[The clinical case of IgG4-related thyroid disease in a 6-year-old child].

IgG4-related disease is a rare chronic pathology manifested by lymphoplasmacytic infiltration of one or more organs, the formation of storiform fibrosis, tissue edema, and an increase of IgG4 in the blood. This disease was singled out as an independent nosological unit only in 2001. The incidence is less than 1 in 100,000 people per year. Almost any organ can be affected in IgG4-related disease. The association of Riedel's thyroiditis with IgG4 was established in 2010. Riedel's thyroiditis is an extremely rare inflammatory disease of the thyroid gland, which diagnosis is complicated by an atypical course and the absence of characteristic symptoms. Less than 300 clinical cases of the disease have been described in the world, only two from them were in children. This article presents a clinical case of a 6-year-old boy with Riedel's thyroiditis.

[Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety].

AIM: Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD). MATERIALS AND METHODS: The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR. RESULTS: After FMT higher overall bacterial mass (р=0.00088), higher bacterial numbers ofBifidobacteriumspp. (р=0.021),Escherichia coli(р=0.049) andBacteroides fragilisgr. (р=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (р=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (р=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days,p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group. CONCLUSION: FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.

[Surgical learning curve for top-down two-knot laparoscopic pyeloplasty in congenital hydronephrosis in children].

The aim was to evaluate the surgical learning curve and advantages of top-dow two-knot laparoscopic pyeloplasty in children with uretero-pelvic junction obstruction (UPJO). MATERIALS AND METHODS: A retrospective analysis of medical records regarding 98 patients from Speranskij Childrens Municipal Hospital No9, Moscow and Regional Clinical Hospital No7, Volgograd, aged from 3 to 24 months with unilateral hydronephrosis of varying degrees, according to the SFU classification (Society of Fetal Urology) in the Onen modification was carried out. LP in all children was performed in accordance with the Heins-Andersen technique, with minimal resection of the pelvis. In order to compare different techniques for the formation of pyeloureteral anastomosis, patients are divided into two groups: on the first group (n=59) TDTKT was performed, and on the second (n=39) - the standart knotting technique (SKT) was performed. The patients were operated by two surgeons from different clinics. Average time of operation, learning curves, frequency of post-operative complications and post-operative assessments were included as criteria for the comparison of the two groups. RESULTS: Using TDTKT allowed a reduction in mean time of surgery of 30%. Positive results were obtained in both groups of patients by reducing the degree of hydronephrotic transformation of the kidney during their follow-up year. CONCLUSION: Using TDTKT not only permits an experienced surgeon to reduce his duration of operation to 67.86 minutes, it also positively affects the surgical learning curve for less experienced surgeons. In this regard, this technique can be recommended to surgeons who do not have much experience in conducting laparoscopic pyeloplasty.

[Uretero-ureteral anastomosis (ureteropyeloanasto-mosis) for the duplicated upper urinary tract in children].

INTRODUCTION: The duplex kidney is one of the most common congenital abnormalities of the urinary tract, and various surgical procedures exist for the management of this condition. Depending on the surgeon preferences, patients with duplex kidney may undergo heminephrectomy with ureterectomy using open or laparoscopic approach, uretero-cysto-anastomosis of the ectopic ureter or two ureters in a single block. Recently, there have been reports of inter-ureter anastomoses. Here we report our multicenter experience in open and laparoscopic uretero-ureteral anastomosis (UUA). The study aimed to improve the treatment results in children with urodynamic dysfunction due to the duplicated upper urinary tract. MATERIALS AND METHODS: We retrospectively analyzed medical records of 64 children treated from 2007 to 2017. There were 22 (32.8%) boys and 43 (67.2%) girls with mean age 40.2 months at the time of surgery. All of them had duplex kidneys, including 27 (42.2%) right-sided and 37 (57.8%) left-sided. Of them, 15 (23.4%) children underwent distal UUA (DUAA), and 49 (76.6%) had proximal UUA (PUUA). RESULTS: After surgery, acute pyelonephritis occurred in three patients. In the early postoperative period, a prolonged urinary leakage from surgical site drainage was observed in three (6.1%) patients after laparoscopic PUUA. One (4.2%) child developed a stumpitis. Thus, complications occurred in 7 (10.9%) children; one of them (1.6%) needed additional treatment. CONCLUSION: Distal and proximal UUA is a safe and effective surgical treatment for urinary outflow disorders in patients with the duplicated upper urinary tract, minimizing the risk of the duplex kidney dysfunction.

The Role of Chromosome-Nuclear Envelope Attachments in 3D Genome Organization.

Chromosomes are intricately folded and packaged in the cell nucleus and interact with the nuclear envelope. This complex nuclear architecture has a profound effect on how the genome works and how the cells function. The main goal of review is to highlight recent studies on the effect of chromosome-nuclear envelope interactions on chromatin folding and function in the nucleus. The data obtained suggest that chromosome-nuclear envelope attachments are important for the organization of nuclear architecture in various organisms. A combination of experimental cell biology methods with computational modeling offers a unique opportunity to explore the fundamental relationships between different aspects of 3D genome organization in greater details. This powerful interdisciplinary approach could reveal how the organization and function of the genome in the nuclear space is affected by the chromosome-nuclear envelope attachments and will enable the development of novel approaches to regulate gene expression.

Diagnostics and treatment challenges of Ph-like acute lymphoblastic leukemia: a description of 3 clinical cases.

B-cell acute lymphoblastic leukemia (B-ALL) is a diverse group of malignant blood disorders both with regard to the biological properties of the tumor and to therapeutic approaches. Immunophenotyping, molecular genetic techniques, whole-genome sequencing characterize B-ALL as a very diverse group for sensitivity to chemotherapy and prognosis. We present three clinical cases of patients with B-ALL and expected good response to standard therapy, in whom standard protocol treatment failured: refractoriness, persistence of minimal residual disease (MRD), and progression (MRD increase). The remission in these patients was achieved after chemotherapy change to immunological targeted therapy. Nowadays a unified therapeutic approach to all primary patients of the B-ALL is considered generally outdated. Great efforts are carrying out to develop molecular genetic classifications. The molecular dissection of subtypes of B-ALL goes on, and new protocols for selective treatment with targeting are clearly outlined for each subtype of B-ALL.

Profiles of pro-inflammatory cytokines in allogenic stem cell transplantation with post-transplant cyclophosphamide.

Large number of studies was published about predictive value of cytokines for graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Recently, there has been a growing interest in GVHD prophylaxis with post-transplant cyclophosphamide (PTCy). Clinical data on the dynamics of proinflammatory cytokines with this prophylaxis is lacking. In this study, we have measured the levels of IL-17, IL-6, IL-8, IFN-γ and TNF-α in plasma on days -7, 0, +7, +14 and after engraftment in 20 patients with acute GVHD and 40 matched control patients with PTCy-based prophylaxis. Low levels of IL-8 (p=0.04) on day +7 and IFN-γ (p=0.03) after engraftment were associated with grade II-IV acute GVHD. The same pattern was observed for severe acute GVHD. Low IFN-γ after engraftment was also associated with increased non-relapse mortality (p=0.014). No impact of cytokine levels on overall survival and relapse incidence was observed (p>0.05). In conclusion, the dynamics of IL-8 and IFN-γ in GVHD patients after PTCy was different from previously reported after conventional prophylaxis.

[Adult B-cell acute lymphoblastic leukemias: Conclusions of the Russian prospective multicenter study ALL-2009]. / Ostrye V-limfoblastnye leikozy vzroslykh: vyvody iz Rossiiskogo prospektivnogo mnogotsentrovogo issledovaniia OLL-2009.

AIM: To analyze the efficiency and reproducibility of the ALL-2009 protocol within the Russian prospective multicenter study based on different principles of cytostatic effects (non-intensive, but continuous cytotoxic treatment and a small number of allogeneic hematopoietic stem cells). SUBJECTS AND METHODS: The ALL-2009 (NCT01193933) study conducted in April 2009 to December 2016 included 194 patients (95 males and 99 females) aged 15 to 55 years (median age 28 years) with Ph-negative B-cell acute lymphoblastic leukemia (ALL). There was early pre-B-cell ALL in 54 patients, common ALL in 101, pre-B ALL in 39, initial leukocytosis in 9.4·109/l (0.4-899.0), lactate dehydrogenase in 901 IU (31-13 059), an initial central nervous system lesion in 17 (8.7%), mediastinal injury in 3 (1.5%), and splenomegaly in 111 (57.2%). The results of standard cytogenetic analysis are known in 113 (60.4%) patients. Normal karyotypes were detected in 49 (54.5%) out of the patients; t(4;11) in 9 (5.4%), t(1;19) in 2 (1.2%), and other karyotypic abnormalities in 53 (46.9%). Thirteen (7.8%) patients underwent allogeneic hematopoietic stem cell transplantation in first complete remission (CR); their proportion did not differ in the federal and regional centers. RESULTS: The frequency of CR achievement was the same in the federal and regional centers and generally amounted to 87.5%. Early (8.8%) and CR (9.6%) mortality rates remained high despite the low aggressiveness of cytotoxic action, necessitating the improvement of auxiliary treatment. The five-year overall survival (OS) rates vary considerably in the federal and regional centers (72.6 and 43.8%), the relapse-free survival (RFS) (70.2 and 53.4%) and recurrence risk (23.1 and 36.5%) are comparable. This suggests that the non-intensive, but continuous exposure principle built in the ALL-2009 protocol makes it possible to reproduce the envisaged treatment program and to achieve satisfactory results. CONCLUSION: The ALL-2009 protocol allows both the federal and regional centers to obtain the long-term results comparable with those of current foreign studies: OS (54.2%), RFS (56.5%); and relapse risk (35.4%). Multivariate analysis has identified age (over 30 years), initial leukocytosis (30·109/l and more) and t(4;11) among the main clinical prognostic factors. Gene mutation detection evaluated in a small number of patients (8/36) is not a poor prognostic sign. There is a need for further investigations with centralized evaluation of the mutation status of leukemic cells and the clearance of minimal residual disease.

[Acute Ph-negative lymphoblastic leukemias in adults: Risk factors in the use of the ALL-2009 protocol]. / Ostrye Ph-negativnye limfoblastnye leikozy vzroslykh: faktory riska pri ispol'zovanii protokola OLL-2009.

AIM: 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. SUBJECTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

SPATIAL ORGANIZATION OF CHROMOSOMES IN MALARIA MOSQUITOES.

Malaria mosquitoes are vectors of dangerous human diseases and a model system for investigations of chromosome evolution, heterochromatin organization, and nuclei architecture in the cells of the reproductive system. Investigations of nurse cells chromosomes are aimed at understanding of mechanisms that cause interspecies differences in the nuclear spatial organization in these cells. One of the most important tasks of this research is the undestanding of molecular organization of the chromosome regions that are attached to the nuclear envelope. In the present review, the recent achievements in this field of research are described and unsolved problems of the spatial chromosome organization are identified.

[Autologous hematopoietic stem cell transplantation as late high-dose consolidation in adult patients with T-cell lymphoblastic leukemias: Results of a Russian multicenter study].

AIM: To analyze the efficiency of the ALL-2009 protocol (ClinicalTrials.gov NCT01 193933) in patients with T-cell leukemias, particularly the role of autologous hematopoietic stem cell transplantation (auto-HSCT) after non-myeloablative BEAM conditioning, followed by maintenance therapy. SUBJECTS AND METHODS: Since 2009, the ALL-2009 study has enrolled 90 patients with T-cell acute lymphoblastic leukemia (T-ALL), the treatment results were assessed in 86 patients: 6 and 28 patients underwent allogeneic HSCT and auto-HSCT, respectively. A landmark analysis was used to compare survival rates in patients who had undergone auto-HSCT and in those who had not. For this, the median time from complete remission to the date of auto-HSCT was determined (the median was 6 months). Then to compare with the auto-HSCT group, only 27 patients who had been in complete remission for 6 months or more were included in a chemotherapy group. RESULTS: The achievement of complete remission in patients with thymic T-ALL (100%) was significantly higher than in those with early (85.7%) or mature (70%) variants. The patients with early and mature T-ALL as compared to those with thymic T-ALL showed high death rates in the remission induction (7.4 and 10% versus 0) and the patients with mature T-ALL had a.higher proportion of refractory forms (20% versus 0). The 5-year overall and relapse-free survival rates in all the T-ALL patients were 66 and 76%, respectively. After auto-HSCT, the risk of recurrence was 0% versus 21% after chemotherapy (p=0.03). The relapse-free survival rates significantly differed in the auto-HSCT and non-auto-HSCT groups: 100 and 66%, respectively (p=0.047). CONCLUSION: The long-term survival rates obtained during this multicenter study in the T-ALL patients treated according to the ALL-2009 protocol, the basis for which is the principle of continuity of cytostatic effects, are exclusively optimistic. Late consolidation with auto-HSCT following non-myeloablative BEAM conditioning, followed by maintenance therapy, considerably reduces the risk of recurrence.

[Bacterial infections in the early period after allogeneic bone marrow transplantation].

AIM: To study the incidence and risk factors of bacterial infections and the efficiency of empirical antibacterial therapy in patients in the early period after allogeneic hematopoietic stem cell transplantation (allo-HSCT). SUBJECTS AND METHODS: The study included 155 patients who had undergone allo-HSCT. Myeloablative conditioning was used in 39% of the patients. All the patients with neutropenia (NP) received antibiotic prophylaxis with fluoroquinolones until recovery of white blood cell counts or before systemic antibiotic therapy. Antibiotic therapy and a change of antibiotics were considered effective in achieving persistent apyrexia and positive clinical changes. RESULTS: The incidence of febrile neutropenia (FNP) in the patients after allo-HSCT was 63%. The duration of grade 4 leukopenia did not depend on the conditioning regimen. Neutropenic fever was noted in 68% of the patients with NP lasting longer 10 days. In shorter-duration NP, the rate of fever was 52%. Among the patients with mucositis, the frequency of FNP episodes was significantly higher (69% versus 52%; p=0.02). The diverse spectrum of isolated bacteria was represented as gram-positive cocci in 45% of cases; Klebsiella pneumoniae and Enterobacter cloacae were more common among gram-negative ones (24%). The efficiency of empirical antibiotic therapy was 57% (25% for monotherapy, 53% for combined treatment regimens); the early mortality was 2%. CONCLUSION: Infection-related FNP is noted in 68% of the patients in the early posttransplantation period and the risk factors of its development are NP duration, oral colonization with pathogens, and the absence of invasive mycosis after allo-HSCT. Antibacterial prophylaxis significantly decreases the incidence of bacterial complications. Empirical monotherapy with third- or fourth-generation cephalosporins and carbapenems against infections in a transplantation patient is as effective as their combination with aminoglycosides.

Cryogenic distillation facility for isotopic purification of protium and deuterium.

Isotopic purification of the protium and deuterium is an important requirement of many physics experiments. A cryogenic facility for high-efficiency separation of hydrogen isotopes with a cryogenic distillation column as the main element is described. The instrument is portable, so that it can be used at the experimental site. It was designed and built at the Petersburg Nuclear Physics Institute, Gatchina, Russia. Fundamental operating parameters have been measured including a liquid holdup in the column packing, the pressure drops across the column and the purity of the product at different operating modes. A mathematical model describes expected profiles of hydrogen isotope concentration along the distillation column. An analysis of ortho-parahydrogen isomeric composition by gas chromatography was used for evaluation of the column performance during the tuning operations. The protium content during deuterium purification (≤100 ppb) was measured using gas chromatography with accumulation of the protium in the distillation column. A high precision isotopic measurement at the Institute of Particle Physics, ETH-Zurich, Switzerland, provided an upper bound of the deuterium content in protium (≤6 ppb), which exceeds all commercially available products.

[APPLICATION OF PREPARATION OF COCARNIT FOR PATIENTS AFTER ENDOPROSTHESIS OF HIP AND KNEE JOINTS].

In the article the results of clinical researches of efficiency of preparation of Cocarnit are resulted for patients after endoprosthesis of large joints. It is routine that for patients, receiving preparation of Cocarnit after the operation period there was a decline in the amount of complaints of patients on the total somatical state. Preparation of Ccocarnit was positively estimated outside patients, meaningful by-reactions, serving reason of abolition of preparation, was not marked. At the reception preparation of Cocarnit greater part of investigational laboratory indexes (table of contents of glucose, ß-lipoproteines, total chondroitisulfates, TBC-productes (malonic dyaldehyde), activity of aspartataminotransferase, alkaline phosphatase and ß-glutamyltranspeptidase), the indexes of clinical blood test and leucocytar indexes during a supervision did not have reliable differences from such as the persons of the control group, that confirms good bearab leness of the indicated preparation. Application preparation of Cocarnit for patients in composition the chart of treatment of patients after endoprosthesis of large joints brought maintenance over of cholesterol to the decline, glycoproteins, TBC-products (malonic dyaldehyde), activity of alaninaminotransferase, that specifies on normalizing influence of the indicated preparation in relation to the basic types of exchange of matters.

[Russian experts' clinical guidelines for acute myeloid leukemia treatment in patients less than 60 years of age].

The purpose of the paper is to present Russian experts' consolidated opinion about acute myeloid leukemia (AML) treatment in adult patients aged less than 60 years. The guidelines have been elaborated having regard to foreign publications and Russian experience, on the basis of global and Russian clinical trials to treat AML and to define indications for allogeneic bone marrow transplantation in patients during first complete remission.

Morpho-functional characteristics of the scolex of Wardium chaunense (Cestoda: Aploparaksidae) penetrated into host intestine.

The scoleces of Wardium chaunense penetrated into the intestinal wall of a snipe (Gallinago gallinago) were examined by light and transmission electron microscopy for the first time. Naturally, the scolex is characterised by a shorter length in comparison with when it is removed from the host. Ultrastructural characteristics of the main parts of the scolex, such as suckers, rostellum and rostellar sac are reported. Partial degradation of the radial muscles of the suckers is clearly recognised; this can be the result of a deep penetration of the scolex into the mucosa and subsequent loss of attachment function by suckers. The muscular walls of the rostellum and rostellar sac have a structure of the same type: an outer longitudinal layer of muscles is separated from the inner circular one with a thin basal matrix, which, also, surrounds each muscular fibre of the circular layer. Circular fibres consist of mutually perpendicular myofibrils, connected with the basal matrix by hemidesmosomes. Microtriches, covering the tegument, vary in shape in different regions of the scolex. They are absent on the apical part of the rostellum, and are slightly curved and can be considered as belonging to the fixative type on the suckers. Special sensory endings with a dense central body and without cilia are situated at the distal cytoplasm of the tegument of the suckers. Two glands, having the same syncytial structure, are disposed inside the rostellum and rostellar sac. Erythroid granules produced by the glands are released during an apocrine process into the host-parasite contact zone. Secretions of the cestode tegument in the form of vesicles and bubbles of granular material were also observed. It is suggested that the scolex attachment method of W. chaunense has the tendency of 'anchoring', which is an irreversible attachment used by some cestode parasites of the snipe.

[Allogeneic hematopoietic stem cell transplantation for acute myeloblastic leukemia in first remission].

AIM: To evaluate the efficiency of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloblastic leukemia in first remission depending on the regimens of conditioning, the source of a graft, and the characteristics of a donor and a recipient. SUBJECTS AND METHODS: In 66 treated patients, including from partially HLA-mismatched relatives (n=4), the efficiency of allo-HSCT from related donors (n=26) and unrelated donors (n=40), were compared. According to cytogenetic findings, 7 (11%), 31 (47%), and 10 (15%) patients belonged to low-, intermediate-, and high-risk groups, respectively. RESULTS: Five-year overall survival (OS) and mortality associated with transplantation were 56 and 22% for allo-HSCT from related donors, 68 and 23% for that from HLA-matched donors, and 71 and 25% for that from partially HLA-mismatched donors, respectively (p=0.8 and p=0.7). The relapse risk after allo-HSCT from unrelated donors was significantly lower than after that from related donors (13 and 35%, respectively; p=0.8). Univariate analysis showed that the OS rates depended on the cytogenetic risk group (OS was 24 and 64% in the high- and intermediate-risk groups, respectively (p=0.027). The relapse risk in chronic graft-versus-host reaction (GVHR) and in grade 3 acute GVHR (p=0.01) was shown to be less than that in grades 1-2 acute GVHR (p=0.06). CONCLUSION: OS rates after allo-HSCT from related and unrelated donors were comparable and unrelated to the source of a graft, the regimen of conditioning, and other characteristics of a donor and a recipient.

[Efficacy of donor lymphocyte infusion in patients after different types of allogeneic hematopoietic stem cell transplantation].

AIM: To evaluate the efficacy of donor lymphocyte infusion (DLI) to prevent and treat recurrences in patients after different types of allogeneic hematopoietic stem cell transplantation (allo-HSCT). SUBJECTS AND METHODS: Data from 118 patients with malignant blood diseases were analyzed. Allo-HSCTs from HLA-matched related donors (n=49), HLA-matched unrelated donors (n=50), partially HLA-matched unrelated donors (n=2), and haploidentical donors (n=24) were performed. The indications for DLI were underlying disease relapse (59 DLIs), resistant disease course (n=40), minimal residual disease (n=1 6), falling donor chimerism (n=1 5), and recurrence prevention (n=1 3). RESULTS: Therapy response was obtained after 57 (44%) DLls. There were 36 (25%) and 30 (21%) cases of acute and chronic graft-versus-host reactions (GVHR), respectively. The use of DLI from HLA-matched donors, its performance in the periods of D+100 to one year after allo-HSCT, a donor chimerism level of over 90% at the moment of DLI, the administration of the initial DLI dose of below 1.10(6) CD3+/kg, and the development of chronic GVHR after DLI were associated with the highest rate of therapy responses. The overall survival rates of patients with DLI were significantly influenced by factors, such as DLI periods, donor chimerism levels at DLI, and the development of chronic CVHR after DLI. CONCLUSION: The choice of the optimal dose of cells, the periods of DLI and its preventive administration improve prognosis in patients after allo-HSCT. The occurrence of acute GVHR is affected by the degree of HLA matching and the type of a donor. The development of chronic GVHR after DLI is associated with the highest rate of responses to DLI and higher survival rates.

[Efficiency of treatment of adult patients with acute T-lymphoblastic leukemia according to the ALL-2009 protocol of the Russian Acute Leukemia Study Group].

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.

[Extracorporeal photopheresis in the treatment of patients with refractory chronic graft-versus-host disease after allogeneic bone marrow transplantation].

AIM: To evaluate the efficiency of extracorporeal photopheresis (ECP) in the treatment of patients with refractory chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). SUBJECTS AND METHODS: The study included 49 patients aged 2 to 55 years. Allo-HSCT was carried out in 38 (79%) patients with acute leukemias, 5 (10%) with chronic leukemias, 4 (8%) with myelodysplastic syndrome/myeloproliferative disease, and 2 (3%) with other hematologic diseases. The patients included in the study had glucocorticosteroid (GCS)-refractory disseminated cGVHD or a history of severe complications from GCS therapy. RESULTS: When evaluating the efficiency of therapy, its response was recorded in 37 (77%) cases; the best results were obtained in patients with hepatic (82%), mucosal (76%), and skin (74%) lesions. The mean severity according to the cGVHD Working Group, National Institutes of Health, and a platelet level of more than 100.10(9)/1 were defined as factors improving a therapy response. In the patients receiving ECP, the overall survival was 70%. The latter was higher in the group of patients who had responded to ECP therapy without involving the gastrointestinal tract in the cGVHD process and in those receiving a combination of ECP and other immunosuppressive drugs. CONCLUSION: ECP is an effective treatment for patients with refractory cGVHD, it may be used in those with a history of severe complications from GCS therapy. ECP allows the dose of GCS to be reduced to the point of complete discontinuation.