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Aim: to analyze the first neurological manifestation in patient with thrombotic thrombocytopenic purpura (TTP). Material and methods. The appeals from physicians who suspected TTP were included in the study. The neurological symptoms in 40 patients with TTP were also analyzed. Results. Among 208 physician appeals about the suspicion of TTP and the referral of plasma samples for testing of ADAMTS13 activity, there were 2% of neurologists. The diagnosis of TTP was confirmed in 40 patients. 9 (22.5%) had no neurological symptoms, and 31 (77.5%) had neurological disorders. Patients with neurological symptoms were older than patients without neurological symptoms (median 37 years and 31 years, p = 0.006). Neurological symptoms were less frequently observed in pregnancy-associated TTP (p = 0.008). Among neurological symptoms there were speech disorders (40%), headache (30%), cognitive deficits (32.5%), depression of consciousness (22.5%), paresis (25%), sensation disorders (20.5%), seizures (10%). Magnetic resonance imaging/computed tomography (MRI/CT) revealed ischemic stroke in 47.5%, hemorrhagic stroke in 15%. In 6 patients, despite neurological symptoms, no pathology was detected with MRI/CT. In 4 patients, in the absence of neurological symptoms, MRI/CT revealed ischemic foci in the brain. 8 patients died: 2 patients died from sepsis, 6 - from ischemic stroke. In surviving patients, neurological symptoms regressed after remission. Conclusion. Neurological symptoms are detected in most patients with TTP. Brain MRI/CT should be performed in all patients with TTP

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 tactics of therapy for elderly comorbid patients with mantle cell lymphoma with unfavorable prognosis factors (complex karyotype, 17p13 deletion, mutations in the TP53 gene) have not been developed. The use of intensive chemotherapy regimens and transplantation of allogeneic hematopoietic stem cells (allo-HSCT) is impossible due to severe comorbidity in elderly patients. A rational approach is the use of a combination of ibrutinib and venetoclax. As an alternative to allo-HSCT, a new option for elderly patients with poor prognostic factors is Chimeric Antigen Receptor T-cell therapy (CAR-T) cell therapy.Aim — to present the experience of using ibrutinib and venetoclax with CAR-T-cell therapy in the first line of treatment in an elderly patient with MCL with a mutation in the TP53 gene and hyperleukocytosis.Main findings. Patient M., 68 years old. The examination revealed hyperleukocytosis 978 × 109/L, anemia (55 g/L), thrombocytopenia (30 × 109/L), and splenomegaly 250 × 180 mm. According to the results of laboratory studies, the diagnosis of lymphoma from mantle cells with a complex karyotype, deletion 17p13, 13q14 and mutation p.R248W in exon 7 of the TP53 gene (VAF = 26 %) was verified. For cytoreductive purposes, two sessions of leukocytapheresis and prephase with cyclophosphamide (200 mg/m2) and dexamethasone (10 mg/m2) were performed. From day 3, therapy with ibrutinib 420 mg/day and venetoclax 100 mg/day was started. After 2 days, the leukocytes were 0.7 × 109/L, and the size of the spleen decreased, as a result of which the development of tumor lysis syndrome was noted. As a result of intensive therapy, the patient’s condition stabilized, which allowed him to resume treatment. After 7 days, the number of leukocytes was 2.5 × 109/L, neutrophils — 70 %, platelets — 90 × 109/L, hemoglobin — 95 g/L. According to immunophenotyping, the population of B-lymphocytes was 4 %. According to NGS data, the allelic load of the mutation in the TP53 gene is 0.8 %. The patient underwent anti-CD19 CAR-T-cell therapy and achieved complete remission. Three months after therapy, MRD remains-negative remission and the persistence of CAR-T cells is determined.

Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity.Aim — to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML.Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study; average age — 32; stage > I — in 60 %; extramediastinal lesions — in 14.7 %; bulky disease — in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed; ctDNA was determined to assess the completeness of remission.Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy; 2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy; 2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission; 7 (44 %) retained pathological activity (D4–5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3–6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission.Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose shortpulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the “PML-19” program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.

Introduction. Life-threatening complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) can have a significant influence on the short-term and long-term prognosis in recipients of hematopoietic stem cells (allo-HSCs).Aim — to determine the life-threatening complications and the risk factors of their occurrence and to evaluate the short-term and long-term prognosis in critically ill allo-HSCs recipients.Materials and methods. All patients over the age of 18 who underwent allo-HSCT from 01.01.2012 to 01.01.2022 were included in the retrospective study. Patients were divided into two groups: those who required intensive care unit (ICU) admission and those who did not require ICU admission. In the group of ICU admitted allo-HSCs recipients the reasons of ICU admission, timing of their occurrence and the results of life support were recorded. The risk factors of life-threatening complications occurrence and prognostic factors were analyzed.Results. In total, 174 (26.7 %) of 652 allo-HSCs recipients required ICU admission. The risk factors of life-threatening complications were: allo-HSCT in patients with acute leukemia who did not achieve complete remission (hazard ratio (HR) = 2.10; 95 % confidence interval (95% CI): 1.28–3.44; p = 0.003), allo-HSCT without conditioning in patients with hematopoietic aplasia after chemotherapy (HR = 30.63; 95% CI: 8.787–107.04; p < 0.001), graft failure (HR = 2.51; 95% CI: 1.58–3.97; p < 0.001) and poor graft function (HR = 2.85; 95% CI: 1.6–5.05; p < 0.001), acute graft versus host disease (GVHD) (HR = 2.04; 95% CI: 1.459–2.85; p < 0.001). The main reasons of ICU admission were sepsis and/or septic shock (SS) (27.9 %), acute respiratory failure (23.9 %), neurological disorders (17.7 %). The type and periods of allo-HSCT influenced the timing and structure of critical illnesses. The ICU mortality rate after all ICU admissions and readmissions was 59.8 % with a maximum follow-up of 9 years. The risk factors of ICU mortality were the occurrence of critical conditions after +30 days of allo-HSCT, the need for mechanical ventilation and vasopressors. The overall survival (OS) rate of ICU admitted allo-HSCs recipients was 13.8 %. Sepsis and/or SS that occurred in the early phase after allo-HSCT were characterized by the most favorable long-term outcome (OS — 43.8 %) among all complications of the peritransplantation period. The OS of patients discharged from the ICU was worse than OS of patients who did not require ICU admission (34.6 % vs. 58.3 %; p = 0.0013). Conclusion. Transplant centers should have a specialized ICU because more than a quarter of allo-HSCT recipients experience life-threatening complications at different allo-HSCT periods. Sepsis and SS occurring in the early pre-engraftment phase had a more favorable prognosis than other life-threatening complications. The long-term outcomes in allo-HSCs recipients who survived critical illness are worse than in recipients who did not require ICU admission.

Introduction. Acquired hemophilia is a rare autoimmune disease caused by an inhibitor to clotting factor VIII (FVIII). It complicates the course of many diseases, in particular autoimmune diseases, and in women is often associated with pregnancy.Aim — to present a case of successful treatment of a patient with acquired hemophilia using long-term continuous infusion of rFVIIa and inhibitor eradication as a result of immunosuppressive therapy.Main findings. A clinical observation of severe hemorrhagic syndrome in a patient with acquired hemophilia associated with pregnancy is presented. Uterine bleeding in the patient after spontaneous delivery, refractory to standard hemorrhagic syndrome treatment, required multiple surgical interventions. Laboratory tests showed prolongation of APTT, CT in the INTEM rotational thromboelastometry test, a decrease in plasma FVIII activity and presence of inhibitor to FVIII. Vacuum-assisted closure was applied to treat infected laparotomy wound. Therapy for acquired hemophilia consisted of hemostatic therapy and the inhibitor eradication. Hemostatic therapy included a continuous infusion of rFVIIa at a rate of 30 μg/kg/h with a gradual decrease up to 9.6 μg/kg/h, as well as its fractional administration before every surgery at a dosage of 80 μg/kg. The effectiveness of the therapy was assessed by the dynamics of CT in the INTEM test and the shortening of the APTT. The inhibitor eradication was achieved by prednisolone therapy, combined immunosuppression with rituximab and azathioprine, followed by its replacement with cyclophosphamide. As a result, the hemorrhage was stopped, reference plasma activity of FVIII and eradication of the inhibitor were reached.

Introduction. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often complicated by life-threatening conditions.Aim — an analysis of the life-threatening complications in recipients of allogeneic hematopoietic stem cells (allo-HSCs)Main findings. From 10 to 50 % of allo-HSC recipients need to be admitted to the intensive care unit (ICU) due to the development of life-threatening complications. The reasons for ICU admission are acute respiratory failure, sepsis, graft-versus-host disease, veno-occlusive disease, thrombotic microangiopathy, cytokine release syndrome, engraftment syndrome, etc. Conditioning regimen, donor type, stem cell source, underlying disease state and patient comorbidity are the risk factors associated with development of life-threatening conditions. The main prognostic factors of unfavorable ICU outcomes in allo-HSC recipients are the severity of multiple organ dysfunction and the need for organ support.

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.

Introduction. The introduction of chimeric antigen receptor (CAR) T-cell therapy is a promising treatment of patients with relapsed or refractory (R/R) B-cell lymphoproliferative diseases (LPDs).Aim — to present the results of CAR-T-cell therapy of 6 adult patients with B-cell LPDs.Materials and methods. This is a pilot study conducted in adult patients with R/R or persistent minimal residual disease B-cell LPDs treated with CAR-T-cells. The study was approved by a local ethical committee of National Research Center for Hematology. Patients did not have alternative options for effective and safe treatment. All patients signed an informed consent. All patients were lymphodeplated with fl udarabine and cyclophosphamide for 4 days before the introduction of CAR-T-lymphocytes. Cytokine release syndrome (CRS) was prevented by tocilizumab on the day of CAR-T-cell administration. The effi cacy and safety of CAR-T-cell therapy was evaluated.Results. From 01.01.2020 to 01.01.2022, 10 CAR-T-cell infusions were performed for 6 adult patients (age 19–68 years, median — 32 years) with B-cell LPDs: 4 — R/R B-acute lymphoblastic leukemia, 1 — R/R diffuse large B-cell lymphoma, 1 — persistence of MRD in mantle cell lymphoma. In all patients with a R/R, median — 4 (2–5) lines of chemotherapy and/ or immunotherapy were performed before CAR-T-cell therapy. CD19 CAR-T-cells received 3 patients, CD19/CD22 CAR-Tcells — 2 patients, CD19 and CD20 CAR-T-cells received 1 patient. Autologous CAR-T-cells received 4 (66 %) patients, allogeneic CAR-T-cells received 1 patient, and one patient had two CAR-T-cell administrations — 1 autologous and 1 allogeneic. The median number of CAR-T-cells was 0.5 × 106 /kg (from 0.1 × 106 /kg to 3 × 106 /kg). In 7 (87.5 %) of the 8 cases after CAR-T-cell administration, overall response to therapy (complete or partial remission) was achieved, and complete remission was achieved in 6 (75 %) cases. Side effects were noted after 8 of 10 CAR-T-cell transfusions: CRS in 40 % (CRS 1 — 10 %, CRS 2 — 20 %, CRS 3 — 10 %), ICANS in 10 %, tumor lysis syndrome in 20 %, multi-organ dysfunction syndrome in 10 %. There were no lethal complications due to CAR-T-cell administrations. The median follow-up period was 6 (1–16) months. Of the 6 patients, 2 (33 %) died from relapses and progression of LPD. One (17 %) patient died in complete remission from infectious complications. Three (50 %) patients are observed till now. The median time of CAR-T-cell circulation was 33 (6– 60) days.Conclusion. CAR-T-cell therapy is a promising treatment for R/R B-cell LPDs and LPDs with persistence of MRD after cytoreductive therapy. This type of therapy requires a multidisciplinary approach.

Introduction. The SARS-CoV-2 infection (COronaVIrus Disease 2019, COVID-19) usually progresses uncomplicated in an acute respiratory form but causes frequent severe illness in oncohaematological patients.Aim — analysis of the management and efficacy of medical aid at a haematology clinic during the COVID-19 pandemic.Patients. The clinic admitted 2,130 patients in April 20 — November 20, 2020, with 920 of them triaged into observatory wards. At the time of admission, 907 (98.5 %) patients were SARS-CoV-2 RNA-negative, with 13 hospitalised without nasopharyngeal swab tests. Patient nosology: 235 (25.5 %) lymphoma, 152 (16.5 %) multiple myeloma, 131 (14.2 %) acute leucaemia, 86 (9.3 %) haemophilia, 35 (4 %) Gaucher’s disease, 17 (1.8 %) Waldenstrom macroglobulinemia, 16 (1.7 %) aplastic anaemia, 153 (16.6 %) various surgical diseases, 81 (8.8 %) other haematological diseases and 14 (1.6 %) were bone marrow donors.Results. Among the 920 patients admitted to the observatory, 139 (15 %) were severe and 653 (71 %) had a moderate condition. Fever was reported in 124 (13.5 %) patients at admission. Chest computed tomography (CT) was performed in 809 patients, with recent lung inflammation detected in 121 (15 %) cases. Twenty four (2.6 %) patients were revealed SARS-CoV-2-positive, with 20 diagnoses PCR-verified and four — in chest CT. Ten patients were diagnosed positive in routine examination or at a specialty unit as fever aggravated. Thus, a two-staged SARS-CoV-2 screening with PCR and chest CT allowed an extra 2.6 % detection of COVID-19 cases despite negative tests at admission.Conclusion. The observatory management has reduced the likelihood of nosocomial COVID-19 and ensured a continued supply of specialty medical aid.

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

Introduction. Mutations in the TP53 gene in patients with mantle cell lymphoma (MCL TP53+) are associated with a low response to intensive chemotherapy (CT) and adverse outcomes. Allogeneic haematopoietic stem cells transplantation (allo-HSCT) is a curative approach in MCL-TP53+ patients.Aim. Efficacy and safety assessment of allo-HSCT in MCL-TP53+ patients.Main findings. During 2016–2020, allo-HSCT in MCL TP53+ was performed in three patients. Two of them were grafted from HLA-identical unrelated donors, and one — from a haploidentical donor. Pre-transplant conditioning was “fludarabine + treosulfan + melphalan” in one case, and “fludarabine + busulfan” — in the other two. In three patients, leukocyte and platelet counts were recovered at days +18 and +20, +17 and +21, +19 and +16 after allo-HSCT, respectively. Acute graft-versushost disease (aGVHD) was observed in all patients (grade I — in 2 patients, grade IV — in 1 patient). One patient developed chronic GVHD (cGVHD) of moderate grade. All three patients exhibited complete remission and 100% donor chimerism in allo-HSCT follow-up of 6, 15 and 40 months, respectively.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease, disease, characterised by microangiopathic hemolytic anaemia, consumption thrombocytopenia, and organ dysfunction. The pathogenesis of TTP is attributed to the deficiency in the activity of the metalloproteinase ADAMTS13, specific von Willebrand factor cleaving protease. TTP is suspected when detecting microangiopathic hemolytic anemia, thrombocytopenia, damage to various organs. Diagnosis of TTP is confirmed by the detection of ADAMTS13 activity in plasma less than 10%. Plasma samples for the study of ADAMTS13 activity should be taken before the start of plasma transfusions or plasma exchange. In patients with severe ADAMTS-13 deficiency autoantibodies anti-ADAMTS13 and inhibitor ADAMTS13 should be investigated. Anti-ADAMTS13 antibodies belonging to IgG not always have inhibitory effects. The inhibitory effect of anti-ADAMTS13 antibodies is confirmed by mixing test. All patients with the first established diagnosis of TTP should be examined for mutations of the ADAMTS13 gene.

Hemostatic disorders play an important role in the pathogenesis and clinical manifestations of COVID-19. The purpose of the research was a detailed consideration of the pathogenesis, clinical manifestations, and methods of diagnosing and treatment of coronavirus-induced coagulopathy (CIC). At the onset of COVID-19, hypercoagulability is detected, and consumption coagulopathy and disseminated intravascular coagulation (DIC) syndrome are usually observed at later stages of the disease. In the pathogenesis of hypercoagulation in patients with COVID-19, proinflammatory cytokines, hyperfibrinogenemia, increased blood levels of von Willebrand factor, factor VIII, neutrophilic extracellular traps, platelet activation, production of antiphospholipid antibodies, microvesicles are of importance. Laboratory findings show increased plasma concentrations of D-dimer, fibrinogen, a longer prothrombin time and a decrease in the number of platelets. The cumulative incidence of thrombotic complications ranges from 21 to 31%. Thrombosis risk factors are intensive care unit stay, leukocytosis, and a high plasma D-dimer concentration. Differential diagnosing of CIC should be carried out with disseminated intravascular coagulation, sepsis-induced coagulopathy, antiphospholipid, hemophagocytic syndromes, thrombotic microangiopathy, and heparin-induced thromocytopenia. CIC may be complicated by sepsis, antiphospholipid syndrome, hemophagocytic syndrome, thrombotic microangiopathy, and heparin-induced thrombocytopenia.The main therapy is low molecular weight heparins treatment. Treatment recommendations are provided.

Remission induction can be associate, with the life threatening complications and transfer to ICU of de novo acute myeloid leukemia (AML) patients (pts). We evaluate influence of transfer to ICU and life threatening complication on early mortality and long - tram survival of de novo AML pts.Retrospective study. All de novo AML pts younger than 60 years old admitted in the National Research Center for Hematology from 2013 to 2016 years were enrolled in the study. Patients were divided into 2 groups: pts who were required ICU admission during remission induction (ICU-pts) and pts who did not require ICU admission and received chemotherapy only in hematology ward (non-ICU pts). The reasons for ICU admissions and results of life support were analyzed. Overall survival (OS) were assessed by the Kaplan-Meier method, long rank value p.Цель. Индукция ремиссии у больных острыми миелоидными лейкозами (ОМЛ) может привести к угрожающим жизни осложнениям, требующим перевода в отделение реанимации и интенсивной терапии (ОРИТ). Цель работы - оценить влияние интенсивной терапии угрожающих жизни осложнений на краткосрочные и отдаленные результаты лечения больных ОМЛ. Материалы и методы. В ретроспективное исследование включены больные с de novo ОМЛ старше 18 лет, которые были разделены на группы, кому потребовался перевод в ОРИТ (группа с ОРИТ) и не нуждавшихся в переводе в ОРИТ (группа без ОРИТ). Регистрировали структуру и результаты лечения критических синдромов, сравнивали между группами демографические показатели, молекулярно - цитогенетический риск, проводившуюся химиотерапию, краткосрочные и отдаленные результаты лечения ОМЛ. Использовали методы описательной статистики, вероятность дожития по методу Каплана-Майера. Результаты. В исследование включено 76 больных ОМЛ. Перевод в ОРИТ потребовался 37% больных. Причины перевода: острая дыхательная недостаточность (50%), септический шок (14,3%), нарушение мозгового кровообращения (17,9%), экстренное родоразрешение (10,7%), острая аритмия (7,1%). Пациенты группы с ОРИТ не отличались от пациентов группы без ОРИТ по возрасту, частоте цитогенетически неблагоприятных форм ОМЛ, но в группе с ОРИТ были более выраженные анемия, лейкоцитоз, большее количество бластных клеток в крови и костном мозге. Факторами неблагоприятного исхода в ОРИТ были септический шок и искусственная вентиляция легких. В группе ОРИТ 28-дневная общая выживаемость (ОВ) составила 64,3%, 5-летняя ОВ - 43,2%, 5-летняя безрецидивная выживаемость (БРВ) - 34%, медиана БРВ - 16,4 мес; в группе без ОРИТ - соответственно 100, 53, 44% и 23,5 мес (p=0,504). Заключение. Отдаленные результаты лечения больных ОМЛ, которым понадобилась интенсивная терапия, значимо не отличаются от результатов лечения больных без этих осложнений.

The article provides a literature review on the use of the L-asparaginase (ASP) in acute lymphoblastic leukemia (ALL) and describes two clinical cases. During the treatment with ASP as part of remission induction therapy thrombotic and hemorrhagic complications in the central nervous system were registered. In both cases these complications were associated with reduced plasma levels of antithrombin III (АТ), hypofibrinogenemia and thrombocytopenia. The risk factors for thrombohemorrhagic complications in ALL patients during ASP treatment are reviewed including combined ASP + anthracycline therapy, oral contraceptives, glucocorticosteroids, thrombophilia and the presence of central venous catheter (CVC). Possible mechanisms of thrombosis as well as the timing of its occurrence and possible localisation are discussed. The article considers different strategies for prevention and treatment of thrombotic and hemorrhagic complications in ALL patients receiving ASP. In all ALL patients receiving ASP plasma levels of fibrinogen and AT should be assessed before treatment initiation, on day 3 after the injection and further every 5 to 7 days within a period of 3 weeks after the injection. Novel oral anticoagulants are not dependent on blood AT levels and may be used for prevention and treatment of thrombotic and hemorrhagic complications associated with ASP intake. Finally, recommendations for the correction of AT levels and hypofibrinogenemia are given.

The case report of botulinum toxin treatment of gastroparesis in a patient following allogenic bone marrow transplantation is described. The causes of gastroparesis and methods of prevention and treatment are discussed. It was noted that pyloric injection of botulinum toxin can improve symptoms and gastric emptying.

A wide range of toxic complications of BCR-ABL tyrosine kinase inhibitors therapy due to non-targeted inhibition of other protein kinases. This is of particular importance in the treatment of patients with Ph-positive lymphoblastic leukemia, who receive, in addition to tyrosine kinase inhibitors, cytotoxic drugs, enhancing myelotoxicity and, as a consequence, infections and thrombo-hemorrhagic complications. In addition, complex inter-drug interactions lead to the manifestations of combined toxicity. This article presents a case report of patient with relapsed acute Ph-positive lymphoblastic leukemia, treatment of which was accompanied by numerous complications, especially during treatment of II and III generation tyrosine kinases inhibitors.

Primary central nervous system (CNS) lymphomas account for 13-20% of the posttransplant lymphoproliferative disorders (PTLD) and rank among the most aggressive conditions. Reduction of immunosuppressive therapy should be mandatory to treat PTLD, but this is rarely used as the only therapy option. Chemotherapy regimens for PTLD involving the CNS most commonly include high-dose rituximab and high-dose methotrexate and/or cytarabine. The efficiency only of discontinuation of immunosuppressive therapy for PTLD does not exceed 5-10%, but there are no literature data on its efficiency for PTLD involving the CNS. The paper describes a clinical case of achieving long-term remission in a female patient with Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma involving the central nervous system, associated with immunosuppression after kidney transplantation from a related donor, in the absence of chemotherapy during immunosuppressive therapy discontinuation and transplantectomy.Первичные лимфомы с вовлечением центральной нервной системы (ЦНС) составляют 13-20% от посттрансплантационных лимфопролиферативных заболеваний (ПТЛПЗ) и являются одними из наиболее агрессивно протекающих среди них. Редукция иммуносупрессивной терапии должна быть обязательным этапом лечения ПТЛПЗ, но редко применяется как единственный метод терапии. В схемы химиотерапевтического лечения ПТЛПЗ ЦНС включают чаще всего ритуксимаб и метотрексат в высоких дозах и/или цитарабин. Эффективность только отмены иммуносупрессивной терапии при ПТЛПЗ не превышает 5-10%, а об эффективности ее при ПТЛПЗ с вовлечением ЦНС данных в литературе нет. Представлен клинический случай достижения длительной ремиссии у больной с положительной по вирусу Эпштейна-Барр (ЭБВ+) диффузной В-крупноклеточной лимфомой с вовлечением ЦНС, ассоциированным с иммуносупрессией после трансплантации почки от родственного донора, в отсутствие химиотерапевтического воздействия в условиях отмены иммуносупрессивной терапии и трансплантатэктомии.

The described case of FIP1L1-PDGFRА-positive myeloproliferative disease is characterized by an atypical aggressive course to develop severe specific complications as injuries to the brain, heart, lung, and intestine. Pathogenetic therapy with imatinib could stabilize a patient’s state, but failed to produce a complete hematological response. Switching from imatinib to dasatinib could produce sustained clinical, hematological, and molecular remissions.

Gaucher disease is the most common form of hereditary enzymopathies combined into a group of lysosomal storage diseases. The basis for the disease is a hereditary deficiency of the activity of acid β-glucosidase, a lysosomal enzyme involved in the catabolism of lipids, which results in the accumulation of nonutilized cellular metabolism products in the macrophage lysosomes. The main clinical manifestations of type 1 Gaucher disease are cytopenia, hepatomegaly, and splenomegaly, and bone lesion. One of the atypical clinical manifestations of Gaucher disease is damage to the lungs with the development of pulmonary hypertension, which is usually considered within the underlying disease - the development of pneumosclerosis due to macrophage dysfunction. The paper describes a case of progressive pulmonary hypertension in a patient with type 1 Gaucher disease.Болезнь Гоше - наиболее частая форма наследственных ферментопатий, объединенных в группу лизосомных болезней накопления. В основе заболевания лежит наследственный дефицит активности кислой β-глюкозидазы - лизосомного фермента, участвующего в катаболизме липидов, что приводит к накоплению неутилизированных продуктов клеточного метаболизма в лизосомах макрофагов. Основные клинические проявления болезни Гоше I типа: цитопения, гепато- и спленомегалия, поражение костей. Одним из нетипичных клинических проявлений болезни Гоше служит поражение легких с развитием легочной гипертензии, обычно рассматриваемое в рамках основного заболевания - развития пневмосклероза вследствие нарушения функции макрофагов. Приведено описание случая прогрессирующей легочной гипертензии у пациента с болезнью Гоше I типа.

Aim. To evaluate the efficiency of the treatment policy for patients with acute myeloid leukemia (AML) and hyperleukocytosis (HL), which is aimed at preventing rapid hypercytolysis and massive tumor lysis (cytolysis) syndrome and/or at reducing the degree of the latter at the start of induction polychemotherapy. Subjects and methods. In 2010 to 2014, the Hematology Research Center, Ministry of Health of Russia, treated 92 patients with AML, out of them 18 patients were found to have white blood cell counts of 100 to 408∙109/l (median, 130∙109/l) at the onset of the disease. All the examinees received cytoreductive therapy with hydroxyurea and, in presence of leukostasis and/or leukocytosis (≥150∙109/l), with leukocytapheresis. In case of reduced leukocytosis, plasmapheresis was carried out to prevent (treat) cytolysis. Daunorubicin was injected on days 3—5 of the 7+3 induction cycle. Results. The signs of leukostases were detected in more than half of the 18 patients with higher white blood cell counts: 13 (72%) with lung injury, including 5 of them with signs of respiratory distress syndrome, 6 (27.8%) with neurological symptomatology, 7 (38.9%) with disseminated intravascular coagulation syndrome, including 1 with intracranial hemorrhage. Cytoreduction therapy with hydroxyurea (10 mg/kg/day) was performed 1—5 (median 2) days before initiating induction chemotherapy in 17 patients; 9 patients underwent 1—2 (median 2) leukocytapheresis sessions. Sixteen patients received 1—4 (median 2) plasmapheresis sessions prior to and within the first days of the 7+3 treatment regimen. Daunorubicin (60 mg/m2) was administered to 16 patients on days 5—7 of the 7+3 cycle and to 2 patients on days 3—5 of the cycle. There were no signs of severe cytolysis with the development of multiple organ dysfunction in any patient. 50% (9/18) achieved remission after the first 7+3 cycle and 7 more examinees did after the second cycle. Thus, the remission rate was 89%; early mortality was 5.5% (1/18), three-year overall and relapse-free survival rates were 50%. Conclusion. Adequate cytoreductive and accompanying therapies for AML with HL can virtually completely prevent massive tumor cytolysis syndrome and early mortality during the first days of induction chemotherapy.

Aim. To ascertain indications to standard (CHOP-21/R-CHOP-21) and intensive (mNHL-BFM-90) treatment in patients with diffuse large B-cell lymphosarcoma (DLBCL) with involvement of lymphoid organs. Material and methods. The trial, performed from January 2002 to December 2010, enrolled 139 DLBCL patients with affected lymph nodes (LN), tonsils, spleen, bone marrow (BM). The diagnosis was made according to WHO criteria. The patients were examined according to the protocol of lymphoproliferative diseases. Biopsy material from all 139 patients was studied immunohistochemically on paraffin blocks (LN, tonsils, spleen, BM) using a wide panel of antibodies. The same examinations of BM were made in all 18 cases of BM involvement. Cytogenetic examination was performed in 106 patients: 48 standard cytogenetic tests, 139 - FISH for t (14;18) as well as rearrangement of locus 3q27. Patients with a poor prognosis (n = 86, 61.8%) received intensive therapy according to mNHL-BFM-90 program. The signs of a poor prognosis were the following: massive tumor (tumor size more than 7.5 cm), invasion into the adjacent organs or tissues, stage III-IV disease by Enn-Erbor, high concentration of LDG. Patients without a poor prognosis (n = 53, 38.2%) received standard treatment CHOP-21 (n = 28) or R-CHOP-21 (n = 25). Results. A complete remission without recurrences was achieved in all 53 patients without signs of unfavourable prognosis (100%). Overall 5-year survival was 96%, 2 patients died in remission of other causes. Of 86 patients with a poor prognosis a complete remission was achieved in 64 (74.4%) patients. Overall and recurrence-free 5-year survival was 65 and 86%, respectively. Conclusion. Standard treatment provided long-term complete remission in all the patients without poor prognosis. Intensive (mNHL-BFM-90) treatment produced the best results in generalized lesion without BM involvement. Overall 5-year survival was 84% in these patients and 12% in patients with BM involvement.

A male patient received non-chemotherapeutic drugs which induced deep neutropenia complicated with sepsis, bilateral pneumonia, acute respiratory insufficiency. Artificial pulmonary ventilation was applied. The examination of bronchoalveolar lavage showed the presence of the culture L. pneumophila (serogroup 1) in a concentration 2x103 CFU/ml. Antibacterial therapy with levofloxacin in a dose 1000 mg/day was conducted. In a week not only L.pneumophila but also Acinetobacter baumanii was isolated from bronchoalveolar lavage. Tigecyclin was added to levofloxacin treatment. Two air cavities were found in the left lung. The treatment reduced the size of these cavities, infiltrative changes in the lungs and respiratory insufficiency regressed. The patient was discharged from hospital. This case is the first case in Russia of L.pneumophila isolation from bronchoalveolar lavage. The case is also characterized by use of tigecycline for treatment of combined legionella and akinetobacterial infection and cavities in the lungs in legionella pneumonia.

The article describes a rare clinical case of a patient with previously undiagnosed von Willebrand disease and basal meningioma; an intracranial neurosurgical intervention was complicated by delayed intracranial hematomas, both at the resected tumor site and distantly. The diagnosis of von Willebrand disease was established only after special hematology tests and only after surgery. Despite the use of specific therapy, the patient died due to intracranial hemorrhagic complications in the postoperative period. The paper discusses the problem of preoperative diagnosis of asymptomatic hemostasis disorders in neurosurgical patients and potential ways of its solution.Дано описание редкого клинического наблюдения: у пациента с ранее не диагностированной болезнью Виллебранда и базальной менингеомой проведенное интракраниальное нейрохирургическое вмешательство осложнилось формированием отсроченных интракраниальных гематом как на месте удаленной опухоли, так и дистантно. Диагноз болезни Виллебранда был установлен только в результате специального исследования в гематологической лаборатории и только после операции. Несмотря на применение специфической терапии, пациент погиб от интракраниальных геморрагических осложнений в послеоперационном периоде. В работе обсуждаются проблема предоперационной диагностики скрытых нарушений гемостаза у нейрохирургических больных и возможные пути ее решения.

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

The paper describes 4 cases of laparoscopic splenectomy in pregnant women with immune thrombocytopenic purpura. No complications of surgery were noted in all the patients. The postoperative period was marked by sustained clinical and hematological remission that made it possible to discontinue prednisolone therapy and to ensure an uncomplicated course of pregnancy and labor.Описано 4 случая выполнения лапароскопической спленэктомии у беременных с иммунной тромбоцитопенической пурпурой. У всех больных осложнений хирургического вмешательства не отмечено. В послеоперационном периоде получена стойкая клинико-гематологическая ремиссия, позволившая прекратить терапию преднизолоном и обеспечить неосложненное течение беременности и родов.

to study the nature of pain in hemophilic arthropathy and its prevention ways used by patients with hemophilia.A prospective, multicenter, cross-sectional study was conducted to interview 136 patients with hemophilia A or B. The survey included 32 points, including questions about drug and nondrug pain treatment, as well as questionnaires to assess the severity of pain and its impact on daily life (Brief Pain Inventory) and those to identify a neuropathic pain component (PainDetect questionnaire).83 (75%) patients with hemophilia experienced acute pain associated with bleeding into the large joints; 44 (39%) patients had chronic pain that had lasted longer than six months; 33% assessed the moderate pain experienced in the past 24 hours as severe (more than 5-8 of the 10 scores). In addition to the above, only 32% of the respondents indicated that they had painless intervals within the last 24 hours. 75% of the hemophilia patients mentioned to have limited daily activities. 74% reported their partial or complete disability when pain occurred. 77% of the respondents pointed out that when having pain, they had experienced great difficulty walking. 55% of the hemophilia patients had sleep disorders because of pain. When acute pain occurred, only 91 (81%) respondents injected a factor VIII or IX preparation, 37% of the respondents used narcotic analgesics; 51% received different nonsteroidal anti-inflammatory drugs; 13% took paracetamol. Some patients indicated that they used alcohol and illegal narcotic drugs to relieve pain. Attention is drawn to the fact that the hemophilia patients very frequently took painkillers: 60% of the respondents used analgesics every month; of them 49% had them every week, 11% every day. Most patients (n=83 (74%)) stated that they treated pain (prescribed drugs) themselves; 49 (44%) patients held they were dissatisfied with their pain treatment. When the question as to how the analgesic you used could "remove' pain was asked, only 12 (10%) patients answered that this could fully relieve the pain; 31 (26%) patients told that the pain was not reduced even by half. The study has shown that a neuropathic pain component is very common in hemophilia patients (31%).Pain in patients with hemophilia is a serious problem that negatively affects their quality of life, including their working capacity. The prevention and treatment of pain in hemophilia patients should involve the following: organization of educational activities and pain services; adequate treatment of acute pain; detection and prevention of a neuropathic pain component.Цель исследования. Изучение характера боли при гемофилической артропатии, способов ее преодоления, используемых пациентами с гемофилией. Материалы и методы. Проведено проспективное, многоцентровое, одномоментное исследование, в ходе которого опрошены 136 пациентов, страдающих гемофилией А или В. Анкетирование включало 32 пункта, в том числе вопросы по медикаментозному и немедикаментозному лечению боли, по оценке тяжести боли и ее влиянию на повседневную жизнь (BPI), а также по выявлению невропатического компонента боли (PainDetect). Результаты. Острую боль, связанную с кровоизлияниями в крупные суставы, испытывают 75% (n=83) больных гемофилией; 39% (n=44) страдают от хронической боли, которая длится более полугода, 33% больных гемофилией оценили среднюю боль, которую они испытывали за последние 24 ч, как тяжелую (более 5-8 из 10 баллов). При этом только 32% опрошенных указали, что ощущали промежутки времени без боли за последние сутки; 75% больных гемофилией отмечают ограничение повседневной активности; 74% больных гемофилией сообщили, что частично или полностью теряют работоспособность, когда возникает боль; 77% опрошенных указали, что, испытывая боль, отмечают большие трудности при ходьбе у 55% больных гемофилией наблюдаются нарушения сна из-за боли. При возникновении острой боли только 81% (n=91) респондентов вводят препарат фактора VIII или IX, 37% опрошенных применяют наркотические анальгетики, 51% - различные нестероидные противовоспалительные препараты, 13% - парацетамол. Некоторые пациенты указали, что для облегчения боли употребляют алкоголь и наркотические запрещенные препараты. Обращает внимание очень частый прием обезболивающих среди больных гемофилией: 60% опрошенных используют анальгетики каждый месяц, из них 49% каждую неделю, 11% каждый день. Большинство - 74% (n=83) отметили, что лечением боли (назначением препаратов) занимались самостоятельно; 44% (n=49) заявили, что недовольны результатами лечения боли. На вопрос: 'Насколько боль способен 'снять' используемый Вами анальгетик?', лишь 10% (n=12) ответили, что полностью; 26% (n=31) сообщили, что боль не уменьшается даже наполовину. Проведенное исследование показало, что у пациентов с гемофилией очень распространен невропатический компонент боли (31%). Заключение. Боль у пациентов с гемофилией является серьезной проблемой, негативно влияющей на качество жизни, в том числе работоспособность. Профилактика и лечение боли у пациентов с гемофилией должна включать следующие направления: организация образовательных мероприятий и служб боли, адекватное лечение острой боли, выявление и профилактика невропатического компонента боли.

to analyze well-known risk factors (RFs), such as age, immunophenotype, baseline leukocytosis, enhanced lactate dehydrogenase (LDH) activity, time to achieve complete remission, a risk group, and cytogenetic abnormalities) in patients with acute lymphoblastic leukemia (ALL) in the use of the ALL-2009 protocol.The protocol covered 298 patients (137 women (including 13 pregnant women) and 161 men) aged 15 to 55 years (median age 28 years) with Ph-negative ALL. The phenotype was unknown in 6 patients. Three (1%) were ascertained to have a biphenotypic variant. 182 (62.4%) patients were found to have B-cell ALL (early pre-B ALL (n=51); common ALL (n=92), and pre-B ALL (n=39); 107 (36.6%) patients had T-cell ALL (early T-ALL (n=56); thymic T-ALL (n=41), and mature T-ALL (n=10). According to the baseline clinical and laboratory parameters (leukocytosis of 30·109/l and more for B-ALL; and that of 100·109/l and more for T-ALL; phenotype В-I for B-ALL, phenotype Т-I-II-IV for T-ALL; LDH activity was more than twice the normal values; the presence of translocation t(4;11)), the high-risk group included most patients with B-ALL (n=110 (72.8%)) and T-ALL (n=76 (76%)). Thirty-five patients with T-ALL underwent autologous bone marrow transplantation (BMT). Allogeneic BMT was performed in 18 (7%) of the 258 patients who had undergone an induction phase.Five-year overall survival for all the patients included in the investigation was 59%; relapse-free survival was 65%, which was significantly different in the patients with B-ALL and in those with T-ALL: the overall survival rates were 53.3 and 67.5% (p=0.1); the relapse-free survival was 56 and 79% (p=0.005), respectively. Multivariate analysis including the well-known RFs demonstrated that the latter for T-ALL were of no independent prognostic value and only the patient's age was identified for B-ALL (p=0.013).A lower chemotherapeutic load and a small number of allogeneic BMTs did not affect total positive treatment results in adult patients with ALL, by complying with the principle achieving the continuity of cytostatic effects and by preserving the total cytostatic loading dose. The results of the Russian investigation casts some doubt on the necessity of using very intensive consolidation cycles and performing a large number of allogeneic BMTs in adult patients with ALL.Цель исследования - проанализировать общеизвестные факторы риска - ФР (возраст, иммунофенотип, исходный лейкоцитоз, повышенная активность лактатдегидрогеназы - ЛДГ, время достижения полной ремиссии, группа риска, цитогенетические аномалии) у больных острыми лимфобластными лейкозами (ОЛЛ) при использовании протокола ОЛЛ-2009. Материалы и методы. В протокол включили 298 больных Ph-негативным ОЛЛ в возрасте от 15 до 55 лет, медиана 28 лет, 137 женщин (среди них 13 беременных) и 161 мужчина. У 6 фенотип неизвестен. У 3 (1%) установлен бифенотипический вариант. У 182 (62,4%) пациентов определен В-клеточный (у 51 ранний пре-В ОЛЛ, у 92 common-ОЛЛ, у 39 пре-В ОЛЛ) и у 107 (36,6%) Т-клеточный вариант ОЛЛ (у 56 ранний Т-ОЛЛ, у 41 тимический Т-ОЛЛ, у 10 зрелый Т-ОЛЛ). К группе высокого риска на основании исходных клинико-лабораторных параметров (лейкоцитоз для В-ОЛЛ 30·109/л и более, для Т-ОЛЛ 100·109/л и более, фенотип В-I для В-ОЛЛ, фенотип Т-I-II-IV для Т-ОЛЛ, активность ЛДГ более чем в 2 раза выше нормы, наличие транслокации t(4;11)) отнесено большинство больных с В-ОЛЛ (n=110, 72,8%) и с Т-ОЛЛ (n=76, 76%). У 35 пациентов с Т-ОЛЛ осуществлена аутологичная трансплантация костного мозга (ТКМ). Аллогенная ТКМ (алло-ТКМ) выполнена лишь 18 (7%) из 258 больных, переживших индукционную фазу. Результаты. Пятилетняя общая выживаемость для всех больных, включенных в исследование, составила 59%, безрецидивная - 65%, что достоверно отличается у больных с В-ОЛЛ и Т-ОЛЛ: общая 53,3 и 67,5% (р=0,1), безрецидивная 56 и 79% (р=0,005) соответственно. Многофакторный анализ, выполненный с включением общеизвестных ФР, продемонстрировал, что для Т-ОЛЛ общеизвестные ФР не имели независимой прогностической значимости, а для В-ОЛЛ выделялся как значимый только возраст больного (р=0,013). Заключение. Снижение химиотерапевтической нагрузки и малое число алло-ТКМ не влияли на общие положительные результаты лечения взрослых больных ОЛЛ, при соблюдении принципа непрерывности цитостатического воздействия и сохранении общей дозы цитостатической нагрузки. Результаты российского исследования ставят под сомнение необходимость использования у взрослых больных ОЛЛ очень интенсивных курсов консолидации и выполнения большого количества алло-ТКМ.

The described case of FIP1L1-PDGFRА-positive myeloproliferative disease is characterized by an atypical aggressive course to develop severe specific complications as injuries to the brain, heart, lung, and intestine. Pathogenetic therapy with imatinib could stabilize a patient's state, but failed to produce a complete hematological response. Switching from imatinib to dasatinib could produce sustained clinical, hematological, and molecular remissions.Представленный случай позитивного по FIP1L1-PDGFRA миелопролиферативного заболевания отличался нетипичным агрессивным течением с развитием тяжелых специфических осложнений в виде поражений головного мозга, сердца, легких, кишечника. Патогенетическая терапия иматинибом позволила стабилизировать состояние больной, но полный гематологический ответ не получен. После замены иматиниба дазатинибом достигнута стойкая клинико-гематологическая и молекулярная ремиссия.

To estimate the informative value of ultrasonography (USG) in the diagnosis of lung injuries in pregnant women with blood system tumors.Lung ultrasound was performed in 5 pregnant patients with blood cancers. The women's age was 29-38 years; gestational age was 14-33 weeks. Four women had different types of acute leukemia; one had primary mediastinal large B-cell lymphoma. All the women received chemotherapy for blood cancer. When there were signs of lung injury, USG was conducted, the results of which necessitated therapy or bronchoalveolar lavage (BAL).Three patients developed acute respiratory failure; 2 of them required noninvasive ventilation. Based on the detection of consolidation with a dynamic air bronchogram and pleural effusion, the authors diagnosed bilateral pneumonia and alveolar-interstitial syndrome in 1 patient, right-sided pneumonia in 1, left-sided one in 1, and transfusion-related pulmonary edema in 1. Lung ultrasound did not verify the diagnosis of pneumonia in 1 patient. According to USG data, BAL procedures were performed in 2 patients; one of them was diagnosed as having Pneumocystis pneumonia; the other was found to have no pathogens in lavage fluid. Treatment resulted in clinical improvements and normalization of the lung ultrasound pattern in all the pregnant women. Later on, 4 women delivered via cesarean section done at 32-34 weeks' gestation and gave birth to healthy babies. One patient died from infectious complications after chemotherapy.Lung sound may be used to diagnose lung injury in pregnant women with blood cancers.Цель исследования. Оценка информативности ультразвукового исследования (УЗИ) в диагностике поражений легких у беременных с опухолевыми заболеваниями системы крови. Материалы и методы. Проведено УЗИ легких у 5 беременных, больных онкогематологическими заболеваниями. Возраст женщин составил 29-38 лет, срок гестации - 14-33 нед. У 4 женщин имелись различные варианты острого лейкоза, у 1 - первичная медиастинальная В-крупноклеточная лимфома. У всех женщин проводилась химиотерапия онкогематологического заболевания. При появлении признаков поражения легких выполняли УЗИ, по результатам которого назначали терапию либо выполняли бронхоальвеолярный лаваж (БАЛ). Результаты. У 3 больных развилась острая дыхательная недостаточность, у 2 из них потребовалось проведение неинвазивной вентиляции легких. На основании обнаружения консолидации, динамической бронхограммы, плеврального выпота у 1 больной диагностирована двусторонняя пневмония и альвеолярно-интерстициальный синдром, у 1 - правосторонняя, у 1 - левосторонняя пневмония, у 1 больной - трансфузионно обусловленный отек легких. У 1 больной диагноз пневмонии при УЗИ легких не подтвердился. У 2 больных по данным УЗИ выполнен БАЛ, у 1 из них диагностирована пневмоцистная пневмония, у другой патогены в лаважной жидкости не обнаружены. В результате лечения состояние улучшилось, и ультразвуковая картина легких нормализовалась у всех беременных. Позже 4 женщины родоразрешены путем кесарева сечения, выполненного на сроках 32-34 нед беременности, родились здоровые дети. Одна больная умерла впоследствии от инфекционных осложнений после химиотерапии. Заключение. УЗИ легких может использоваться для диагностики поражения легких у беременных с онкогематологическими заболеваниями.

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