнялась аутоТСКК (BEAM-R). Затем проводилась поддерживающая терапия ритуксимабом в дозе 375 мг/м2 1 раз в 3 мес в течение 3 лет. Результаты. Включено 29 из 47 пациентов в группу R-HD-MTX-AraC (медиана возраста 50 лет; MIPIb: 35,7% - низкий, 28,6% - промежуточный, 35,7% - высокий риск) и 18 из 47 - в группу R-GIDIOX (медиана возраста 60 лет; MIPIb: 16,7% - низкий, 38,9% - промежуточный, 44,4% - высокий риск). ПР в группе R-HD-MTX-AraC достигнута у 96,5%. Общий ответ и ПР в рукаве R-GIDIOX достигнуты в 94,4 и 77,7% соответственно. Лейкопения 4-й степени развилась после 74,1% курсов R-GIDIOX. Семилетняя ОВ и бессобытийная выживаемость (БСВ) в группе R-HD-MTX-AraC составили 76 и 57% соответственно, а в группе R-GIDIOX - 59 и 44% (при медиане наблюдения 76 мес). Сравниваемые группы статистически значимо не различались как по БСВ (p=0,47), так и по ОВ (p=0,36). Заключение. Применение риск - адаптированной стратегии позволило в 95,7% случаев достигнуть ответа на терапию, выполнить аутоТСКК и начать поддерживающую терапию ритуксимабом. Никому из больных не потребовалось преждевременного прекращения терапии из - за неприемлемой токсичности. Выполнение аутоТСКК и поддерживающей терапии ритуксимабом позволило частично нивелировать различия в интенсивности индукционной ПХТ и получить сопоставимые результаты лечения в обеих ветвях терапии.

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 evaluate late myelotoxicity (MT) relate to high-dose chemotherapy (CT) according to the modified NHL-BFM-90 (mNHL-BFM-90) program in adult patients with diffuse large B-cell lymphoma (DLBCL).The results of a complex clinical, laboratory, and instrumental examination, including cytologic, histologic, and routine cytogenetic studies of the bone marrow (BM), were analyzed in 40 DLBCL patients treated according to the mNHL-BFM-90 program in the National Research Center for Hematology (NRCH), Ministry of Health of the Russian Federation (MHRF), in 2002 to 2009; among them, there were 20 men and 20 women (median age, 57 years). A comparison group consisted of 19 patients who had received high-dose СНОР/R-СНОР-21 CT in HRC, MHRF, in the same period of time; out of them, there were 8 men and 11 women (median age, 70 years). The median posttherapy follow-up period was 6 years. The results of BM studies were analyzed before and 5-10 years after treatment in complete remission. The cytological and histological studies of BM determined its cellularity, the sizes of erythroid, granulocytic, and megakaryocytic lineages, their ratios, the signs of dysplasia, and stromal dysplastic changes. Routine BM cytogenetic study was conducted to identify karyological problems. Only myelopoietic changes that had been revealed for the first time 5-10 years after completion of CT were kept in mind as late MT. Cases of baseline and post-CT changes and those of baseline and no post-CT changes were not taken into account.Cytopenic syndromes (having no signs of myelopoietic lineage dysplasia or needing no blood component replacement transfusions) were revealed in 52% of the patients in the high-dose CT; thrombocytopenia amounted to 46%. In the late follow-up period, the patient group after high-dose mNHL-BFM-90 CT were found to have BM hypocellularity in 15 (38%) cases, a narrowing of erythroid and megakaryocytic lineages in 13 (33%) and 19 (48%) cases, respectively, and obvious secondary stromal changes in 17 (43%). The first 6 patients underwent routine BM cytogenetic study; all the patients were ascertained to have a normal karyotype; in this connection further BM study was stopped.The late MT of high-dose mNHL-BFM 90 CT is statistically significantly higher than that of the standard CHOP/R-CHOP-21 therapy. However, signs of myelodysplastic syndromes and those of cytopenia requiring blood component transfusions were observed in none patient.Цель исследования. Оценка отдаленной миелотоксичности (МТ) высокодозной химиотерапии (ХТ) по модифицированной программе NHL-BFM-90 у взрослых больных диффузной В-крупноклеточной лимфомой (ДВККЛ). Материалы и методы. Проанализированы результаты комплексного клинико-лабораторного и инструментального обследования, в том числе цитологического, гистологического и стандартного цитогенетического исследования костного мозга (КМ) 40 больных ДBККЛ, которым проведена высокодозная ХТ по программе mNHL-BFM-90 в ГНЦ МЗ РФ в период с 2002 по 2009 г., из них 20 мужчин, 20 женщин, медиана возраста 57 лет. Группу сравнения составили 19 пациентов, которым проведена ХТ по программе СНОР/R-СНОР-21 в ГНЦ МЗ РФ в тот же период, из них 8 мужчин и 11 женщин, медиана возраста 70 лет. Медиана срока наблюдения после окончания лечения 6 лет. Анализировали результаты исследования КМ до начала химиотерапии и через 5-10 лет после окончания лечения в полной ремиссии заболевания. При цитологическом и гистологическом исследовании определяли клеточность, величину эритроидного, гранулоцитарного и мегакариоцитарного ростков, их соотношение, наличие признаков дисплазии, диспластические изменения стромы. Выполняли стандартное цитогенетическое исследование КМ с целью выявления кариологических нарушений. В качестве отдаленной МТ учитывали только изменения миелопоэза, которые впервые выявлены через 5-10 лет после окончания ХТ. Случаи с исходно присутствующими и сохранившимися после ХТ изменениями миелопоэза, а также с исходно присутствующими и отсутствующими после ХТ не учитывали. Результаты. Цитопенические синдромы (без признаков дисплазии ростков миелопоэза и потребности в заместительных трансфузиях компонентов крови) выявлены у 52% больных группы высокодозной ХТ, 46% случаев из них составила тромбоцитопения. Из признаков отдаленной МТ в группе больных после высокодозной ХТ по программе mNHL-BFM-90 в отдаленном периоде наблюдений выявлены гипоклеточность КМ у 15 (38%) больных, сужение эритроидного и мегакариоцитарного ростков у 13 (33%) и 19 (48%) больных соответственно, выраженные вторичные изменения стромы у 17 (43%). Стандартное цитогенетическое исследование КМ выполнено первым 6 больным, у всех определялся нормальный кариотип, в связи с чем дальнейшее исследование КМ прекращено. Заключение. Отдаленная МТ высокодозной программы mNHL-BFM-90 статистически значимо превышает токсичность стандартной терапии СНОР/R-СНОР-21. Однако признаков миелодиспластических синдромов, а также цитопении, требующей трансфузий компонентов крови, ни у одного пациента не отмечено.

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 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.

Aim. To give the preliminary results of the AML-01.10 Russian multicenter randomized trial to treat adult acute myeloid leukemia (AML), the basic principle of which is to use high-dose anthracycline antibiotics in induction/consolidation. Subjects and methods. By December 2011, 145 patients with AML had been randomized from 18 hematology centers of 15 cities and towns of the Russian Federation; the median age of all the patients was 44 years. Seventy-one patients were analyzed in August 2011 (a 1.5-year follow-up). Results. The efficiency of 2 courses 7+3 using high-dose daunorubicin (60 mg/m2 per administration) and continuous infusion of cytarabine during the second course was high and comparable with that in the use of a high-dose HAM protocol as a second induction course and can achieve a complete remission in 74.6%. The protocol toxicity evaluated from its early mortality (11.3%) and its death in complete remission (16.6%) was permissible, particularly by taking into consideration the multicenter pattern of the trial. At the completion of analysis, 53 (68.8%) out of the 77 patients on whom the data on their vital status were available were alive. In this follow-up period, the frequency of recurrences was 19.2% (10/52). Only 3 (4.2%) patients out of the 71 patients in whom the efficiency of the protocol had been completely evaluated underwent allogeneic bone marrow transplantation. Conclusion. The total high dose (720 mg/m2) of anthracycline antibiotics, which is used in the period of induction and consolidation, determines the long periods of myelosuppression and intercourse intervals. Protocol deviations (no course of consolidation therapy, lower-dose idarubicin during consolidation therapy, a course of low-dose cytarabine between the courses of induction and consolidation chemotherapy, and very long intercourse intervals) were recorded in a total of 20 (28%) patients.

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.

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.

Double-hit (DH) lymphoma, an extremely aggressive variant of B-cell lymphoma, is accompanied by chromosomal abnormalities leading to the activation of a few oncogenes, one of which is the c-MYC gene in conjunction with BCL2 or BCL6 gene rearrangements. There are most common cases of MYC/8q24 and BCL2/18q21 gene rearrangements (MYC/BCL-2 DH lymphoma). The tumor is characterized by an aggressive clinical course and a poor response to chemotherapy (CT). The median survival in patients with DH lymphomas varies from 4.5 to 18 months. Such patients are generally resistant to CHOP-21 and R-CHOP-21 therapy regimens. For the treatment of patients with DH lymphoma, the Hematology Research Center, Ministry of Health of the Russian Federation, chose an original BL-M-04 polychemotherapy (PCT) protocol in combination with rituximab, followed by autologous stem cell transplantation (allo-SCT). The paper describes the experience in successfully treating a patient with two hematologic tumors: 1) MYC/BCL-2 DH lymphoma with high-dose PCT cycles, followed by allo-SCT, and 2) a metachronously developed second tumor (acute myelomonoblastic leukemia (AMML)) with CT cycles, followed by auto-SCT. The incidence of tumors induced by the previous high-dose CT for aggressive lymphomas for 10 years is 0.7 to 10%. As a rule, the development of secondary AMML is preceded by a history of myelodysplastic syndrome (MDS); characteristic chromosomal abnormalities (deletions of the long arm of chromosomes 5 and 7) are detectable. In this case, the follow-up was 3 months before the development of AMML, during this period the patient was not found to have laboratory signs of MDS (anemia, thrombocytopenia) or chromosomal abnormalities associated with secondary MDS/AML. The presence of a leukemic stem cell is associated with the occurrence and development of hemoblastosis; that of the similar cell populations that may cause B-cell lymphomas remains uncertain. The described case may have defect in a hematopoietic stem cell that gives rise to both germs of hematopoiesis, as well as complete donor chimerism of bone marrow hematopoiesis, which gives hope to long-term remission in both DH lymphoma and AMML.

To describe thrombosis of the sinus durae matris (TSDM) in lymphomas.402 patients with Hodgkin lymphoma were treated using the BEACOPP-14 protocol in 2006 to 2013. Thrombotic events occurred in 6% of the patients, including 3 (0.8%) who developed brain magnetic resonance imaging-verified TSDM.TSDM developed in 3 women aged 17, 18, and 25 years during 3-6 chemotherapy cycles involving glucocorticosteroids in a dose of 80 mg/m2 on days 1-7 and an oral contraceptive used continuously for 1.5-3 months. The symptoms of thrombosis were severe headache; 2 patients had convulsive syndrome with short-term loss of consciousness. Anticoagulant therapy with intravenous heparin 20,000--24,000 U/day led to thrombus recanalization within 4-10 days. No rethromoboses were observed during a subsequent follow-up.The BEACOPP-14 treatment in young women with Hodgkin lymphoma who continuously take oral contraceptives should be combined with anticoagulant therapy, by monitoring their coagulogram.

Myeloid sarcoma (MS) is a rare malignant solid tumor presented with myeloid blast cells showing varying degrees of maturation. MS may have an extramedullary site, precede, or develop simultaneously with the clinical manifestations of acute myeloid leukemia (AML); it may also occur as an AML relapse. Besides AML, MS may be a manifestation of chronic myeloid leukemia or other chronic myeloproliferative diseases. Due to the fact that this disease is rare, the bulk of the literature on MS is presented with single descriptions of retrospective studies and clinical cases. The paper describes 3 cases of MS with inversion of chromosome 16 and small bowel lesion.

To present the results of treatment in adult patients with acute T-lymphoblastic leukemia (T-ALL) according to the ALL-2009 protocol of the Russian Acute Leukemia Study Group, the basic principle of which is continuation of cytostatic treatment, early switch from prednisolone to dexamethasone, and long-term use of L-asparaginase.The results of diagnosis and treatment were analyzed in 70 patients with different immunological variants of T-ALL treated in the Russian multicenter trial.Out of the 70 patients with T-ALL, its early immunotype was determined in 32 (45.7%) cases, the thymic and mature immunotypes were found in 31 (44.3%) and 7 (10%) cases, respectively. The median age of the patients with T-ALL was 28 (ranged from 15 to 54) years; men were twice more than women (48 and 22, respectively). Bone marrow lesion was noted in all the patients with early T-ALL and in 80% of the patients with thymic and mature T-ALL. The enlarged mediastinum was significantly more frequently detected in mature T-ALL (100%) than in its early (53.4%) and thymic (60.7%) variants. Therapeutic effectiveness was evaluated in 58 patients. An analysis was made in January 2013. Induction therapy resulted in complete remission in 49 (84.5%) patients. The refractory course of the disease was recorded in 5 (8.6%) cases; early death was in 4 (6.9%). The rate of complete remission in thymic T-ALL, unlike in the early (72%) and mature (71.4%) variants, was significantly higher (100%) due to the absence of resistant forms and early mortality. Moreover, it should be noted that only the patients with early T-ALL (16%) died during the induction phase. In the patients with different variants of T-ALL, the overall and relapse-free survival rates were not significantly different, accounting for 67.2 and 76.2%, respectively. Multivariate analysis revealed no prognostically unfavorable factors that determined long-term results.The ALL-2009 protocol is reproducible in any regions of the Russian Federation and highly efficient in treating patients with T-ALL.

To make a differential diagnosis of diffuse large B-cell lymphoma (DLBCL) with primary involvement of the mediastinal lymph nodes (LN) and primary mediastinal large B-cell lymphoma (PMLBCL); to evaluate the efficiency of a modified NHL-BFM-90 (M-NHL-BFM-90) program in the treatment of the above nosological entities.The investigation enrolled 60 patients with large B-cell lymphoma (LBCL) with primary involvement of mediastinal LN who had been treated at the Hematology Research Center, Ministry of Health of Russia, in 2004 to 2012. The diagnosis of PMLBCL and DLBCL with primary involvement of mediastinal LN was based on histological findings, the phenotype of tumor cells, and molecular evidence. Treatment was performed according to the M-NHL-BFM-90 program. Three pregnant women received predelivery polychemotherapy (PCT) according to the VACOP-B protocol and continued to have a DexaBEAM chemotherapy regimen 3-4 weeks postpartum. In case of a residual mass, all the patients underwent consolidation radiotherapy to the mediastinal area in a total focal dose of 36 Gy.The diagnosis of PMLBCL was established in 39 patients: 10 men and 29 women whose ages were 18 to 60 years (median age 30 years); DLBCL with primary involvement of mediastinal LN was verified in 21 patients: 8 men and 13 women whose age was 21 to 70 years (median age 30 years). After m-NHL-BFM-90 treatment protocol, 5-year overall survival rates in the patients with DLBCL with primary involvement of mediastinal LN and in those with PMLBCL were 95+/-5 and 86+/-6% and 5-year event-free survival rates were 95+/-5 and 78+/-7%, respectively. All the pregnant women diagnosed with PMLBCL who had received the VACOP-B --delivery--Dexa-BEAM PCT regimen during pregnancy achieved remission. The follow-up periods were 30, 36, and 42 weeks.The patients with new-onset LBCL and primary involvement of mediastinal LN are a heterogeneous group that includes patients having two different diagnoses: PMLBCL and DLBCL. The efficiency of high-dose PCT is different in the patients with DLBCL with primary involvement of mediastinal LN and in those with PMLBCL (in spite of their similar clinical features, similar epidemiological characteristics, and the presence of the same unfavorable prognostic factors at onset).

To treat patients with different concurrent cancers, including lympho- and myeloproliferative neoplasms, is a difficult task. The paper presents the experience in successfully treating lymphogranulomatosis occurring in a female patient with chronic myeloid leukemia (CML). A combination of the BEACOPP-14 polychemotherapy regimen and imatinib induced no severe complications. Grade 2 neutropenia requiring no use of granulocyte colony-stimulating factors is the only manifestation of hematological toxicity. Infectious complications were successfully eliminated by first-line antimicrobial therapy in the intercourse periods. Remission in lymphogranulomatosis was achieved by polychemotherapy. The authors conclude that the chosen therapy option is effective and relatively safe in treating patients with CML concurrent with lymphogranulomatosis.

To analyze the causes of renal lesion in patients with Burkitt's lymphoma (BL) and to develop optimal treatment policy.The data of examination and treatment were analyzed in 20 patients with BL (14 men and 6 women aged 15 to 57 years (median age 24 years)) who had been followed up for renal lesion at the Hematology Research Center (HRC) in 2003 to 2011. When admitted to hospital, all the patients were found to have ureteric compression, renal parenchymal tumor infiltration, massive tumor cytolysis syndrome (MTCS). Polychemotherapy (PCT) was performed in accordance with the original intensive BL-M-04 protocol. The extent of the process was estimated according to the classification developed by S.B.Murphy: L3 variant B of acute lymphoblastic leukemia in 10 cases; Stage IV in 2; Stage III in 8. Acute renal failure (ARF) was identified in 13 patients. A control group comprised 36 patients with BL without ARF who had been followed up at the HRC in 2003 to 2011 and included into the BL-M-04 protocol. The ratio of patients with bone marrow lesion was 7:13 and 9:36 in the BL + ARF and BL-ARF groups, respectively.Decreased urine specific gravity and proteinuria (0.4 to 1.3 g/l) were the first manifestations of renal lesion and were seen in approximately 50% of all cases both on admission to hospital and in the first stages of PCT (10 and 9, 8 and 7 of the 20 cases, respectively). Microhematuria more commonly developed after initiation of PCT (7 and 3 of the 20 cases, respectively). ARF was diagnosed in 13 patients (24% of the 55 BL patients followed up at HRC in 2003 to 2011). One female patient developed ARF after the start of PCT. Twelve patients developed this condition at the onset of disease; in 4 patients, ARF existing prior to PCT began progressing after drug administration. The etiology of ARF was generally mixed. At the onset of disease, MTCS (n = 6) and specific renal parenchymal infiltration (n=6) were more common causes of ARF. Postrenal anuria was present in 2 cases. ARF after PCT initiation resulted from the toxic effects of methotrexate and MTCS (3 and 4 cases, respectively). ARF regressed in the early periods: in the prophase (n = 4) and during or the first PCT block A (n = 9). The BL patients with ARF, as compared to those without the latter, showed a statistically significant earlier onset of myelotoxic agranulocytosis (MTA): on day 3 of an intercourse interval (95 CI from 0 to 3 days) versus its day 5 (95% CI from 2 to 5 days) and a statistically significant longer duration of MTA--12 days (95% CI from 7 to 16 days) versus 7 days (95% Cl from 3 to 10 days); they were observed to have more severe mucositis. Despite the longer intercourse interval, 10 patients with ARF achieved remission; 4 patients died from therapy-refractory sepsis and 1 patient from thrombocytopenia. In the patients with ARF, mortality rates were significantly higher than in those without ARF (33% versus 10%; p = 0.04).Although there is a high risk of worsening renal dysfunction, PCT is a necessary condition for ARF resolution in BL.

To evaluate the efficiency of intensive polychemotherapy (PCT) in adult patients having diffuse large B-cell lymphoma (DLBL) of bones and soft tissues with and without poor prognostic factors (PPF).Out of 58 enrolled patients, 51 were diagnosed as having DLBL. Burkitt's lymphoma (BL) was diagnosed in 6 patients. One patient had marginal zone B-cell lymphoma. Thirty-five patients with DLBL (10 patients with PPF and 25 without PPF) and 3 patients with BL were treated with the CHOP/R-CHOP regimen. The NHL-BFM-90 program was used in 3 patients with BL and 16 with DLBL (15 patients with PPF and 1 patient without PPF).After radiotherapy, the patient with marginal zone B-cell lymphoma achieved a 20-month remission; three BL patients receiving CHOP died. All the BL patients receiving NHL-BFM-90 achieved complete remissions of 48 to 72 months. In 9 patients having DLBL without PPF, who received CHOP, five-year overall and event-free survival rates were 100%; in 22 patients with PPF, these were 50 and 45%, respectively. In the patients with and without PPF, who received CHOP/R-CHOP, the survival rates differed statistically significantly (p = 0.01; logrank test). In the group of 15 patients having DLBL with PPF, who were treated with the NHL-BFM-90 protocol, 14 achieved an average remission of 17 months. In the patients having DLBL with PPF who used NHF-BFM-90, therapeutic efficiency was significantly higher (p = 0.05; Fisher's exact test).Differential therapy for primary lymphomas of bones and soft tissues indicated that the NHL-BFM-90 protocol used in the PPF group was significantly more effective than the CHOP regimens.

To give data on the frequency of recurrent hairy cell leukemia (HCL) and to characterize the immediate and late results of its treatment in this group of patients.The data on the frequency of recurrences were analyzed in 165 patients with HCL after remission achieved by the purine analogue cladribin in the period 1995 to 2011. The treatment of recurrent HCL included splenectomy, interferon-a, cladribin, and rituximab.After a course of cladribin therapy, the total frequency of recurrent HCL was 22%. The high (47%) frequency of recurrences was found in young patients (less than 45 years) as compared to that (9%) in older patients. A combination of cladribin and rituximab showed a high efficacy in treating the early recurrence of HCL.The differences found in the frequency of recurrences give grounds to incorporate rituximab into the standard therapy regimen for HCL in young patients and in patients with early disease recurrence.

To define the efficiency of the GMALL 2002 program for the treatment of patients with T-cell lymphoblastic lymphomas (T-LBL).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.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%.The findings suggest that the GMALL 2002 programs are highly effective in treating patients with T-LBL at the first stage of treatment.

To review results of 2-year experience in execution of the protocol on the treatment of adult acute Ph-negative lymphoblastic leukemia ALL-2009.Of 111 patients registered in the study from November 2008 to December 2010 the analysis covered 96 patients from 23 hematological centers in 18 towns of the RF.Treatment according to the Protocol ALL-2009 resulted in achievement of a complete remission in 91.2% patients with low early lethality of 5.5%. Postremission lethality fell to 3.7% versus previous studies (22%). Overall 2-year survival and recurrence-free survival reached 77.6 and 78.4%, respectively. Detection of any chromosomic aberrations significantly affected recurrence-free survival: 74 vs 100% in patients with normal karyotype.Protocol All-2009 demonstrates high efficacy in moderate toxicity and good reproducibility in any hematologic center.

To diagnose diffuse large B-cell lymphosarcoma (DLBCLS) with primary involvement of the mediastinal lymph nodes (LN) and to evaluate the efficiency of aggressive polychemotherapy (PCT).The study included 15 patients (6 men and 9 women aged 18 to 70 years; median 38 years) followed up at the Hematology Research Center, Russian Academy of Medical Sciences, in 2004 to 2009. Three and 12 patients had Stages II and IE DLBCLS, respectively. B symptoms were found in 14 (93.4%) patients. Increased lactate dehydrogenase (LDH) concentrations were detectable in 14 (93.4%) patients; tumors of 10 cm or more (bulky disease) were seen in 11 (73.3%). Enlarged cervical, supraclavicular, and axillary lymph nodes were found in 9 (60%) patients; lung involvement via extension in 9 (60%), and invasion into the pericardium in 5 (33.3%) and soft tissues of the anterior thoracic wall in (13.3%). There were no signs of involvement of extranodal organs at the moment of diagnosis. All the 15 patients received PCT according to the modified NHL-BFM-90 program: 4 to 6 courses depending on the response to the therapy; 10 (66.6%) and 5 (33.3%) patients had 4 and 6 courses, respectively; for consolidating purpose, 11 (78.5%) patients were prescribed radiotherapy applied to the mediastinum in a cumulative dose of 36 Gy due to the fact that they had a residual mass.Thirteen (86.6%) patients achieved a complete remission (CR). Primary PCT resistance was confirmed in one case. Another patient was stated to have near-complete remission. No recurrences were notified during the follow-up. The mean CR duration was 24.5 (range 2-49) months.DLBCLS with primary LN involvement is an individual nosological entity to be differentiated from primary mediastinal large B-cell lymphosarcoma. In most cases, DLBCLS shows signs of a poor prognosis, which makes it necessary to perform aggressive PCT.

To evaluate efficacy of intensive modified program NHL-BFM-90 (mNHL-BFM-90) in adult poor-prognosis patients with diffuse large B-cell lymphosarcoma (DLBCL) of the bones and soft tissues.The mNHL-BFM-90 program was used in the treatment of 3 male and 2 female patients aged 17-69 years (median 42 years). Four patients had DLBCL of the bones and one patient--DLBCL of the soft tissues. All the patients had tumors more than 10 cm in size. B-symptoms, a high concentration of lactate dehydrogenase (LDG) were registered in 3 patients. One patient had stage IE by Ann-Arbor, two--stage IIE (involvement of regional lymph nodes), two--stage ME (multiple bone lesions). A total of 4-6 blocks of polychemotherapy according to mNHL-BFM-90 program were performed.Complete remissions were achieved in all the patients. They had no recurrences after 6 to 20 month (median 13 months) follow-up.Positive results of the program mNHL-BFM-90 in poor-prognosis patients with DLBCL of the bones and tissues necessitate further studies of this therapy.

To evaluate efficacy of the protocol NHL BFM-90 in the treatment of adult anaplastic large cell lymphosarcoma (ALCL) ALK+ and validity of addition of transplantation of autologous stem hemopoietic cells (ASHC) into first line treatment.We treated 13 patients with stage III-IV ALCL ALK+. The age of the patients ranged from 17 to 44 years (median 26 years). The diagnosis was made using morphological, histological, immunohistochemical methods with application of monoclonal antibodies to CD30, ALK, CD3, CD4, CD8, CD7, CD34, CD15, CD68, CD20, CD45RO, CD45RA. The patients were treated according to the protocol NHL BFM-90. ASHC was made in two patients with the disease stage IV.We obtained a complete remission in 12 of 13 patients, one woman died of infectious complications in the beginning of the treatment, one man had early recurrence 45 days after the end of the treatment with lethal outcome and disease progression. Two patients at stage IV and poor prognosis had undergone ASHC transplantation. They are now in remission for 5 and 12 months.ALCL ALK+ is characterized by an aggressive clinical course (11 of 13 patients had stage III-IV), high rate of extranodal lesions. Twelve patients achieved a complete remission, 11 (91.6%) of 12 patients are alive in observation median 27 months. We effectively used ASHC transplantation in the first-line treatment of 2 patients with stage IV of the disease and poor prognosis.

To compare efficacy of NHL-BFM-90 and CHOP-like courses in the treatment of anaplastic large cell lymphoma (ALCL).Twenty-two patients with ALCL participated in the study. The diagnosis was made basing on the findings of clinical, device, morphological, immunohistochemical and molecular-genetic examinations with application of a panel of monoclonal antibodies to CD30, ALK, CD3, CD4, CDS, CD7, CD34, CD15, CD68, CD20, CD45RO, CD45RA, Ki-67. 14 cases of 22 were negative by kinase of anaplastic lymphocytes (ALK-) and 8 were positive (ALK+). Mean age of ALK-ALCL patients was 39.6 +/- 4.1 years, of ALK+ALCL patients - 23.4 +/- 2.6 years. 14 patients were treated by the protocol NHL-BFM-90, 8 were initially treated with other schemes (CHOP, MACOP-B, BEACOPP and others). All 14 patients treated according to NHL-BFM-90 had ALCL stages III-IV with B-symptoms. 12 patients who completed treatment by the above protocol achieved complete remission after the forth course, 2 patients failed the treatment. Of 8 ALCL patients treated initially according to other schemes, a complete remission was achieved in 4 patients (2 had stage II). One of 4 patients with remission had recurrence. Four patients who had failed to achieve complete remission died of the disease progression.ALCL occurs more frequently in young and middle-aged patients. The disease has an aggressive course with rapid generalization. For such processes it is more preferable to use a modified protocol NHL-BFM-90.

To investigate characteristics of the course and efficacy of treatment of diffuse large B-cell lymphosarcoma (DLBL) with primary lesion of the spleen.From 1998 to 2006, primary splenic lesion was registered in 15 of 120 patients with DLBL and affected lymph nodes (LN), spleen and Waldeyer's ring. The diagnosis was made according to WHO criteria. Of them 14 patients had splenectomy as the first stage of therapy. The operation was followed with 6 to 8 courses of CHOP-21 (8 patients), 4 courses of R-CHOP-21 and radiotherapy (one patient). One patient received 7 courses of CHOP-21 followed by splenectomy. Because of the presence of several signs of unfavourable prognosis 5 patients under 60 years were given intensive therapy: 4-6 courses of the modified program NHL-BFM-90, 2 of 5 patients received radiotherapy.All the patients with primary DLBL of the spleen had two and more signs of unfavourable prognosis: elevated concentration of serum LDG, size of the tumor more than 10 cm, high proliferative activity of tumor cells, B-symptoms, severe condition. Seven patients had centroblastic, 8--anaplastic variants of DLBL. Tumor cells in primary DLBL of the spleen had no specific immunophenotype. Complete remission of the disease was achieved in 9 (90%) of 10 patients treated on programs CHOP-21, R-CHOP-21, in 4 of 4 patients on the modified program NHL-BFM-90. Mean follow-up was 39.3 months (from 7 to 103 months).For primary DLBL of the spleen characteristic are long-term remissions on first line therapy according to CHOP-21 program irrespective of morphology and immunophenotype.

To assess efficacy of a modified program NHL-BFM-90 in adult patients with primary diffuse large B-cell gastric lymphosarcoms (PDLBGL) with unfavourable prognosis.Modified courses of NHL-BFM-90 were conducted in 5 patients aged 27-67 years from January 2004 to September 2005. Four patients received chemotherapy of the first line, in one patient block therapy followed monotherapy with chlorambucil and a CHOEP course. All the patients were in a severe clinical condition and had several initial factors of unfavourable prognosis: size of the tumor more than 10 cm; stage IE and more advanced; B-symptoms; proliferative activity above 70%. The program NHL-BFM-90 was modified because of the patients' age. Chemotherapy was conducted according to the middle arm of the original program NHL-BFM-90, but methotrexate was introduced in a dose 1 g/m2 for 12 hours, while leukovorin was given 18 hours after the start of methotrexate injection. In two cases the blocks were enhanced with rituximab, 2 patients had doxorubicin in block A, in one case block C was enhanced with methotrexate. A total of 23 modified blocks NHL-BFM-90 were performed: one patient was given 6 blocks, two patients--5, one patient--4 blocks and one patient--3 blocks.Four patients after block 2 and one patient after block 3 of polychemotherapy NHL-BFM-90 achieved remission of the disease of 6 to 22 months duration which still continues. Infectious complications related to hematological toxicity arose more frequently at the latest courses of chemotherapy.Treatment according to the modified program NHL-BFM-90 in adult patients with PDLBGL and unfavourable prognosis is highly effective. For a mean follow-up of 10.2 months no recurrences occurred. The number of courses can be reduced to decrease accumulated hematological toxicity and in case of rapid achievement of remission.

To evaluate efficacy of treatment of primary mediastinal B-cell lymphosarcoma (PMBLS).Fifty nine patients with PMBLD were divided into three groups. Group 1 (n = 15) received 8 courses of CHOP, prevention of neuroleukemia and radiotherapy (RT). Group 2 (n = 8)--4 courses of ProMACE-CytaBOM or 1 course of MACOP-B, prevention of neuroleukemia and RT. Group 3 (n = 36)--2 courses of CHOP and 2-3 courses of ESHAP or 3 courses of DexaBEAM, surgical removal of residual mediastinal tumor (RMT), RT.The number of complete remissions in group 1 and 2 was the same (26 and 25%, respectively). Overall 5-year and event-free survivals in groups 1 and 2 were 52 +/- 5 and 13 +/- 5; 62 +/- 5 and 38 +/- 8%, respectively. In group 3 a complete remission was observed in 89% patients (p = 0.01), overall 5-year and event-free survival reached 88 +/- 8 and 85 +/- 7%, respectively. Removal of RMT in time of tumor size stabilization and partial remission (in 12 of 15 cases) led to a complete remission but in progression of the disease (in 3 cases) appeared ineffective. RT resulted in complete remission in 39 of 53 cases, stabilization of tumor growth was in 3 cases, progression--in 10, recurrence--in 1. RT was ineffective in all 4 cases of partial remission. RT use in stabilization of tumor size induced complete remission only in 1 of 7 cases.CHOP program is ineffective in PMBLS. Program ProMACE-CytaBOM or MACOP-B is insignificantly more effective than CHOP. Combined therapy is most effective. Surgery is justified in partial remission and tumor growth arrest. RT is indicated in complete remission to achieve its consolidation.

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).