Vol 91, No 7 (2019)


Russian multicenter clinical trials in acute leukemias

Parovichnikova E.N., Savchenko V.G.


The paper describes the results of 15 consecutive Russian clinical trials in the treatment of different types of acute leukemias, conducted by Russian cooperative group within the last 27-years and included more than 25 hundred patients. It was shown that the 5-years overall survival in AML younger than 60 years patients improved from 20 to 33%, in ALL - from 38 to 65%, in APL - from 0 to 95%. The cooperative work resulted in balanced clinical recommendations and protocols, reproducible in regional hospitals. Though till now there is a big difference in the long term outcome in acute leukemias patients treated in coordinating or regional centers mostly due to much higher early death rate: 7.5-9.5% vs 18-25%. This parameter should be used as criteria of the total efficacy of hematological service in each region of Russia. It became possible within the last years to integrate the minimal residual disease monitoring into clinical trials thus providing a clue parameter for choosing the further therapy - allogeneic stem cell transplantation. Non - chemotherapeutic approach with arsenic trioxide and all - trans retinoid acid had dramatically changed the toxicity and duration of treatment with very high efficacy. The Russian cooperative group was the first that started to include pregnant women with acute leukemias into clinical trials. This prospective and prolonged experience has shown that pregnancy in acute myeloid leukemia is an extremely poor prognostic factor, but it does not influence the outcome in acute lymphoblastic leukemia.
Terapevticheskii arkhiv. 2019;91(7):4-13
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Role of the intensive care in treatment of patients with acute myeloid leukemia

Bazhenov A.V., Galstyan G.M., Parovichnikova E.N., Troitskaya V.V., Kuzmina L.A., Fidarova Z.T., Gribanova E.O., Makhinya S.A., Latyshkevich O.A., Chabaeva U.A., Kulikov S.M., Savchenko V.G.


Aim. 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. Materials and methods. 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<0.05 consider as significant. Univariate analysis was performed with χ2 tests or Fisher's exact tests for categorical variables to find an independent ICU mortality predictor. Results. In total 76 pts were included. 37% of pts required admission to ICU. Reasons for the ICU admissions were: acute respiratory failure (50%), septic shock (14.3%), cerebrovascular accident (17.9%), emergency caesarian section (10.7%), cardiac arrhythmia (7.1%). There were no difference in demography, group of risk (ELN) in ICU and non-ICU pts, but in ICU pts anemia, leukocytosis were more severe. Need for vasopressors and mechanical ventilations were mortality predictors. ICU survival rate was 63.4%. A landmark analysis for overall survival (OS) was performed for patients who survived after life threatening complication in ICU group: 5-year OS - 43.2%, 5-year disease free survival (DFS) - 34%. In non-ICU group 5-yeas OS - 53%, 5-year DSF - 44% (p=0.504). Conclusion. After discharging from ICU the long - term prognosis of ICU-pts is not worse, than non-ICU pts.
Terapevticheskii arkhiv. 2019;91(7):14-24
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Somatic mutation of the V617F JAK2 gene in patients of the cardiovascular diseases

Olkhovskiy I.A., Gorbenko A.S., Stolyar M.A., Grischenko D.A., Tkachenko O.A., Martsinkevich T.L.


The JAK2 V617F somatic mutation is one of the most frequent markers of CHIP (clonal hematopoiesis of indeterminate potential). CHIP is characterized by the presence of a myeloid cells clone in peripheral blood in the absence of the sufficient reasons to diagnose the hematologic disease. The CHIP is proposed as a potential independent risk factor for vascular pathology. The aim of this study is to identify carriers of JAK2 V617F mutation among patients admitted for planned hospitalization at the Federal Center of Cardiovascular Surgery of Krasnoyarsk. Materials and methods. The study included 930 venous blood samples. JAK2 V617F mutation was detected by using the allele - specific real time polymerase chain reaction. Results. JAK2 V617F mutation was detected in 15 (1.6%) patients, but only two of them had blood cell count that could cause a hematological disease to be suspected. Conclusion. The inclusion of the JAK2 V617F mutation detection in the complex of laboratory tests of the cardiovascular patients can facilitate the timely identification of patients with increased thrombotic risk, as well as the timely diagnosis of myeloproliferative diseases.
Terapevticheskii arkhiv. 2019;91(7):25-28
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Brain MRI-findings in Ph - negative myeloproliferative disorders

Tanashyan M.M., Melikyan A.L., Kuznetsova P.I., Raskurazhev A.A., Shabalina A.A., Konovalov R.N.


Myeloproliferative disorders (MPD) are accompanied by a high proportion of thrombotic complications, which may lead to cerebrovascular disease (CVD). Aim. To describe MRI-findings in patients with Ph - negative MPD and evaluate any cerebrovascular disease. Materials and methods. We included 104 patients with Ph - negative MPD (age varied between 20 and 58) with clinical correlates of cerebrovascular pathology. Results. Brain MRI showed post - stroke lesions in 20% of patients (7 hemispheric infarcts due to thrombotic occlusion of one of the large cerebral arteries, 14 - cortical infarcts). 37 patients (36%) had vascular cerebral lesions. Cerebral venous sinus thrombosis occurred in 5 patients - in 7% (n=3) of patients with polycythemia vera and 5% (n=2) - in patients with essential thrombocythemia. The incidence of vascular cerebral lesions was associated with higher levels of the following: erythrocyte, platelet count, fibrinogen, and with the decrease in fibrinolytic activity, as well. Conclusion. The pioneering results of the study include the description and analysis of brain MRI-findings in patients with Ph - negative MPD. The underlying mechanisms of cerebrovascular pathology in these patients are associated with certain blood alterations (particularly, hemorheology) which present a major risk factor.
Terapevticheskii arkhiv. 2019;91(7):29-34
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CNS involvement and the feasibility of intratecal chemotherapy administration in patients with a nodal form of diffuse large B-cell lymphoma not otherwise specified. Data of prospective study

Magomedova A.U., Misyurina A.E., Mangasarova J.K., Gorenkova L.G., Margolin O.V., Fastova E.A., Kravchenko S.K.


Aim of the issue was to determine indications for intratecal chemotherapy drugs administration to prevent relapse of diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) involvement. Materials and methods. Since January 2009 to December 2018 102 patients with primary nodal DLBCL over 18 years old were treated in the National Research Center for Hematology, Moscow, Russian Federation. Diagnosis were established in all cases according to histological and immunohistochemical studies which made it possible to exclude the transformation of mature B-cell lymphoma into DLBCL. Results. Isolated leptomeningeal involvement of CNS in the debut of the disease was detected in 1 (0.98%) out of 102 patients with DLBCL. Focal brain tissue involvement was not detected in any patient. More than half of the patients (54%) had a high risk of disease recurrence or progression with CNS involvement: in 8 (7.8%) patients had kidney/adrenal involvement, in the same proportion - bone marrow involvement, paranasal sinuses involvement - in 5 (4.9 %), epidural space - in 7 (6.9%) and breast - in 5 (4.9%) of patients. In 82 (80%) patients, a non-GCB (postgerminal differentiation of B-cell analog) molecular subtype of DLBCL was determined. Conclusion. The introduction of chemotherapy drugs into the spinal canal is recommended in isolated cases of leptomeningeal involvement of CNS at the time of DLBCL onset and is carried out according to standard recommendations. Prevention of relapse with involvement of central nervous system using intratecal chemotherapy in patients with nodal form of DLBCL is not indicated due to the absence of cases with disease progression or recurrence into CNS when patients were treated with R-m-NHL-BFM-90, R-DA-EPOCH and R-CHOP protocol.
Terapevticheskii arkhiv. 2019;91(7):35-40
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Risk - adapted intensive induction therapy, autologous stem cell transplantation, and rituximab maintenance allow to reach a high 7-year survival rate in patients with mantle cell lymphoma

Vorobyev V.I., Gemdzhian E.G., Dubrovin E.I., Nesterova E.S., Kaplanov K.D., Volodicheva E.M., Zherebtsova V.A., Kravchenko S.K.


Mantle cell lymphoma (MCL) is aggressive B-cell neoplasm diagnosed predominantly among older men. R-CHOP-like regimens allow to achieve high response rate, but the overall survival (OS) are disappointingly short - 3-4 years. An addition of high - dose cytarabine to the upfront therapy and autoSCT significantly improved outcomes but remain feasible largely for medically fit patients. Based on the activity and good tolerance of gemcitabine - oxaliplatin schemes in relapsed and refractory MCL patients, we developed an alternative first - line course for patients who are not eligible for R-HD-MTX-AraC. Aim. Assess toxicity and efficacy of R-DA-EPOCH/ R-HD-MTX-AraC and R-DA-EPOCH/R-GIDIOX schemes, autoSCT and R-maintenance in untreated MCL patients. Materials and methods. 47 untreated MCL patients from 6 centers were enrolled in prospective study between April 2008 and September 2013. All patients have stage II-V; ECOG 0-3; median age 55 years (29-64); Male/Female 76%/24%. MIPIb: 28% low, 33% intermediate and 39% high risk. Following 1st R-EPOCH patients were assigned to receive either R-DA-EPOCH/ R-HD-MTX-AraC or R-DA-EPOCH/ R-GIDIOX regimen. In the absence of renal failure, hematological toxicity grade 4 more than 3 days and severe infections patients received R-HD-MTX-AraC scheme (R 375 mg/m2 Day 0, Methotrexate 1000 mg/m2/24 hours Day 1, AraC 3000 mg/m2 q 12 hrs Days 2-3). Patients who had at least one of these complications received R-GIDIOX scheme (R 375 mg/m2 day 0, gemcitabine 800 mg/m2 days 1 and 4, ifosfamide 1000 mg/m2 days 1-5, dexamethasone 10 mg/m2 IV days 1-5, irinotecan 100 mg/m2 day 3, oxaliplatin 120 mg/m2 day 2). Subsequently these courses were alternating with R-DA-EPOCH in each arm of the protocol. Depending on the time of achieving CR patients received 6 or 8 courses, unless they progressed on therapy. Those patients who achieved PR/CR/CRu underwent autoSCT (BEAM-R). Post - transplant R-maintenance was administered for 3 years (R - 375 mg/m2 every 3 months). Results. 29/47 patients were treated on R-HD-MTX-AraC arm (median 50 years; MIPIb: 35.7% low, 28.6% intermediate, 35.7% high risk) and 18/47 patients were on R-GIDIOX arm (median 60 years; MIPIb: 16.7% low, 38.9% intermediate, 44.4% high risk). In R-HD-MTX-AraC arm CR rate was 96.5%. In R-GIDIOX arm OR and CR rates were 94.4% and 77.7% respectively. Main hematological toxicity of R-GIDIOX was leukopenia gr. 4 occurred in 74.1%. With median follow - up of 76 months, the estimated 7-years OS and EFS in R-HD-MTX-AraC arm are 76% and 57% respectively. In R-GIDIOX arm the estimated 7-years OS and EFS are 59% and 44%, respectively. There are no statistical differences in EFS (p=0.47) and OS (p=0.06) between two arms. Conclusions. The use of a risk - adapted strategy allowed 95.7% of patients achieve PR/CR/CRu, performed autoSCT and begun R-maintenance therapy with rituximab. None of the patients needed a premature discontinuation of therapy because of unacceptable toxicity. The performance of autoSCT and R-maintenance apparently allowed to partially offset differences in the intensity of induction therapy and to maintain comparable results of therapy in both induction arms.
Terapevticheskii arkhiv. 2019;91(7):41-51
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The role of translocations involving c-MYC/8q24, BCL2/18q21 and/or BCL6/3q27 genes in patients with follicular lymphoma. Retrospective analysis of single - centre data

Misyurina A.E., Kravchenko S.K., Kovrigina A.M., Magomedova A.U., Plastinina L.V., Obukhova T.N., Misyurin A.V., Misyurin V.A., Grebenuk L.A., Babaeva F.E., Baryakh E.A., Vorobiev A.I.


Aim of the issue was to compare clinical characteristics and treatment results of patients with follicular lymphoma (FL) with translocations involving loci of c-MYC/8q24, BCL2/18q21 and/or BCL6/3q27 genes and patients with high - grade B-cell lymphoma [High - grade B-cell lymphoma (HGBL), double - hit (DH)]. Materials and methods. Since 2004 to 2017 years in National Research Center for Hematology 12 patients with high - grade B-cell lymphoma double - hit (HGBL DH) and 6 FL patients with translocations involving c-MYC and BCL2 and/or BCL6 had been treated. We performed a comparative analysis of clinical characterisctics in both groups. As primary endpoints was assessed frequency of complete remission (CR) or progressive disease (PD); as secondary endpoints - overall (OS) and event - free survival (EFS). Results. 5 patients with HGBL DH had c-MYC/BCL6, 7 - c-MYC/BCL2 rearrangements; 2 patients with FL had c-MYC/BCL2, 3 - c-MYC/BCL6, 1 - c-MYC/BCL2/BCL6 rearrangements. FL was represented by grade 3A in 2, grade 3B - in 4 cases, 3 of them had large - cell transformation. In HGBL DH and FL patients had no significant differences in clinical characteristics. The majority of patients had a widespread tumour, increased LDH activity, high frequency of extranodal and bone marrow involvement. Ki-67 expression level was lower in patients with FL (p<0.05). Patients with HGBL DH were treated with R-BL-M-04, R-(DA)-EPOCH, CHOP-21±R, with FL - R-CHOP-21 or R-(DA)-EPOCH. Frequency of CR in HGBL DH and FL was 42% and 33%, respectively. Frequency of PD was 50% in both groups. Two - year OS of patients with HGBL DH and FL harbouring c-MYC, BCL2 and/or BCL6 rearrangements was 50% and 42% respectively, p=0.85. Two - year EFS was 33% in both groups, p=0.8. Conclusions. We presented highly aggressive variant of FL grade 3 harbouring c-MYC, BCL2 and/or BCL6 rearrangements that had similarly poor prognosis as patients with HGBL DH.
Terapevticheskii arkhiv. 2019;91(7):52-62
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Molecular diagnosis angioimmunoblastic T-cell lymphoma

Chernova N.G., Sidorova Y.V., Smirnova S.Y., Ryzhikova N.V., Nikulina E.E., Kovrigina A.M., Sinitsyna M.N., Sudarikov A.B.


Aim: to determine molecular diagnostics routine for different tissue samples in angioimmunoblastic T-cell lymphoma. Materials and methods. Molecular studies were performed for 84 primary AITL patients. The median age was 61 year (29-81); the male to female ratio was 48/36. T-cell and B-cell clonality was assessed by GeneScan analysis of rearranged T-cell receptor (TCRG, TCRB) and immunoglobulin heavy chain genes. For the quantitative determination of cells with RHOA G17V mutation real - time polymerase chain reaction (PCR) with allele - specific LNA modified primers was used. Results. In lymph nodes rearrangements of T-cell receptor genes were determined in 76 (90.5%) of 84 patients and were absent in 8 (9.5%) cases. Identification of the same clonal products of the TCRG and TCRB genes in the lymph node and in peripheral blood and/or bone marrow indicated the prevalence of the tumor process and was observed in 64.7% of patients. Clonal products in peripheral blood and/or bone marrow different from those in the lymph node indicated reactive cytotoxic lymphocyte population and were noted in 58.8% of AITL cases. Simultaneous detection of T- and B-cell clonality in the lymph node was observed in 20 (24.7%) of 81 patients. Cells with RHOA G17V mutation were detected in lymph node in 45 (54.9%) of 82 patients. The use of allele - specific PCR with LNA modified primers revealed presence of the tumor cells in peripheral blood in 100% and in bone marrow in 93.9% of patients with G17V RHOA mutation in the lymph nodes. Conclusion. The validity of different molecular assays performed on certain tissue samples for the diagnosis of angioimmunoblastic T-cell lymphoma has been evaluated. Quantitative allele - specific PCR assay for RHOA G17V mutation based on LNA modified primers possesses sufficient sensitivity for tumor process prevalence evaluation and minimal residual disease monitoring.
Terapevticheskii arkhiv. 2019;91(7):63-69
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Difficulties evaluating hematological response in patients with multiple myeloma and dialysis - dependent renal impairment

Rekhtina I.G., Mendeleeva L.P., Soboleva N.P.


Aim: to determine serum free light chains (FLC) level by patients with multiple myeloma (MM) and dialysis - dependent renal impairment in which the amount Bence Jones (BJ) protein in the urine met the criteria of hematological response. Patients and methods: This study included 13 MM with dialysis - dependent renal impairment patients (estimated glomerular filtration rate < 10 ml/min), whose urine BJ protein content was less than 200 mg/day after antimyeloma therapy (including 11 patients whose urine BJ protein content was less than 100 mg/day). Results. The median serum concentration of monoclonal FLC was 608.7 (298-8380) mg/l. Thus, with trace amounts BJ protein in the urine serum content monoclonal FLC varied 28 times with the same degree of severity of renal failure. In patients with oliguria serum SLC content was significantly higher than in normal diuresis (1109 and 307 mg/L; p<0.05). Conclusion. Low amount of BJ protein in urine of patients with MM and dialysis - dependent renal impairment can be combined with high concentration of monoclonal FLC in serum. Therefore, the study of FLC in serum is necessary for monitoring MM in this group of patients. It is important to develop clarifying criteria of hematological response in patients with MM and dialysis - dependent renal impairment.
Terapevticheskii arkhiv. 2019;91(7):70-74
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PET/CT with 18F-fluorodeoxyglucose and 11C-methionine after autologous stem cell transplantation in multiple myeloma patients

Solovev M.V., Mendeleeva L.P., Firsova M.V., Aslanidi I.P., Mukhortova O.V., Savchenko V.G.


Aim: to compare the results of tumor visualization when using 18F-FDG and 11C-methionine PET/CT after auto-HSCT in MM patients. Materials and methods. A prospective study included 27 MM patients subjected to 18F-FDG and 11C-methionine PET/CT on day 100 after auto-HSCT. Obtained images were visually and semi - quantitatively analyzed. Focal areas of increased uptake for every radiopharmaceutical agent (hypermetabolic foci) not associated with its physiological distribution were registered. Maximum Standardized Uptake Values (SUVmax) in pathological foci were automatically calculated for every radiopharmaceutical agent separately. PET/CT findings were compared to antitumor response achieved after auto-HSCT according to International MM Working Group criteria. Results. After auto-HSCT, the majority of patients (16/60%) achieved a complete response. Abnormal 18F-FDG uptake was registered in 37% (n=10) of patients, negative PET findings were obtained in 63% (n=17) of patients. 11C-methionine PET/CT revealed hypermetabolic foci in 67% (n=18) of patients, and there was no 11C-methionine uptake in 33% (n=9). Pathological foci of radiopharmaceutical agent uptake were 1.8 times more frequently revealed using PET/CT with 11C-methionine (p<0.02). The mean SUVmax for 18F-FDG was 1.02, whereas the mean SUVmax for 11C-methionine was 2.29. The SUVmax value for 11C-methionine significantly exceeded that for 18F-FDG (р=0.02). Conclusion. 11C-methionine PET/CT was superior to 18F-FDG overcoming its limitations and increasing the tumor detection rate in bone marrow in MM patients after auto-HSCT.
Terapevticheskii arkhiv. 2019;91(7):75-82
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Epidemiology of multiple myeloma in city Moscow

Vinogradova O.Y., Ptushkin V.V., Chernikov M.V., Kochkareva Y.B., Zherebtsova V.A.


Aim. To study the epidemiology of multiple myeloma in the city of Moscow and compare the results obtained with data from similar studies in other countries. Materials and methods. The study is based on information from a database of case histories of 3942 patients suffering from symptomatic MM, residents of the city of Moscow, which is maintained at the Hematologic Moscow City Center of S.P. Botkin Municipal Clinical Hospital. The control of the completeness of inclusion was carried out by cross - comparison with the data of the Moscow Cancer Register and the Register of Program 7 (beginning in 2019 - 12) of Highly Expensive Nosologies. The assessment was made according to data as of January 1, 2019. The calculations were carried out taking into account the data of Rosstat at the beginning of 2019 on the population of Moscow in different gender and age categories. Results. Among the 3942 patients with active MM 1707 men - 43% and 2241 women - 57%, the median of the current age was 68 (28-94) years. The median time of observation of patients since the diagnosis of the disease 34 (1-423) months. The peak incidence was in the age range of more than 60 years. There were no significant differences in gender ratio in different age strata with a breakdown of 10 years. The number of cases of newly diagnosed MM per year for the period from 2009 (n=219) to 2018 (n=385) increased by 75.8%. At the same time, the demonstrated increase in the incidence rate for the described period turned out to be fair only for groups of patients over 50 years old, with the maximum increase in this indicator over the described period in the age range of 60-69 years. This is mainly due to the increase in life expectancy in Moscow in recent years. The study demonstrated that over the past 10 years, the average annual mortality rate from MM has decreased in Moscow, and as a result, its prevalence has increased. The rate of 2-year overall survival of patients with MM was 76%, 5-year - old - 49%, 10-year - old - 27%. The median overall survival of patients under the age of 65 when diagnosing the disease was 79 months, and 48 months. The distribution of patients within international classifications was consistent with international data. Conclusions. The study revealed a significant dynamic of the epidemiological situation concerning MM in Moscow. Over the past 10 years there has been an increase in the incidence of MM, as a result of an increase in the life expectancy of the population. The use of modern diagnostics and therapy of MM in real clinical practice has led to a significant reduction in mortality. Due to these factors, an increase in the prevalence of MM in Moscow has taken place, and this process will no doubt progress in the future.
Terapevticheskii arkhiv. 2019;91(7):83-92
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Clinical features and diagnosis of Ph - negative myeloproliferative neoplasms occurring in conjunction with the antiphospholipid syndrome

Melikyan A.L., Subortseva I.N., Koloshejnova E.A., Gilyazitdinova E.A., Shashkina K.S., Gorgidze L.A., Tratsevskaya Z.V., Margolin O.V.


Thrombosis is a serious and extremely dangerous disease that has a negative impact on the quality and longevity. Antiphospholipid syndrome (APS) is a pathology characterized by recurring venous, arterial, microvasculature thrombosis, pregnancy pathology with loss of the fetus and the synthesis of antiphospholipid antibodies. A high risk of thrombotic complications is also observed in patients with myeloproliferative neoplasms (MPN). This article presents a description of three clinical cases of Ph - negative myeloproliferative diseases, occurring in conjunction with APS. In all cases, recurrent thrombosis allowed to suspect the presence of two diseases - MPN and APS.
Terapevticheskii arkhiv. 2019;91(7):93-99
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Clinical case of IgG4-related disease in a patient with Burkitt lymphoma

Feydorova T.I., Vinokurova L.V., Dvoynikov S.Y., Mikheeva O.M., Dudin G.A., Akopova A.O.


The article provides a case of primary diagnosis of IgG4-related disease in a patient with Burkitt lymphoma.
Terapevticheskii arkhiv. 2019;91(7):100-105
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Clinical observation of a patient with thrombotic thrombocytopenic purpura with renal and intestinal lesions

Stolyar A.G., Avdonin P.V., Valamina I.E., Stolyarevich E.S.


The article presents a brief description of a rare disease - thrombotic thrombocytopenic purpura (Moshkovits - disease), which is based on the deficiency of ADAMTS-13 metalloproteinase, leading to the development of thrombotic microangiopathy with the defeat of vital organs. The article also describes the clinical observation of a patient with the Moshkovits - disease. The features of the above observation are involvement in the pathological process of the kidneys and intestines, while in the classical descriptions of the disease there is a predominant lesion of the Central nervous system, as well as the genetic form of the disease.
Terapevticheskii arkhiv. 2019;91(7):106-110
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Personalized approach for direct oral anticoagulant prescription: from theory to practice

Skripka A.I., Kogay V.V., Listratov A.I., Sokolova A.A., Napalkov D.A., Fomin V.V.


Data on possibilities of personalized approach for direct oral anticoagulants (DOAC) choice in patients with atrial fibrillation are presented in the article. We also review clinical and fundamental studies and future perspectives on pharmacogenetic and pharmacokinetic tests to predict the efficacy and safety of DOAC.
Terapevticheskii arkhiv. 2019;91(7):111-120
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Pure red cell aplasia of the bone marrow in combination with thymoma. A literature review and own data

Petrenko A.A., Pivnik A.V., Dudina G.A., Dubnitskaya M.G.


Eight patients were observed with a rare combination of thymoma and pure red cell aplasia of bone marrow (PRCA), of which seven women were between 44 to 68 years old. The diagnosis of PRCA was established before the detection of thymoma in 1 patient, simultaneously in 3, after - in 4. Seven patients underwent timomectomy. The weight of removed thymomas was from 200 to 780 grams. Morphological type A thymoma variant (spindle cell) was installed in 2 patients, type B1 - in 2, type B2 - in 2, type B3 - in 2. Complete remissions were obtained using cyclophosphamide and cyclosporin in 5 patients, lasting from 6 months to 7 years. The results of immunological studies with the identification of non - hemolytic antibodies to the proteolytic antigen (Pr1d) on the erythrocyte membrane in 4 patients are presented. Of these, two studied patients simultaneously detected antibodies to the Pr1d antigen and the interspecific antigen of mammalian erythroblasts (IAME). It is shown that the lifespan of red blood cells are not changed. The direct Coombs test was negative in 5 patients, but with the help of aggregate hemaglutination test and enzyme immunoassay, antibodies were detected on the surface of erythrocytes. The pathogenesis of this combination of diseases remains unclear and needs to be elucidated.
Terapevticheskii arkhiv. 2019;91(7):121-126
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Enzyme replacement therapy in adult patients with type I Gaucher disease

Ponomarev R.V., Lukina E.A.


Enzyme replacement therapy (ERT) is the standard for the treatment of Gaucher disease (GD). A lifelong intravenous administration of a recombinant analogue of human glucocerebrosidase compensates for the functional deficiency of its own enzyme. The use of ERT has changed the clinical phenotype of GD, a severe progressive disease has been turned into the status of an asymptomatic metabolic defect. At the same time, a reduced dosing ERT regimen applied in Gaucher patients who had achieved therapeutic goals has not yet been developed.
Terapevticheskii arkhiv. 2019;91(7):127-131
pages 127-131 views

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