Helicobacter pylori infection is widespread worldwide. It plays a signifi cant role in the pathogenesis of many diseases of the gastrointestinal tract, such as peptic ulcer, atrophic gastritis, and cancer of the stomach. Recently, a large number of works have appeared that indicate the association of Helicobacter pylori infection with extragastric diseases. Liver diseases, and especially fatty liver disease, are also widespread and actively studied. The association between Helicobacter pylori infection and non-alcoholic fatty liver disease has been the subject of many studies, but there is still insufficient evidence to make it clear.

Purpose of the study. Compare the effectiveness of different eradication therapy regimens in patients with chronic pancreatitis with concomitant gastritis associated with various genetic variants of H. pylori.Materials and methods: 63 patients with chronic pancreatitis and concomitant Helicobacter pylori-associated gastritis were examined. The control group consisted of 45 patients with chronic gastritis. Diagnosis of chronic pancreatitis was based on anamnestic, clinical data, instrumental studies (MSCT). Diagnosis of H. pylori infection was carried out by the morphological method, 13C urease breath test, and immunoblotting. Statistical processing was carried out using application packages SPSS Statistic 17.0.Results. In patients with chronic pancreatitis, CagA-positive H. pylori strains were found 19.3% less often compared with the control group (p <0.05), VacA-positive—21.9% less often (p <0.05). In the study group, H. pylori genes encoding urease A production and genes encoding the synthesis of H. pylori outer membrane proteins (p33, p30, p29, p26, p19, p17) were significantly more frequently met. In the group of patients with chronic pancreatitis, the standard triple therapy of the 1st line with the inclusion of bismuth tripotassium dicitrate was 86.8% more effective (p <0.01) compared to the standard triple therapy of the 1st line, and the maximum increase in efficiency was observed among owners of H. pylori strains, expressing urease A and with the representation on the outer membrane of the proteins p30, p33, p26, p19, p17 (p <0.01).Conclusion. Eradication therapy in patients with chronic pancreatitis in the presence of pathogenicity complex p30, p33, urease A, p26, p19, p17 in H. pylori according to the standard line triple therapy protocol with the inclusion of bismuth tripotassium dicitrate has advantages compared to the standard triple therapy protocol 1 line (p <0.001).

Relevance. Currently, there is a need to study the genetic diversity of H.pylori in patients with variety of acid-related diseases to develop new strategies for the treatment of patients with H.pylori to predict high efficiency of treatment. Objective: To assess the effectiveness of schemes of eradication therapy in patients with chronic pancreatitis and concomitant H.pylori infection. Materials and methods. The study included 108 patients with H.pylori infection: 63 patients had chronic pancreatitis and were concomitant with H.pylori-infection and 45 patients were without chronic pancreatitis and had H.pylori infection with a chronic gastritis. All patients were determined by factors of pathogenicity of H.pylori by immunoblotting. After forming the group randomized patients received eradication therapy scheme I and the scheme I with inclusion of bismuth tripotassium dicitrate. Conclusions. The effectiveness of H.pylori eradication therapy is dependent on the genetic component of H.pylori. In the presence of H.pylori pathogenicity factors p33, p30, p26, p19, p17 in order to increase the effectiveness of treatment the scheme of eradication therapy I line drugs bismuth tri dicitrate should be included.

RELEVANCECurrently, there is a need to study the genetic diversity of H.pylori in patients with variety of acid-related dis- eases to develop new strategies for the treatment of patients with H.pylori to predict high efficiency of treatment.OBJECTIVETo assess the effectiveness of schemes of eradication therapy in patients with chronic pancreatitis and concom- itant H.pylori infection.MATERIALS AND METHODSThe study included 108 patients with H.pylori infection: 63 patients had chronic pancreatitis and were concomitant with H.pylori-infection and 45 patients were without chronic pancreatitis and had H.pylori infection with a chronic gastritis. All patients were determined by factors of pathogenicity of H.pylori by immunoblotting. After forming the group randomized patients received eradication therapy scheme I and the scheme I with inclusion of bismuth tripotassium dicitrate.CONCLUSIONSThe effectiveness of H.pylori eradication therapy is dependent on the genetic component of H.pylori. In the presence of H.pylori pathogenicity factors p33, p30, p26, p19, p17 in order to increase the effectiveness of treatment the scheme of eradication therapy I line drugs bismuth tri dicitrate should be included.

Objective. To assess treatment outcomes of 132 patients with acute myeloid leukemia (AML) treated in hematology department of the N.N. Blokhin Russian Cancer Research Center over the period from January, 2003, till November, 2014. Methods. 106 patients with primary AML and 26 patients with secondary AML and AML arising from MDS were enrolled in this study. Median age was 43.5 years (varied from 15 to 82). The study design provided 1 cycle of remission induction according to the 3+7+7 scheme (idarubicin 12 mg/m 2 on days 1-3, cytarabine 100 mg/m 2 every 12 h on days 1-7, etoposide 75 mg/m 2 on days 1-7), 2 cycles of consolidation according to the HAI scheme (cytarabine 3 g/m 2 on days 1, 3, 5; idarubicin 10 mg/m 2 on days 2, 4), and 6 cycles of maintenance treatment according the 1+5+5 scheme for patients younger than 60 years (cytarabine 100 mg/m 2 every 12 h on days 1-5, idarubicin 15 mg/m 2 on day 1, etoposide 75 mg/m 2 on days 1-5). The treatment protocol for patients aged 60-65 did not include etoposide, and the cytarabine dose was reduced to 1 g/m 2 at the remission consolidation stage. Results. The analysis of treatment efficacy in 71 patients younger than 60 years with primary AML demonstrated that the percentage of complete remissions (CR) was 77.5 %. In 41 (74.5 %) patients the CR was achieved after the 1st induction cycle. The 5-year overall survival (OS) and relapse-free survival (RFS) rates were 43 % and 52 %, respectively. In the favorable cytogenetic risk group, the CR rate was 90 %, 5-year ОS and RFS were 65 % and 100 %, respectively; in the intermediate cytogenetic risk group these parameters were 90.5 %, 45 %, and 48 %, respectively. In the high risk group, CR was achieved in 36.4 % patients achieved; the resistant disease was observed in 63.6 % of cases, 2-years ОБ and DFS rates were 16 % and 0 %, respectively. Among patients aged 60-65 years receiving intensified consolidation therapy, the CR rate was 61.5 %, the resistant disease was observed in 23.1 % of cases. The early mortality rate was 15.4 %, and the 3-year ОБ and DFS rates were 14 % and 50 %, respectively. Conclusion. The treatment program with intensified consolidation demonstrated high long-term survival rates in patients with primary AML younger than 60 years. The best results were obtained in the favorable cytogenetic risk group. Management of patients over 60 years of age and patients with AML in high-risk cytogenetic group is still a challenge.

Резюме Цель исследования. Оценить эффективность высокодозной терапии по протоколу ДВККЛ-ЦНС-2007 у больных диффузной В-крупноклеточной лимфомой (ДВККЛ) с поражением яичка. Материалы и методы. Из 408 пациентов мужского пола с неходжкинской лимфомой в исследование включено 8 больных ДВККЛ с первичным вовлечением яичка (у 3) или с генерализованной стадией ДВККЛ, у которых клиническая картина дебютировала с поражения яичка (у 5) в возрасте от 50 до 69 лет (медиана возраста 55,5 года). Данные пациенты наблюдались с 2007 по 2013 г. в ФГБУ «Гематологический научный центр» (ГНЦ) Минздрава России. Системная химиотерапия проводилась согласно протоколу ДВККЛ ЦНС-2007. Результаты. В первой линии терапии протокол ДВККЛ ЦНС-2007 выполнен у 7 пациентов. Одному пациенту на первом этапе диагностики установлен диагноз анапластической семиномы, в связи с чем произведена орхифуникулэктомия справа и в дальнейшем проведена лучевая терапия на область мошонки в суммарной очаговой дозе 34 Гр. В рецидиве заболевания данный пациент включен в протокол лечения ДВККЛ ЦНС-2007. Количество курсов ПХТ (4 или 6) определялось периодом достижения полной ремиссии. После завершения полихимиотерапии по схеме ДВККЛ-ЦНС-2007 полная ремиссия достигнута у 6 пациентов, в 2 случаях отмечалось первично-резистентное течение заболевания. В настоящий момент 6 пациентов живы в первой полной ремиссии при медиане наблюдения 50 (10—54) мес. Заключение. Полученные результаты позволяют предположить, что терапия в высоких дозах согласно протоколу ДВККЛЦНС-2007 у больных ДВККЛ с поражением яич ка позволяет достичь полной ремиссии заболевания, увеличить общую и «бессобытийную» выживаемость пациентов. Для подтверждения данного факта необходимо большее количество наблюдений.

Clonal disorders of karyotype are detected in half of patients with the myelodysplastic syndrome (MDS. Bone marrow cell karyotype is an independent prognostic factor for risk stratification and choice of treatment strategy. Conventional cytogenetic analysis (CCA) do not always give complete information about chromosome abnormalities in MDS patients. The efficiency of fluorescent in situ hybridization (FISH) in addition to CCA, detecting latent abnormalities of karyotype in MDS, is demonstrated. A clinical case is presented: a female patent with 5q deletion, which could not be detected by CCA.

The additional molecular and chromosomal abnormalities (ACA) in Phositive cells usually considered as a genetic marker of chronic myeloid leukemia (CML) progression. 457 patients in different CML phases received tyrosine kinase inhibitors (1st and 2nd generation) were studied. During therapy 50 cases with additional chromosomal abnormalities in Ph+ clone (22 of them in chronic CML phase) were revealed (median follow-up from CML diagnosis – 117 months, median imatinib therapy – 62 months). 86 % of patients in chronic phase with Ph+- cell abnormalities were cytogenetic resistance, and their 5-years overall survival was 80 % which was significantly lower than in patients without ACA (p < 0.005). The treatment results depend on chromosomal abnormalities detected. In patients with additional chromosome 8 imatinib therapy is effective, although complete cytogenetic response (CCR) is achieved only in the later therapy stages. In patients with additional translocations CCR also achieved with imatinib or 2nd generation TKI. Only a third of patients with additional Ph-chromosome or BCR/ABL amplification achieved complete suppression of Ph+ clone using 2nd generation TKI. The presence of additional chromosome 7 abnormalities and complex karyotype disorders involving isochromosome i(17)(q10) are poor prognostic factors of TKI treatment failures.

AIM:To evaluate the efficiency of high-dose therapy according to the DLBL-CNS-2007 protocol in patients with testicular diffuse large B-cell lymphoma (DLBL).SUBJECTS AND METHODS:Out of 408 male patients with non-Hodgkin lymphoma, 8 patients aged 50 to 69 years (median age 55.5 years) with primary testicular (n=3) or with generalized-stage testicular DLBL (n=5) were included in the study. These patients were followed up at the Hematology Research Center, Ministry of Health of the Russian Federation, in 2007 to 2013. Systemic chemotherapy was performed in accordance with the DLBL-CNS-2007 protocol.RESULTS:The DLBL-CNS-2007 protocol was implemented in first-line therapy in 7 patients. At the first diagnostic stage, one patient was found to have anaplastic seminoma; in this connection right orchifuniculectomy was carried out, followed by radiotherapy applied to the scrotal region in a total focal dose of 34 Gy. This patient with disease recurrence was included in the DLBL-CNS-2007 treatment protocol. The number of polychemotherapy (PCT) cycles (n=4 or 6) was determined by the time to achieve complete remission. After completion of DLBL-CNS-2007 PCT, 6 patients achieved complete remission; the primary resistant disease was noted in 2 cases. At this moment 6 patients are alive in first complete remission during the median follow-up of 50 months (10-54 months).CONCLUSION:The findings suggest that high-dose therapy according to the DLBL-CNS-2007 protocol in patients with testicular DLBL can achieve complete remission and increase overall and event-free survival rates. This fact should be borne out by a large number of observations.

Clonal disorders of karyotype are detected in half of patients with the myelodysplastic syndrome (MDS. Bone marrow cell karyotype is an independent prognostic factor for risk stratification and choice of treatment strategy. Conventional cytogenetic analysis (CCA) do not always give complete information about chromosome abnormalities in MDS patients. The efficiency of fluorescent in situ hybridization (FISH) in addition to CCA, detecting latent abnormalities of karyotype in MDS, is demonstrated. A clinical case is presented: a female patent with 5q deletion, which could not be detected by CCA.

THE PURPOSE OF THE STUDY:To study the genetic diversity of H. pylori in patients with chronic gastritis, peptic ulcer disease, chronic pancreatitis.MATERIALS AND METHODS:The study involved 490 patients with gastric ulcer, duodenal ulcer, chronic superficial gastritis, chronic atrophic gastritis, chronic pancreatitis. Diagnosis of H. pylori infection was carried out by the following methods: morphological, urea breath test serological (determining the concentration of IgG antibodies to H. pylori and immunoblotting) and by polymerase chain reaction. For genotyping of H. pylori using sets of primers with a mixture of CagA, VacA s1/ s2, VacA m1, VacA m2, IceA1, IceA2, BabA. To perform immunoblotting using Anti-Helicobacter pylori EUROLINE-Western blot (IgG), based on the Western blot method using test strips with antigens separated by electrophoresis cell extract H. pylori. Statistical computer processing was performed using software packages Statistic for Windows 6.0.RESULTS:The virulent genotype of H. pylori was determined in 92% cases of duodenal ulcer. In chronic non-atrophic and atrophic gastritis virulent genotypes of H. pylori were not detected. In case of uncomplicated duodenal ulcer we revealed isolated (vacA m2) and combined (vacA s1/ s2) genotypes of H.pylori in 23% of cases, of them monogenotip VacAm2 (vacuolating-associated cytotoxin) was determined in 83%. In complicated duodenal ulcer the combined genotype of H. pylori (vacAs1/ s2; vacAs1/ s2 + vacAm1 + vacAm2; vacAs1/ s2 + vacAm2) and mixed genotype of H. pylori (vacAs1/ s2 + cagA, vacAs1/ s2 + iceA2, vacAm1 + cagA + iceA2) were determined in 77% of the samples. In cases of chronic pancreatitis the vacuolating cytotoxin VacA was detected in 35.7%, such as in the control group it was 81.8%. Genes encoding the production of urease (subunit A) were found in 85.7% of chronic pancreatitis patients, in the control group--54.5%. Genes encoding the synthesis of outer membrane proteins of H. pylori such as p26, p19, p17 were detected in 82.1% of patients with chronic pancreatitis, in patients of the control group--54.5%. H. pylori outer membrane proteins with molecular weights of 30 and 33kDa (p30 and p33) were detected in 85.7% of patients with chronic pancreatitis.CONCLUSION:The bacterium H. pylori, which is the main cause of acid diseases, realizes effect through its pathogenicity factors. Waste products of H. pylori have a direct damaging effect on the mucous membrane of the stomach and duodenum, contributing to the release of lysosomal enzymes, a number of cytokines. They are cause the development of inflammatory processes in the mucosa. Lipopolysaccharide of outer membrane of H. pylori cause immune response of the human body and the development of chronic inflammation at the system level. Set of pathogenicity factors of H. pylori determine the nature and severity of the pathological processes triggered by the bacterium at different levels of the microorganism.

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

Хронический миелолейкоз (ХМЛ) — редкое заболевание, число впервые выявленных больных которым в год составляет приблизительно 1 : 100 000 населения. В Российской Федерации в настоящее время насчитывается около семи тысяч больных ХМЛ. Внедрение в течение последнего десятилетия в клиническую практику препаратов, направленно блокирующих активность опухолевой тирозинкиназы BCRABL изменило прогноз у больных ХМЛ, увеличило выживаемость больных с 3–4 лет до более 15 лет, привело к полному восстановлению трудоспособности с перспективой отмены терапии у значительной части больных. Настоящие клинические рекомендации представляют собой разработанный на основании принципов доказательной медицины протокол, включающий все этапы диагностики и терапии больных с хроническим миелолейкозом, в том числе мониторирования минимальной остаточной болезни. Предназначены для врачей-гематологов, онкологов, педиатров, организаторов здравоохранения.

Aim. To study and compare cytogenetic abnormalities in the bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic progenitor cells and in the BM mesenchymal stromal cells (MSCs) in patients with myelodysplastic syndrome (MDS).Subjects and methods. The results of a cytogenetic analysis of the total population of BM cells (BMC), CD34+ hematopoietic progenitor cells from BM and PB, and BM MSCs were analyzed in 35 patients (29 patients with MDS and 6 with MDS transformed into acute myeloid leukemia (AML)) and 7 healthy BM donors. Cytogenetic examinations were performed by G-banding of chromosomes and fluorescence in situ hybridization (FISH).Results. The BMC karyotype was abnormal in 17 (49%) of the 35 patients (13 with MDS and 4 with AML); the others were found to have a normal BM karyotype. The FISH analysis confirmed the same cytogenetic abnormalities in the BM and PB CD34+ hematopoietic progenitor cells in all the examinees with an abnormal karyotype. The mean abnormal clone sizes in the total population of BMCs and BM and PB CD34+ progenitor cells did not differ and constituted 65.8, 73.1, and 74.8%, respectively. The patients with a normal BM karyotype had no chromosome abnormalities in the CD34+ cells either. The karyotype of MSCs was analyzed in 23 (19 with MDS and 4 with AML) of the 35 patients. No karyotype abnormalities were revealed in the patients with MDS transformed into AML. There were structural chromosome aberrations in 2 (11%) of the 19 patients with MDS (one with constitutional inv(9)(p13q21) was found to have non-clonal translocation t(2;22)(p10;q11) and the other had a clone with an additional segment of the long arm of chromosome 2 in 35% of the cells. No numerical MSC karyotype abnormalities were detected. A normal MSC karyotype was defined in 7 healthy BM donors.Conclusion. The cytogenetic analysis of hematopoietic and mesenchymal progenitor cells showed that the chromosome abnormalities revealed in these cell populations were different in the patients with MDS. The isolated CD34+ cells displayed the same cytogenetic abnormalities as in a total population of BMC. Examination of the latter could reveal no cytogenetic abnormalities in the majority of the patients. A normal BMC karyotype was detectable in the patients with AML. Two (11%) patients with MDS were found to have structural chromosome abnormalities that differed from those detected in the total population of BMC and in isolated CD34+ cells. The differences of chromosome abnormalities in the hematopoietic and mesenchymal progenitor cells point to the fact that the stromal microenvironment is not part of the abnormal clone in MDS, however, it may be of great importance in the pathogenesis of the disease.

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

The incidence of unstable chromosome aberrations in peripheral blood lymphocytes from unirradiated control subjects was analyzed using cytogenetic data obtained from 9 cytogenetic laboratories located in Moscow, St.-Petersburg, Obninsk, and Dubna (Russia). The objective of this study was to estimate the level and spectrum of spontaneous chromosome aberrations in human lymphocytes. 1140 blood samples were taken from 1112 subjects (594 men and 546 women) aged 1 to 72. The total metaphase number was 466795. The uniform Giemsa method for peripheral blood lymphocyte cultures was used. After counting 466795 metaphases, 4288 chromosomal aberrations of various types were classified. The most frequent types of aberrations were acentrics and chromatid deletions. They made up 90% of the total number of aberrations. The remaining 10% were exchange aberrations. The number of chromosome exchanges (dicentrics and centric rings) was twice the number of chromatid exchanges. Overall, the portion ofcells with chromosomal or (and) chromatid aberrations was 0.89 +/- 0.01%; the frequency of acentrics was 0.29 +/- 0.01; the frequency of dicentrics was 0.046 +/- 0.003; the frequency of unstable chromosome aberrations was 0.35 +/- 0.01; and the frequency of chromatid aberrations was 0.57 +/- 0.01 per 100 cells.