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Introduction. The formation of circulating autoantibodies capable of inhibiting factors of the blood coagulation system is accompanied by the occurrence of spontaneous and/or post-traumatic bleeding in patients without a history of previous disorders of the hemostasis system. One of the reasons for the development of such conditions is acquired hemophilia.Aim – to present algorithms for laboratory diagnosis of acquired hemophilia.Main findings. Primary diagnosis and control of therapy of the disease are carried out based on the results of coagulation studies, the decoding and interpretation of which often causes difficulties due to the low awareness of doctors about the algorithms for laboratory diagnosis and tactics for managing patients. In acquired hemophilia there is no direct relationship between the results of laboratory tests and the clinical manifestations of the disease, which is determined by the kinetics of the interaction of autoantibodies with blood coagulation factor (F) VIII. There is a «false» in vitro decrease in the activity of factors of the internal pathway (FIX, FXI and FXII), associated with the effect of a rapid inhibitor in high titers. An important laboratory task is the determination of lupus anticoagulant, which makes it difficult to timely diagnose and verify the diagnosis.

Introduction. Over the past 5 years, signifi cant progress has been achieved in the treatment of patients with Ph-negative acute lymphoblastic leukemia (ALL). Treatment results were compared between two protocols of the Russian multicenter studies «ALL-2009» and «ALL-2016», in which multicomponent high-dose consolidation was not used. The principle of continuity of treatment was observed with modifi cation of doses of cytostatic drugs depending on the depth of cytopenia.Aim – to compare the 5-year results of two studies and to determine the factors of unfavorable prognosis in the treatment of patients with ALL.Materials and methods. The studies were performed from April 2009 to April 2016 (ALL-2009) and from April 2016 to September 2021 (ALL-2016), and 596 patients were included: 330 in ALL-2009 and 266 in ALL-2016. The analysis was performed in March 2022. The median age of patients in ALL-2009 was 28 years (15–55), in ALL-2016 – 32.5 years (18–55). Cytogenetic studies were performed in 242 patients in ALL-2009 (73.3 %) and 236 patients in ALL-2016 (88.7 %). Patients in the ALL-2016 protocol underwent a centralized assessment of minimal residual disease (MRD) by fl ow cytometry on protocol +70 day (after completion of two induction phases), +133 and +190 days. Transplantation of allogeneic stem hematopoietic cells was performed in 7 % of patients in ALL-2009 and in 9 % in ALL-2016.Results. Overall, relapse-free survival (OS, RFS) and the probability of relapse for a period of 3 years from the moment of inclusion of patients in a particular study were 59 %, 63 % and 23 % for ALL-2009, and for ALL-2016 – 64 %, 59 % and 22 %, respectively. For patients with B-cell precursor ALL, two cytogenetic risk groups were formed, in which long-term survival rates differed signifi cantly: the standard group (hyperploid set of chromosomes and normal karyotype) – OS 63 %, RFS 70 %, and high cytogenetic risk (any abnormal karyotype, except for hyperploidy) – OS 49 %, RFS 52 % (р = 0.001, р = 0.0014). In T-ALL, cytogenetic markers had no prognostic value, but the immunophenotype of early T-cell precursor turned out to be an important predictor of poor prognosis (the probability of relapse was 52 % compared with 15 % for all other immunophenotypic variants). According to the results of centralized monitoring of MRD, it was determined that for B-cell precursor ALL, the signifi cant negative factors are the high cytogenetic risk group and positive MRD status at +70 day, and for T-cells, the early immunophenotype and positive MRD status at +133 day.

Introduction. The use of thrombopoietin receptor agonists, especially eltrombopag, in the treatment of aplastic anemia (AA) patients who did not respond to the previous immunosuppressive therapy (IST), is accompanied by the development of a hematological response in 40–60 % of patients.Aim — to study the effi cacy of using eltrombopag in treatment programs for AA patients refractory to previous IST.Methods. The study included 20 AA patients who were treated at the National Research Center for Hematology from 2015 to 2020. These patients did not respond to the conducted IST (ATG + CsA). Eltrombopag was administered at a dose of 150 mg/day. The results of treatment were assessed at 3 and 6 months: the achievement of hematological improvement, partial and complete remission, as well as the identifi cation of possible clonal evolution were determined.Results. Eleven out of 20 (55 %) patients responded to treatment: 2 patients developed hematological improvement, 6 patients — partial remission, 3 patients — complete remission. All 11 patients responded to treatment within 12 months from the start of eltrombopag, but further positive dynamics of hematological parameters are possible. The median duration of treatment with eltrombopag was 11 (1–48) months. Most of the patients were treated with eltrombopag in combination with CsA. The duration of the course of treatment with eltrombopag depended on the response received (stable hematological improvement, remission, as well as the detection of clonal evolution) or its absence and the need for ATG or BMT. An aberrant karyotype was found in 2 AA patients who received eltrombopag: in one patient monosomy of chromosome 7 was detected 1 month after the start of treatment, in another patient, 37 months later, a clone with a derivative of chromosome 16 from t(1;16) and subclone with complex disorders of the karyotype without signs of myelodysplasia in the bone marrow.Conclusion. The inclusion of the TPO receptor agonist eltrombopag in the treatment program for AA patients allows for a stable hematological response and remission of AA for patients who have not responded to IST. The effectiveness of eltrombopag is determined by adherence to the treatment algorithm, the optimal duration of the course, and the dose of the drug used. There is still a need for long-term observation of the patient and control morphological and cytogenetic studies.

Introduction. Pregnancy is one of the most frequent triggers of congenital and acquired forms of thrombotic thrombocytopenic purpura (TTP).Aim — to develop tactics for the treatment of pregnant women with TTP.Results. TTP was associated with pregnancy in 55.5 % of all cases of TTP in women. In 5 pregnancies in which the diagnosis of TTP was known before pregnancy, or established in the early stages, TTP was treated throughout the pregnancy. In the congenital form, plasma transfusions were performed once every two weeks until the 20th week of pregnancy, or weekly, if thrombocytopenia < 150 × 109 /L persisted. Plasma transfusions were performed weekly after the 20th week with the goal of achieving clinical remission. With acquired TTP, glucocorticosteroids and plasma exchanges were used as treatment, in 1 case — rituximab, with the aim of achieving a clinical remission and an ADAMTS13 activity > 20 %. In this group of pregnant women, 1 caesarean section was performed and there were 4 cases of vaginal deliveries, with a total of 5 children being born with an average Apgar score of 7.5. In 7 pregnancies in which TTP fi rst manifested late, leading to a delayed diagnosis, preventive and curative measures were not carried out before delivery. In this group there were 2 abortions of pregnancy, 5 surgical deliveries, 3 cases of preeclampsia, 3 acute cerebral circulatory disorders, 1 intraabdominal bleeding, 1 case of acute renal failure, with two women undergoing mechanical ventilation. There was 1 case of antenatal fetal death, with a total of 4 children being born, who were assessed on the Apgar scale with an average of 5 points.Conclusion. Timely diagnosis as well as ongoing therapeutic and preventive measures help to avoid complications during childbirth in pregnant women with TTP.

Background Myelodysplastic syndromes (MDS) can present a challenge for clinicians. Multicolor flow cytometry (MFC) can aid in establishing a diagnosis. The aim of this study was to determine the optimal MFC approach for MDS. Methods The study included 102 MDS (39 low-grade MDS), 83 cytopenic patients without myeloid neoplastic disorders (control group), and 35 healthy donors. Bone marrow was analyzed using a six-color MFC. Analysis was conducted according to the "Ogata score," "Wells score," and the integrated flow cytometry (iFC) score. Results The respective sensitivity and specificity values were 77.5% and 90.4% for the Ogata score, 79.4% and 81.9% for the Wells score, and 87.3% and 87.6% for the iFC score. Specificity was not 100% due to deviations of MFC parameters in the control group. Patients with paroxysmal nocturnal hemoglobinuria (PNH) had higher levels of CD34+ CD7+ myeloid cells than donors. Aplastic anemia and PNH were characterized by a high proportion of CD56+ cells among CD34+ precursors and neutrophils. The proportion of MDS-related features increased with the progression of MDS. The highest number of CD34+ blasts was found in MDS with excess blasts. MDS with isolated del(5q) was characterized by a high proportion of CD34+ CD7+ cells and low granularity of neutrophils. In 39 low-grade MDS, the sensitivities were 53.8%, 61.5%, and 71.8% for Ogata score, Wells score, and iFC, respectively. Conclusion The results support iFC as a useful diagnostic tool in MDS.

Reveal morphological and immunohistochemical predictors of reversibility of dialysis-dependent acute kidney injury (AKI) in patients with myeloma cast nephropathy (MCN) based on the study of kidney biopsy.Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission.Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively;p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively;p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN.If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.Цель.Выявить морфологические и иммуногистохимические предикторы обратимости острого повреждения почек (ОПП) с потребностью в диализе у больных миеломной каст-нефропатией (МКН) на основании исследования биоптатов почек. Материалы и методы.Проведено исследование нефробиоптатов 36 пациентов с МКН и 3-й стадией ОПП (AKIN, 2012) с потребностью в диализе. Исследование биоптатов выполняли полуколичественным и количественным методом с применением компьютерной морфометрии. Иммуногистохимически в клетках эпителия канальцев и интерстиции определяли экспрессию Е-кадгерина, виментина,-гладкомышечного актина. Индукционная терапия 26 пациентам проводилась по бортезомибсодержащим программам, 10 больным использовали другие схемы. Сравнительный анализ морфологических изменений в нефробиоптатах в зависимости от почечного ответа выполнен у пациентов с достигнутой гематологической ремиссией. Результаты.Улучшение функции почек наблюдалось только у пациентов с гематологическим ответом на терапию. Не выявлено различий в количестве склерозированных клубочков, белковых цилиндров, площади клеточной воспалительной инфильтрации, а также степени острого повреждения канальцев у пациентов с почечном ответом и без него. У больных с почечным ответом по сравнению с пациентами без улучшения функции почек площадь интерстициального фиброза меньше (соответственно 24,9 и 45,9%;р=0,001), а площадь экспрессии E-кадгерина больше (соответственно 15,9 и 7,1%;p=0,006). Фиброз интерстиция 40% и более и/или площадь экспрессии Е-кадгерина менее 10% от площади тубулоинтерстиция имеют неблагоприятное прогностическое значение в достижении почечного ответа при МКН. Заключение.При площади фиброза интерстиция 40% и более и площади экспрессии Е-кадгерина менее 10% вероятность отсутствия почечного ответа составляет 93,3% (отношение шансов 24,5) даже при достижении гематологического ответа на индукционную терапию. Количество белковых цилиндров, распространенность острого повреждения канальцев и воспалительной инфильтрации интерстиция не имеют прогностического значения.

To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with dialysis-dependent renal failure.During a period from May 2010 to December 2016 fourteen MM patients with dialysis-dependent renal failure aged 48 to 65 years underwent auto-HSCT. After the induction therapy complete response, very good partial response, partial response were documented in 64, 29, 7% of patients, respectively. In no case was a renal response achieved. Haematopoietic stem cell mobilization in most patients (13/14) was performed according to the scheme: G-CSF 10 g/kg. Melphalan in 3 dosages was used as pre-transplant conditioning: 100, 140 and 200 mg/m2; 13 patients underwent a single and in one case underwent a tandem auto-HSCT against the background of hemodialysis. Evaluation of the antitumor and renal response was assessed on the 100th day after auto-HSCT. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100200 mg/m2), 13 patients underwent a single and one patient underwent a tandem auto-HSCT. At +100 days after auto-HSCT, an antitumor response and renal response were assessed.The period of agranulocytosis after auto-HSCT was from 5 to 12 days (median 8,5) and was accompanied by infectious complications, cardiac and neurological dysfunctions. At +100 days after auto-HSCT, the complete response was confirmed in 71% patients and very good partial response was confirmed in 29% patients. The minimal renal response was registered in 2 patients (14%), hemodialysis was stopped. The transplant-related mortality was absent. After a median follow-up of 53 months 5-year progression-free survival was 59%, and overall survival was 93%.Carrying out auto-HSCT in patients with dialysis-dependent renal failure contributed to the achievement of a minimal renal response in 14% of cases, which allowed these patients to stop hemodialysis. Patients whose conditioning regimen was performed using melphalan at a dose of 200 mg/m2showed more frequent complications in the early post-transplant period compared to patients who received a lower dose of melphalan (100140 mg/m2). Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, which in some cases contributes to independence from hemodialysis.Цель.Оценить безопасность и эффективность трансплантации аутологичных стволовых клеток (ауто-ТГСК) крови больным множественной миеломой (ММ) с диализ-зависимой почечной недостаточностью (ПН). Материалы и методы.В ретроспективное исследование включены 14 больных ММ с диализ-зависимой ПН в возрасте от 48 до 65 лет, которым с мая 2010 по август 2018 г. выполнена ауто-ТГСК. После индукционного этапа лечения полная ремиссия, очень хорошая частичная ремиссия, частичная ремиссия документированы у 64, 29, 7% больных соответственно. Ни в одном случае почечный ответ не достигнут. Мобилизация стволовых кроветворных клеток у большинства больных (13/14) проводилась по схеме Г-КСФ 10 мкг/кг. В качестве предтрансплантационного кондиционирования использовался мелфалан в 3 дозировках: 100, 140 и 200 мг/м2; 13 больным выполнена однократная и в одном случае тандемная ауто-ТГСК на фоне программного гемодиализа. Оценка противоопухолевого и почечного ответа проводилась на 100-й день после ауто-ТГСК. Результаты.Период миелотоксического агранулоцитоза после ауто-ТГСК длился от 5 до 12 сут (медиана 8,5 дня) и сопровождался инфекционными эпизодами, кардиальной и неврологической дисфункциями. На +100-й день ауто-ТГСК полная ремиссия диагностирована в 71% случаев, очень хорошая частичная ремиссия у 29% больных. Почечный ответ зарегистрирован у 2 (14%) больных, программный гемодиализ им отменен и возобновления заместительной почечной терапии не потребовалось в течение 24100 мес после ауто-ТГСК. Летальность, связанная с трансплантацией, отсутствовала. При медиане наблюдения 53 мес 5-летняя выживаемость без прогрессии составила 59%, общая выживаемость 93%. Заключение.Проведение ауто-ТГСК больным с диализ-зависимой ПН способствовало достижению минимального почечного ответа в 14% случаев, что позволило прекратить выполнение гемодиализа этим пациентам. У больных, предтрансплантационное кондиционирование которым проведено с применением мелфалана в дозе 200 мг/м2, отмечены более частые осложнения в раннем посттрансплантационном периоде по сравнению с пациентами, получившими меньшую дозу мелфалана (100140 мг/м2). Ауто-ТГСК является эффективным методом лечения больных ММ с диализ-зависимой ПН, в ряде случаев способствующим достижению независимости от гемодиализа.

The properties of bone marrow-derived multipotent mesenchymal stromal cells (MSC) of patients with aplastic anemia at the onset of the disease are studied insufficiently. The aim of this work was to test the ability of MSC from patients with aplastic anemia to maintain hematopoietic precursors and to analyze the expression of genes associated with hematopoiesis and immune response. The ability of MSC to maintain hematopoietic precursors was determined by counting cobblestone area-forming cells; gene expression was analyzed by quantitative PCR. It was shown that MSC of patients with aplastic anemia preserve their ability to maintain hematopoietic precursors. Pronounced changes in the expression of the VEGFA and ANGPT1 genes were found. MSC from aplastic anemia patients with PNH clone significantly differ from those from aplastic anemia patients without PNH clone in terms of the expression of the SDF1, IL1R, and VEGFA genes. Changes in gene expression can be associated with the pathogenesis of the disease.

In chronic lymphocytic leukemia, the risk of second tumors including hematological malignancies, with which the use of purine nucleosides and alkylating agents in treatment of chronic lymphocytic leukemia is most often associated, is significantly increased. Concurrent detection of this disease and various hematological tumors is a rare occurrence in hematological practice. Use of cytogenetic method or analysis allows to differentiate between 2 tumors and confirm differences in genetic abnormalities in different clones and on different levels of cell differentiation. This article presents a clinical case of simultaneous chronic lymphocytic leukemia and myelodysplastic syndrome with 2 clones with different cytogenetic abnormalities: partial trisomy of chromosome 12 and deletion of the long arm of chromosome 5 formed at different levels of cell differentiation.

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

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

To estimate the number of early progenitors of bone marrow (BM) hematopoiesis in patients with diffuse large B-cell lymphoma (DLBCL) in the late period after high-dose chemotherapy (HDCT) according to the mNHL-BFM-90 program.The investigators analyzed the results of BM immunophenotypic and histological studies in 40 patients (median age, 57 years) with DLBCL who received HDCT according to the mNHL-BFM-90 program at the Hematology Research Center (HRC), Ministry of Health of the Russian Federation (MHRF), in the period 2002 to 2009. A comparison group consisted of 19 patients (median age, 70 years) treated according to the CHOP/R-CHOP program at HRC, MHRF, in the same period. The median follow-up period was 6 years. The results of BM examination were analyzed before and 5-10 years after the end of HDCT. Immunophenotypic study determined the number of early CD34+ hematopoietic progenitors. BM cellularity, the size of erythroid, granulocytic and megakaryocytic lineages, their ratio, the presence of dysplasia signs, and secondary stromal changes were histologically determined. The BM toxic injury signs found for the first time were evaluated as manifestations of late myelotoxicity.At 5-to-10-year follow-ups after the end of HDCT according to the mNHL-BFM-90 program, the patients showed a smaller number of early CD34+ progenitors of BM hematopoiesis in 31 (78%) cases than those treated according to the CHOP/R-CHOP-21 program (n=8 (2%)) (p=0.005). Myelopoiesis with decreased CD34+ cell count was characterized by hypocellularity in 8 (26%) patients (p=0.07), the narrowing of megakaryocytic lineage in 14 (45%) (p=0.006), erythroid one in 7 (23%) (p=0.01), and granulocytic one in 8 (26%) (p=0.92), pronounced secondary stromal changes in 15 (48%) (p=0.03), and grade 1 thrombocytopenia in 13 (42%); p=0.02).There is evidence that the number of early CD34+ progenitors of BM hematopoiesis decreased in patients with DLBCL in the late period after HDCT. The investigation shows the relationship of the reduction in the number of early CD34+ progenitors of BM hematopoiesis in the late follow-up period to the presence of pronounced secondary changes in the BM stroma (p=0.02). There was no statistically significant relationship of the decreased number of CD34+ cells to the age younger or older than 60 years, to the period after the end of chemotherapy, to gender or presence of specific BM injury.Цель исследования. Оценка количества ранних предшественников кроветворения в костном мозге (КМ) больных диффузной В-крупноклеточной лимфомой (ДВККЛ) в отдаленном периоде после высокодозной химиотерапии (ВДХТ) по программе mNHL-BFM-90. Материалы и методы. Проанализированы результаты иммунофенотипического и гистологического исследований КМ 40 больных ДBККЛ, которым выполнена ВДХТ по программе mNHL-BFM-90 в ГНЦ МЗ РФ в период с 2002 по 2009 г., медиана возраста 57 лет. Группу сравнения составили 19 пациентов, которым проведена терапия по программе СНОР/R-СНОР в ГНЦ МЗ РФ в тот же период, медиана возраста 70 лет. Медиана срока наблюдения после окончания лечения 6 лет. Анализировали результаты исследования КМ до начала ВДХТ и через 5-10 лет после окончания лечения. При иммунофенотипическом исследовании определяли количество ранних предшественников кроветворения CD34+. При гистологическом исследовании определяли клеточность КМ, величину эритроидного, гранулоцитарного и мегакариоцитарного ростков, их соотношение, наличие признаков дисплазии, а также вторичные изменения стромы. В качестве проявлений отдаленной миелотоксичности оценивали впервые выявленные признаки токсического поражения КМ. Результаты. У больных ДВККЛ после высокодозной терапии по программе mNHL-BFM-90 при сроке наблюдения от 5 до 10 лет после окончания химиотерапии выявлено снижение количества ранних предшественников кроветворения CD34+ в КМ в 31 (78%) случае, в отличие от 8 (42%) больных после терапии СНОР/R-СНОР-21 (р=0,005). Миелопоэз со сниженным количеством клеток CD34+ характеризовался гипоклеточностью у 8 (26%; р=0,07), сужением мегакариоцитарного ростка у 14 (45%; р=0,006), эритроидного у 7 (23%; р=0,01) и гранулоцитарного у 8 (26%; р=0,92), выраженными вторичными изменениями стромы у 15 (48%; р=0,03), тромбоцитопенией I степени у 13 (42%; р=0,02) больных. Заключение. Доказано уменьшение количества ранних предшественников кроветворения CD34+ в КМ у больных ДВККЛ в отдаленном периоде после ВДХТ. Показана зависимость снижения количества ранних предшественников кроветворения CD34+ в КМ в отдаленном периоде наблюдений от наличия выраженных вторичных изменений стромы КМ (р=0,02). Статистически значимой зависимости уменьшения количества клеток CD34+ от возраста моложе или старше 60 лет, срока после окончания химиотерапии, пола, наличия специфического поражения КМ не выявлено.Цель исследования. Оценка количества ранних предшественников кроветворения в костном мозге (КМ) больных диффузной В-крупноклеточной лимфомой (ДВККЛ) в отдаленном периоде после высокодозной химиотерапии (ВДХТ) по программе mNHL-BFM-90. Материалы и методы. Проанализированы результаты иммунофенотипического и гистологического исследований КМ 40 больных ДBККЛ, которым выполнена ВДХТ по программе mNHL-BFM-90 в ГНЦ МЗ РФ в период с 2002 по 2009 г., медиана возраста 57 лет. Группу сравнения составили 19 пациентов, которым проведена терапия по программе СНОР/R-СНОР в ГНЦ МЗ РФ в тот же период, медиана возраста 70 лет. Медиана срока наблюдения после окончания лечения 6 лет. Анализировали результаты исследования КМ до начала ВДХТ и через 5—10 лет после окончания лечения. При иммунофенотипическом исследовании определяли количество ранних предшественников кроветворения CD34+. При гистологическом исследовании определяли клеточность КМ, величину эритроидного, гранулоцитарного и мегакариоцитарного ростков, их соотношение, наличие признаков дисплазии, а также вторичные изменения стромы. В качестве проявлений отдаленной миелотоксичности оценивали впервые выявленные признаки токсического поражения КМ. Результаты. У больных ДВККЛ после высокодозной терапии по программе mNHL-BFM-90 при сроке наблюдения от 5 до 10 лет после окончания химиотерапии выявлено снижение количества ранних предшественников кроветворения CD34+ в КМ в 31 (78%) случае, в отличие от 8 (42%) больных после терапии СНОР/R-СНОР-21 (р=0,005). Миелопоэз со сниженным количеством клеток CD34+ характеризовался гипоклеточностью у 8 (26%; р=0,07), сужением мегакариоцитарного ростка у 14 (45%; р=0,006), эритроидного у 7 (23%; р=0,01) и гранулоцитарного у 8 (26%; р=0,92), выраженными вторичными изменениями стромы у 15 (48%; р=0,03), тромбоцитопенией I степени у 13 (42%; р=0,02) больных. Заключение. Доказано уменьшение количества ранних предшественников кроветворения CD34+ в КМ у больных ДВККЛ в отдаленном периоде после ВДХТ. Показана зависимость снижения количества ранних предшественников кроветворения CD34+ в КМ в отдаленном периоде наблюдений от наличия выраженных вторичных изменений стромы КМ (р=0,02). Статистически значимой зависимости уменьшения количества клеток CD34+ от возраста моложе или старше 60 лет, срока после окончания химиотерапии, пола, наличия специфического поражения КМ не выявлено.

Introduction: Myeloma cast nephropathy (MCN) is a main cause of acute kidney injury (AKI) at multiple myeloma (MM) onset. Wherein 5-9% of newly diagnosed MM patients are dialysis dependent. The introduction of novel agents has provided the achievement of rapid and deep hematologic response in most patients. However, the renal response in patients on dialysis is only 38-62.5%. The predictors of AKI reversibility in patients with MCN remain not enough studied. Aim: to determine clinical, morphological and immunohistochemical predictors of reversibility dialysis dependent AKI in patients with MCN. Materials and methods: 36 patients aged 38 to 74 years (median age=57 years) with newly diagnosed MM and dialysis dependent AKI stage 3 (AKIN, 2012) due to MCN were enrolled into the study from January 2006 till November 2019. The diagnosis of MM, hematologic and renal response were established according to the 2016 IMWG criteria. MCN was determined by renal biopsy performed prior to induction therapy. The assessment degree of acute tubular injury, tubular atrophy and interstitial fibrosis (IF/TA) were semi-quantitatively evaluated. The number of sclerotic glomerular were calculated manually. The median number of casts was defined by all casts in a section divided by number of fields observed (х100). Additionally, square of interstitial fibrosis, interstitial inflammation, expression of Immunohistochemical markers (E-cadherin, α-smooth muscle actin (α-SMA), vimentin) were measured by computerized quantitatively image analysis using the digital module Leica (Germany). The time from diagnosis of AKI to start of induction therapy did not exceed 3 months. Bortezomib based first line treatment regimen was used in 25 (69%) of patients; 9 (25%) patients received chemotherapeutic agents only, 2 (6%) dead before a start of induction therapy. Statistical software package SAS 9.4 was applied for calculations. Overall survival according to renal response was compared by using Kaplan-Meier curves. Also frequency, logistic, discriminant and ROC analysis were used. All estimates are shown with a 95%CI. Results: Hematologic partial response or better occurred in 19 (53%) of patients, median of 32 (13-129) days. Renal response - in 14 (39%). In 3 (8%) cases renal function improved after correction of dehydration before start of antimyeloma therapy, in the remaining 11 (30%) patients only when hematologic response was achieved (p = 0.001). The frequency of renal response was depending on start of antimyeloma therapy before and after 4 weeks from diagnosis of AKI and was 83% and 17%, respectively (p Patients with hematologic response were divided into two groups (Tab.). The main pathological findings associated with renal response were less frequent mild to severe IF/TA in patients with and without renal response (moderate 45% vs 75%, respectively, p=0.008), less area of interstitial fibrosis (24.9% vs 44.7%, respectively, p=0.001), percentage of proximal tubules with save epithelial phenotype and less area of expression E-cadherin at interstitium (15.9% vs 7.1%, respectively, p=0.006). The median number of casts per field was the same (6.4 and 6.3, p=0.64) as well as the percentage of tubule lumen obstruction by casts (13.6% and 15.1%, p=0.81). Statistically significant correlation between the expression area of E-cadherin and interstitial fibrosis was not found (Rs= -0.335, p= 0.065). Therefore, a combination of these factors can be used to predict renal response in the onset of AKI due to MCN (area under the ROC curve is 0.84). The prognostic model and logical rule allow to define groups of renal outcomes (Fig.). If expression area of E-cadherin is less than 10% and / or area of interstitial fibrosis is more than 40% of the interstitium, a renal response is unlikely (OR = 24.5) and will not be achieved in almost 90% of cases, despite hematological response. Discussion. Reversibility of dialysis dependent AKI due to MCN rely on the achievement of hematological response and the time from diagnosis of AKI to start of antimyeloma therapy. There are predictors of renal response of these patients determined by the severity of morphological changes: degree of IFTA, quantitative area of interstitial fibrosis and E-cadherin expression. Disclosures No relevant conflicts of interest to declare.

We measured specific volume and hematocrit of blood clots prepared from the whole blood of patients with hemophilia A and healthy male volunteers. It was shown that in the hematocrit range of 43.5-52.5%, specific volume of the blood clot in hemophilia patients with low level of factor VIII (1-4%) was higher than in volunteers. After injection of factor VIII, specific volume of blood clots in hemophilia patients decreased. Hematocrit of the blood clots derived from the whole blood linearly depended on the mean erythrocyte density in both volunteers (r=-0.74, p=0.01) and patients with factor VIII level of 1-4% (r=-0.95, p

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.

Aim. To generalize hematologists’ experience of the diagnosis and differential diagnosis of splenic red pulp lymphoma (SRPL). Materials and methods. Eighty-seven splenic biopsy specimens taken from patients with different B-cell lymphoproliferative diseases were examined in the Hematology Research Center in 2013—2014. The diagnosis of SRPL was based on the morphological, immunohistochemical, immunophenotypic, and molecular examinations of the splenic biopsy specimens, blood and bone marrow (BM) tests in 4 (4.6%) cases. Results. There was significant splenomegaly in all SRPL cases, lymphocytosis in 56 to 94% (leukocytes, 55 and 75·109/l in 2 cases), circulation of hairy lymphocytes with the phenotypes CD20+ (markedly), CD11c+/±, CD103+/± (weakly), LAIR-1+, CD25–, CD5–, CD10–, and CD23–, which did not contain tartate-resistant acid phosphatase, without BRAFV600E mutation, BM with insignificant lymphoid infiltration of CD20+, CD25–, Annexin 1–, and Cyclin D1–. The weight of the spleen averaged 3900 g (1450-9500 g); its tissue exhibited lymphoid infiltration of the red pulp with the phenotypes CD20+, DBA.44+, CD25–, Annexin1–, Cyclin D1–, CD103–, CD123–, CD27–, focal СD11c±, and TRAP±. Four patients (2 after splenectomy (SE) and 2 after SE and chemotherapy with cladribine and rituximab) are being followed up in remission. Conclusion. SRPL is a rare disease that should be presumed to be in significant splenomegaly and lymphocytosis with hairy lymphocytes, which have only some markers for classical hairy cell leukemia (HCL), in minor BM lesion. SE is the standard for diagnosis and treatment. The differential diagnosis of SRPL with HCL has clear criteria and that with HCL-v is undetected.

Splenic marginal zone B-cell lymphoma (SMZBCL) is a rare non-Hodgkin B-cell lymphoma that presents with morphologically mature lymphoid cells corresponding in their immunological characteristics to secondary follicular marginal zone lymphocytes. It is clinically characterized by splenomegaly, moderate lymphocytosis, usually focal bone marrow lesion, sometimes moderate of monoclonal immunoglobulin in the serum (generally IgM or IgG) and/or urea, and a relatively benign course. Leishmaniasis is a transmissible natural focal infectious endemic disease that has a great diversity of clinical manifestations. The authors describe Russia’s first case of SMZBCL concurrent with visceral leishmaniasis in a 52-year-old female patient admitted to a hematology hospital with weakness, splenomegaly, and lymphadenopathy. The simultaneous detection of lymphoma and leishmaniasis in the same biopsy specimen is extremely rare. Visceral leishmaniasis should be borne in mind as an opportunistic infection in patients with malignancies, particularly in immunocompromised persons who live or have stayed in the endemic areas.

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.

AIM: To give the results of an investigation conducted at the Hematology Research Center (HRC), Ministry of Health of the Russian Federation (MHRF), to treat adult patients with acute promyelocytic leukemia (APL) according to the AIDA protocol elaborated by Spanish investigators/MATERIAL AND METHODS: The investigation enrolled 33 patients diagnosed with APL verified by cytogenetic and molecular studies, who had been treated at the HRC, MHRF, in July 2009 to January 2012. The patients classified in the low-, intermediate-, and high-risk groups were 30, 46.7; and 23.3%, respectively. The analysis was made in January 2013/RESULTS: The number of patients who achieved complete remission, as well as the mortality rates during remission induction were wholly comparable to those previously obtained when using the 7+3+ATRA protocol: 90.3 and 9.7%, respectively. One patient in remission died (3.6% mortality rate). The likelihood of recurrence in this investigation was high (21%), which was due to gross noncompliance with maintenance therapy. On examining the clearance of the malignant clone by FISH and polymerase chain reaction, a naturally chimeric transcript identified by a molecular study was statistically significantly more frequently revealed during postinduction therapy, which was associated with different sensitivity of the techniques. Comparison of changes in the disappearance of a chimeric marker for APL with the AIDA and 7+3+ARTA programs showed that the clearance of the malignant clone was much slower/CONCLUSION: The AIDA program is a highly effective treatment protocol for patients with APL.

The term mastocytosis (MC) encompasses a group of rare diseases characterized by the tumorous proliferation of clonal mast cells and the infiltration of one or several organs. The clinical picture of MC is extremely diverse from skin lesions that can spontaneously regress to the aggressive disease forms associated with organ dysfunction and short survival. Nowadays, the 2008 WHO classification identifies 7 MC subtypes. The disease is diagnosed on the basis of its clinical manifestations and detection of tumorous mast cell infiltrations via morphological, immunohistochemical, immunophenotypic, genetic, and molecular examinations. Abnormal mast cells are characterized by the atypical morphology and pathological expression of CD25 and CD2 antigens. Enhanced serum tryptase activity is a common sign in all MC subtypes. More than 90% of the patients have D816V KIT mutations in the mast cells. This paper reviews the literature. Three cases are described as a clinical example in patients with different MC subtypes.

To interpret hematopoietic cell myelodysplastic changes found during the primary diagnosis of myelodysplastic syndromes or other diseases and during therapy is an enormously complex clinical and laboratory problem. In what cases do these changes serve as a manifestation of clonal disease and in what cases are these changes a result of various effects? Alimentary, toxic factors, infectious agents, and iatrogenic effects may cause myelodysplastic signs in the hematopoietic cells. This review depicts diverse hematopoietic cell dysplastic changes that can be observed as a result of the effects of one drug or another, toxic factors, and infectious agents.

To estimate a change in myelodysplasia in decitabine-treated patients with myelodysplastic syndromes (MDS).Thirteen MDS patients from a high-risk group were examined; 75 bone marrow puncture specimens and 67 bone marrow trepanobiopsy specimens from these patients were analyzed before and after decitabine treatment. Dysplastic changes in the hematopoietic cells were monitored during the treatment.The dysplastic changes in the hematopoietic cells are a morphological portrayal of the ineffective hematopoiesis in patients with MDS. The study has indicated that the use of the hypomethylating agent decitabine promotes the restoration of cell differentiation to mature forms, causing hematopoiesis to be more effective. The incidence of myelodysplasias (including mixed double- and triple-lineage ones) was statistically significantly reduced by decitabine treatment, which was associated with a positive response to treatment as a whole. The count of cells with dysplastic features remained unchanged in patients with therapy resistance or further disease progression.Analysis of myelodysplastic manifestations in different hematopoietic lineages in patients with MDS should be based on the comprehensive dynamic assessment of cytological and histological parameters at both the primary diagnosis of the disease and different stages of treatment. With a response to decitabine therapy (as shown by the results of aspiration and trepanobiopsy), all cell lines displayed reduced myelodysplastic changes, indirectly indicating a decrease of the abnormal clone itself in high-risk MDS patients.

To generalize hematologists' experience of the diagnosis and differential diagnosis of splenic red pulp lymphoma (SRPL).Eighty-seven splenic biopsy specimens taken from patients with different B-cell lymphoproliferative diseases were examined in the Hematology Research Center in 2013-2014. The diagnosis of SRPL was based on the morphological, immunohistochemical, immunophenotypic, and molecular examinations of the splenic biopsy specimens, blood and bone marrow (BM) tests in 4 (4.6%) cases.There was significant splenomegaly in all SRPL cases, lymphocytosis in 56 to 94% (leukocytes, 55 and 75·109/l in 2 cases), circulation of hairy lymphocytes with the phenotypes CD20+ (markedly), CD11c+/±, CD103+/± (weakly), LAIR-1+, CD25-, CD5-, CD10-, and CD23-, which did not contain tartate-resistant acid phosphatase, without BRAFV600E mutation, BM with insignificant lymphoid infiltration of CD20+, CD25-, Annexin 1-, and Cyclin D1-. The weight of the spleen averaged 3900 g (1450-9500 g); its tissue exhibited lymphoid infiltration of the red pulp with the phenotypes CD20+, DBA.44+, CD25-, Annexin1-, Cyclin D1-, CD103-, CD123-, CD27-, focal СD11c±, and TRAP±. Four patients (2 after splenectomy (SE) and 2 after SE and chemotherapy with cladribine and rituximab) are being followed up in remission.SRPL is a rare disease that should be presumed to be in significant splenomegaly and lymphocytosis with hairy lymphocytes, which have only some markers for classical hairy cell leukemia (HCL), in minor BM lesion. SE is the standard for diagnosis and treatment. The differential diagnosis of SRPL with HCL has clear criteria and that with HCL-v is undetected.Цель исследования. Обобщить опыт гематологов по диагностике и дифференциальной диагностике лимфомы красной пульпы селезенки (ЛКПС). Материалы и методы. За 2013-2014 гг. в ФГБУ ГНЦ выполнено исследование биоптатов 87 селезенок, удаленных при различных В-клеточных лимфопролиферативных заболеваниях. В 4 (4,6%) случаях на основании морфологического, иммуногистохимического, иммунофенотипического, молекулярного исследований биоптата селезенки, проб крови, костного мозга (КМ) установлен диагноз ЛКПС. Результаты. Во всех случаях ЛКПС наблюдалась значительная спленомегалия, лимфоцитоз от 56 до 94% (в 2 случаях с лейкоцитозом 55·109 и 75·109/л), циркуляция 'ворсинчатых' лимфоцитов с фенотипом CD20+(ярко), CD11c+/±, CD103(слабо)+/±, LAIR-1+, CD25–, CD5–, CD10–, CD23–, не содержащих тартратустойчивую кислую фосфатазу, без мутации BRAFV600E. КМ с незначительной лимфоидной инфильтрацией CD20+, CD25–, Annexin 1–, Cyclin D1–. Масса селезенки составила в среднем 3900 г (1450-9500 г), в ткани выявлена лимфоидная инфильтрация красной пульпы с фенотипом CD20+, DBA.44+, CD25–, Annexin1–, Cyclin D1–, CD103–, CD123–, CD27–, очагово СD11c± и TRAP±. Пациенты наблюдаются в ремиссии заболевания: 2 больных после спленэктомии (СЭ), 2 после СЭ и химиотерапии кладрибином и ритуксимабом. Заключение. ЛКПС - редкая патология, предполагать которую следует при значительной спленомегалии и лимфоцитозе с ворсинчатыми формами лимфоцитов, имеющими лишь часть маркеров классического ВКЛ, при скудном поражении КМ. Стандартом диагностики и лечения является СЭ. Дифференциальный диагноз с ЛКМЗ и ВКЛ имеет четкие критерии, с в-ВКЛ - не определен.

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

To evaluate the efficacy of cyclosporin A (CsA) in patients with myelodysplastic syndromes (MDS) and to identify determinants of a response to this therapy.The efficacy of CsA was evaluated in 52 patients (30 men and 22 women aged 16 to 74 years) with MDS. Thirty-two patients were given CsA as first-line therapy; 20 patients took the agent after prior therapy. CsA was used in a daily oral dose of 5 mg/kg. Its efficacy was evaluated following 3, 6, and 12 months. Actuarial survival was determined by the Kaplan-Meier method.The efficacy of CsA used as first- and second-line therapy was 56 and 55%, respectively; complete remissions were achieved in 19 and 20% of cases. Baseline refractory anemia (RA) transformed to RA with excess blasts (RAEB) in 31% of cases; baseline RAEB did to acute myeloid leukemia in 34%. Overall survival was significantly associated with bone marrow (BM) blast cell percentage (5% or5%; p = 0.0009), BM cellularity (hypoplasia and focal hypoplasia of hematopoiesis or BM hyperplasia; p = 0.03), focal polyclonal lymphoid infiltration in the BM (p = 0.01) and karyotype anomalies (low, moderate, and high risks; p = 0.001).CsA is the drug of choice in treating patients with MDS, including RA, RA with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, with hypoplasia of hematopoiesis, with nodular polyclonal lymphoid infiltration in the BM, a normal karyotype or changes corresponding to a low or moderate IPSS risk.

Introduction The majority of clinical recommendations on MDS indicate the use of IST for low-risk hypoplastic MDS patients. ATG followed by cyclosporine A (CSA) is recommended for younger pts with normal karyotype or with +8, CSA - for older patients with autoimmune phenomenon or hypoplastic bone marrow. There are no reports on the use of CSA with splenectomy as a combined IST for MDS patients. Here we report the long term (20 years) results of the single center trial comprising 61 MDS pts treated with CSA as the first or the second line treatment + splenectomy. Patients and methods. Since 1995 till June 2015, 61 patients were included in the combined IST protocol. There were 34 males, 27 females; median age constituted 39 years (16-74), refractory cytopenias with multileaneage dysplasia = 46, RAEB1/2 = 15; IPSS - low-risk= 4, intermediate 1 =40, intermediate-2 =9, high =4; no risk evaluation - 4 patients. All patients had trepanobiopsy evaluation, half of them - bilateral. It worth to note that bilateral trepanobiopsy permitted to redefine cellularity in 15% of patients. Pure hypoplastic forms of MDS were registered in 38 patients (63%), combination of hypoplasia with hyperplasia or normal cellularity - in 10 (16%), hyperplastic forms - in 13 (21%); non-clonal lymphoid nodules in b/m were detected in 29 pts (46%); fibrosis - in 7. Cytogenetics was done in 57 pts, 32 had normal karyotype; 5 had trisomy 8; 8 - high risk cytogenetics (-7/7q-, complex); 8 - different intermediate. Cyclosporine A was applied at a dose 5 mg/kg per day, followed by reevaluation of response at 2-3 months. In case of response CSA was continued, if there was no response or it was inadequate - splenectomy was done followed again by CSA; if progression occurred - CSA was stopped. We consider splenectomy as a component of the programmed IST as it leads to removement of a big lymphoid organ. For younger patients ATG for 20 mg/kg for 5 days could become the 2nd or the 3rd line of treatment. For patients with sibling donors allogeneic HSCT was an option. Analysis was carried out in June 2015. The patients were grouped for analysis according to cellularity (hypo vs hyper, in case of combination hypo with hyper/normal the case was considered as hypocellular), % of b/m blast cells (<> 5%), IPSS index (low/int-1 vs int-2/high), cytogenetics, the presence of lymphoid nodules. Results. CSA was started as the 1st line treatment in 42 patients, as the second line (after ATG or splenectomy or ESA) - in 20. 5 patients were transplanted from sibling donors. 35 patients received CSA as monotherapy (16 of them had a progression or a transformation to AML). Totally splenectomy was performed in 20 patients, in 8 patients it was followed by additional immunosuppression with ATG (9 patients) or MMF (1 patient). Splenectomy was performed by laparoscopy, no deaths or sever complications were noted. Half of the splenectomized patients achieved sustained response after operation and continuation of CSA. On the whole 18 patients had progression to RAEB or transformation to AML (1 from low-risk group, 7 - int1, 6 - int2, 5 - from high risk). Complete remission was achieved in 15 patients (24%), with overall response rate of 56% (n=34) with a median duration of response - 21 months (1-230 mo). The 20-years survival data revealed highly statistical difference between hypoplastic forms of MDS vs hyperplastic (38% vs 0%), bone marrow blast cells less vs more than 5% (43% vs 5%), IPSS categories low/int1 vs int2/high (50% vs 0%), cytogenetics favorable vs intermediate vs high (62% vs 35% vs 0%) (Pic.1). No differences were detected in patients with or without lymphoid nodules in b/m (38% vs 35%). Conclusions Our small but prolonged study has demonstrated a substantial long-term efficacy of the combined IST. CSA followed by splenectomy is a reasonable treatment approach in MDS patients with hypoplastic features in bone marrow, normal or intermediate karyotype, low blast cell count, low/int1 IPSS score. Pic.1 Overall survival of MDS patients treated with combined IST depending on cellularity, blast cells count, cytogenetic features and IPSS score. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.