Studying a collection of common-wheat varieties for leaf rust resistance, crop yield and grain quality in the environmental conditions of Novosibirsk region.

The relationship between a variety's genotype, environmental conditions and phytopathogenic load are the key factors contributing to high yields that should be taken into account in selecting donors for resistance and high manifestation of valuable traits. The study of leaf rust resistance in 49 common wheat varieties was carried out in the field against the natural pathogen background and under laboratory conditions using single-pustule isolates with virulence to Lr9 and Lr24. It has been shown that the varieties carrying alien genes Lr6Agi2 (Tulaikovskaya 10) and Lr6Agi1 (Voevoda) were resistant to leaf rust infection both in the field and in the laboratory. Varieties KWS Buran, KWS Akvilon, KW 240-3-13, and Etyud producing crop yields from 417 to 514 g/m2 comparable to the best standard variety Sibirskaya 17 can be reasonably used as Lr24 resistance gene donors under West Siberian conditions. Omskaya 44 variety showing crop yield of 440g/m2 can be used as a donor for Lr19 and partially effective Lr26. Varieties Tuleevskaya and Altayskaya 110 with Lr9 in their genomes are recommended for the development of resistance gene-pyramided genotypes. The highest protein and gluten contents were observed in the CS2A/2M sample, while KWS Buran, Altayskaya 110, Volgouralskaya, and KWS Akvilon showed the lowest values. Varieties CS2A/2M, Tulaikovskaya 10, Pavon, and Tuleevskaya were ranked the highest in micro- (Cu, Mn, Zn, Fe) and macronutrient (Ca, Mg, K) contents among the common wheat samples from the collection, while the lowest values for most elements were observed in KWS Buran, Novosibirskaya 15, and Volgouralskaya. Winter varieties demonstrating leaf rust resistance against the infectious background typically carry adult plant resistance genes (Lr34, Lr12, and Lr13), particularly combined with the juvenile Lr26 gene. The presence of Lr41 in a winter type line (KS 93 U 62) allowed it to maintain resistance against a leaf rust pathogen clone kLr24, despite the presence of Lr24 in the genotype. Varieties Doka and Cheshskaya 17 may act as donors of resistance genes Lr26 + Lr34 and Lr9 + Lr12 + Lr13 + Lr34, as well as sources of dwarfing without losses in winter hardiness and yield under West Siberian conditions.

Tandem autologous hematopoietic stem cell transplantation for embryonal brain tumors in infants and very young children.

Withdrawal of radiotherapy in patients with brain tumors under four years decreases chance for cure. AutoHSCT in a series of pilot studies demonstrated a potential to improve outcomes in these patients. The study included 50 patients with median age of 39 months (7-53). Medulloblastoma (n = 28, 56%), ETMR (n = 9, 18%) and other histological types (n = 13, 26%) were most commonly diagnosed. Forty two patients (84%) received tandem autoHSCT by HIT-MED protocol, and single autoHSCT was performed in eight children (16%). Adjuvant radiotherapy was administered in 25 (50%) children and treatment of relapse included radiotherapy in 6 (12%). Median follow-up was 39.6 months (6-121). Long-term CIR was 37%, and TRM - 6%. Five-year OS was 71% in medulloblastoma, 37% in ETMR and in other tumors - 51% (p = 0.07). Irradiation-free OS at 5 years for children with medulloblastoma was 24%. For the whole cohort of CNS tumors, independently of histology, OS and PFS at five years were 60% and 46%, respectively Young children with medulloblastoma, following tandem autoHSCT, demonstrate OS comparable to older children. Patients with other histological types demonstrate suboptimal long-term survival rates after autoHSCT and one should assess whether these patients benefit from autoHSCT.

[FEATURES OF THE MANIFESTATION OF REHABILITATIVE ACTIVITY IN PATIENTS WITH PRINCIPAL DISABLING PATHOLOGIES].

The article presents the results of a psychological study of patients with principal disabling pathologies that form the main structure of disability in the Russian Federation due to malignant neoplasms: diseases of the circulatory system; diseases of the musculoskeletal system and connective tissue; diseases of the endocrine system and metabolic disorders (diabetes mellitus of the first and second types). The article presents the results of studying a sample of patients by various psychological parameters, provides statistical comparisons of psychological characteristics of patients depending on the specifics of their social situation, in which patients either claim to be disabled and are under conditions of medical and social expertise, implying the possibility of changing social status, or patients of the same nosological categories, who do not claim to be disabled and who are rehabilitating on the basis of their own personal and socio-environmental resources outside of the "disabled" status. Psychological techniques are presented, the specificity of emotional and personal parameters is analyzed and characterized, including personality frustration and experience of the significance of the disease in the spheres of life, self-esteem indicators, identification characteristics, strategies that provide rehabilitation adherence, which characterize the activity of patients in the compared groups in many ways. The conceptual position that defines the activity of patients as «rehabilitative¼ has been substantiated. The results of the study revealed statistically significant differences in psychological indicators in the compared groups of patients rehabilitating outside the "disabled" status and patients claiming to be disabled. The indicators obtained in the study indicate that the personal self-regulation of patients rehabilitating outside the «disabled¼ status qualitatively differs from the self-regulation of patients claiming disability, in terms of stable self-esteem and belief in the ability to realize life in significant areas of social functioning, in the ability of perspective planning of the future, in active self-realization of social roles, active participation in interpersonal, leisure, professional, household and other spheres, high responsibility for one's health, against the background of stable emotional perception of the current social situation of the disease.

Long-term outcomes of ruxolitinib therapy in steroid-refractory graft-versus-host disease in children and adults.

Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III-IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57-89%) in acute GVHD and 81% (95% CI 67-92%) in chronic. Overall survival was 59% (95% CI 49-74%) in acute group and 85% (95% CI 70-93%). The major risk factors for lower survival were grade III-IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III-IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.

Efficacy of Dasatinib in a CML Patient in Blast Crisis with F317L Mutation: A Case Report and Literature Review.

The introduction of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has significantly increased survival rate and quality of life for patients with CML. Despite the high efficacy of imatinib, not all patients benefit from this treatment. Resistance to imatinib can develop from a number of mechanisms. One of the main reasons for treatment failure is a mutation in the BCR-ABL gene, which leads to therapy resistance and clonal evolution. Clearly, new treatment approaches are required for patients who are resistant to imatinib. However, mutated clones are usually susceptible to second-generation TKIs, such as nilotinib and dasatinib. The choice of the therapy depends on the type of mutation. A large trial program showed that dasatinib is effective in patients previously exposed to imatinib. However, for a minority of patients who experience treatment failure with TKI or progress to advanced-phase disease, allogeneic stem cell transplantation (allo-SCT) remains the therapeutic option. In spite of the high curative potential of allo-SCT, its high relapse rate still requires a feasible strategy of posttransplant treatment and prophylaxis. We report a case of a CML patient with primary resistance to first-line TKI therapy. The patient developed an undifferentiated blast crisis. Before dasatinib therapy, the patient was found to have an F317L mutation. He was successfully treated with dasatinib followed by allo-SCT. In the posttransplant period, preemptive dasatinib treatment was used to prevent disease relapse.

[Effectiveness of high-dose polychemotherapy with autologous hemopoietic stem cell transplantation in the treatment for malignant tumors of the central nervous system in children and young adults].

A total of 40 patients (median age 6 years, range 1-28 years) with high-risk malignant brain tumors received a single (n = 35) or tandem (n = 5) high-dose chemotherapy (HDCT) with autologous hemopoietic stem cell transplantation (auto-HSCT). The 2-year OS and DFS are 52% and 47%, accordingly, with median follow-up of 24 (range 2-96) months. The patients without complete response at the time of auto-HSCT had worst prognosis with 53% DFS in patients with partial remission and 25% in patients with disease stabilization (p = 0.001). Patients with relapsed tumor had worse prognosis, than high-risk patients in the first remission with DFS 26% and 62%, accordingly (p=0.02). The relapse rate also correlated with patient's age (38% DFS in patients younger, than 4 years and 60% in older patients, p = 0.005) and tumor morphology (63% DFS in patients with medulloblastoma, 60% in patients with germ-cell tumors, 45% in other embryonal CNS tumors, p = 0.05). The 4th-grade transplant-related toxicity and mortality rates were observed in 13% and 18% of patients, accordingly. Therefore, HDCT with auto-HSCT in young patients with high-risk CNS tumors is characterized by acceptable toxicity and allows improving overall therapy results.

[Combined therapy for children and adolescents with Ewing tumors (a 25-year experience)].

A total of 115 children (median age 10.5 years, range 2-17) with Ewing sarcoma family tumors (ESFT) received therapy in N.N. Petrov Institute of Oncology pediatric department from April 1985 till August 2013. These patients were divided into two groups depending on treatment tactics used: patients treated according to modified T9 protocol (n = 64) and patients treated according to EICESS-92 or Euro-Ewing 99 regimens (n = 51). Twenty four patients from the second group with adverse prognostic factors received high-dose chemotherapy with autologous stem cell transplantation. All patients received surgical treatment and/or irradiation for primary tumor local control. Five-year overall and disease-free survival was 39% and 37,9% in the first group. In the second group these values were significantly higher; 55% and 39.5%, accordingly (p = 0.03 and 0.25). All patients from the first group with primary metastatic ESFT died of disease progression, while in the second group OS and DFS reached 45.8% and 28.9%, accordingly. There was a statistically significant correlation between local relapse rate and irradiation dose biological equivalent (in TDF units). The local relapse cumulative rate was minimal (12,6%) in patients receiving 80 TDF.

[Evaluation of ovarian status in women who received anti-tumor therapy in childhood and adolescence].

The paper presents the results of a study of the ovarian reserve in young women who received treatment for malignant tumors in childhood and adolescence and are in complete clinical remission. The function of the reproductive system was evaluated by serum concentrations of gonadotropins, estradiol, anti-Müllerian hormone (AMH) and inhibin B. The results were compared to the treatment, patients' age at the beginning of therapy and at the time of the examination. AMH level in serum was the most informative indicator of ovarian reserve in patients treated for malignant tumors.

[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.

[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.

[Complex chromosome damages in patients with recurrent acute leukemias after allogeneic hematopoietic stem cell transplantations].

AIM: To study the pattern of complex chromosome damages (CCD) in acute leukemias (AL) and their place in the development of post-transplant recurrences (PTR) of AL. MATERIALS AND METHODS: Cytogenetic and partially molecular biological studies of bone marrow cells were conducted in 10 patients with PTR. Of them, 6 patients were diagnosed as having acute lymphoblastic leukemia (ALL), including T-ALL and Ph-positive ALL in 2 and 4 patients, respectively; and 4 patients had acute non-lymphoblastic leukemia (ANLL), including one case secondarily induced by previous polychemotherapy (PCT) and irradiation. The standard G-band staining technique complemented by multicolor fluorescence in situ hybridization in one of the cases was used. RESULTS: It was shown that CCD had the similar pattern in 4 patients before transplantation and in PTR, progressed in 4 more patients, was absent or unnoticed in the early stage of the disease. The other recurrent chromosomal abnormalities that are worthy of notice are as follows: a) the presence of two Ph chromosomes in the cells of two of the 4 patients with Ph+ ALL; b) the frequent involvement of chromosome pairs 9, 19, 5, and 7 into the numerical and structural rearrangements. CONCLUSION: The important feature of PTR of AL is cellular CCDs, a portion of which is clearly related to previous PCT and may be of pathogenetic value for the development of recurrences.

[The experience in non-relative allogenic transplantation of stem hemopoietic cells in the Clinic of Bone Marrow Transplantation at I.P. Pavlov St-Petersburg Medical Academy].

AIM: To evaluate efficacy of allogenic transplantation of hemopoietic stem cells (allo-THSC) from non-relative donor in patients with hematological diseases in the Clinic of Bone Marrow Transplantation at L.P. Pavlov St-Petersburg Medical Academy for the period 2000-2006. MATERIAL AND METHODS: A total of 84 allo-THSC from non-relative donor to patients aged from 10 months to 65 years (median 18 months, 44 years) was carried out. RESULTS: Six-year overall survival (OS) in all the patients was 51.4%, in remission of AML--66.7%, ALL--33%, depending on the presence or absence of acute reaction graft versus host reaction (GVHR)--54 and 50.9%, chronic FVHR--75.6 and 58.2%, blood group compatibility or incompatibility in donor/recipient pairs--58.4 and 47.9%, by gender--61.4 and 40.6%, in use of HSC of the bone marrow--58.3%, peripheral blood--26.7%. OS in the dose of transplanted CD 34+ cells per 1 kg body mass < 5.0 x 10(6)/kg--173%, in the dose 5.0--8.0 x 10(6)/kg--38.8%, > 8.0 x 10(6)/kg--35.5%. Acute GVHR developed in 56% patients, chronic--in 20%, hemorrhagic cystitis--in 27.7%, bacterial, cytomegalovirus and fungal infection--in 10, 70 and 30%, respectively. The causes of death were acute GVHR (20%), infection 99%), polyorganic failure (4%), transplant rejection (5.3%), recurrence (18.7%). CONCLUSION: Bone marrow transplantation clinics in the Russian Federation must develop all kinds of allo-THSC--relative, non-relative and haploidentical using bone marrow, peripheral blood, umbilical blood as the source of HSC. It is necessary to create a national register of non-relative donors.

[Lymphoid tissue in the tracheal wall of stress-sensitive wistar rats after exposure to stress].

Using the histological and histochemical methods, the changes of cell composition in mucosal lamina propria and submucosa of the tracheal wall were studied in 20 Wistar male rats, predisposed to stress. 10 rats formed the control group, while other 10 (experimental group) were subjected to immobilization with electrocutaneous irritation (emotional stress). It was demonstrated that after exposure of animals to emotional stress, the number of large lymphocytes per unit area of the section was increased in the basis and the cupola of lymphoid nodules, while the number of small lymphocytes in the basis of lymphoid nodules was decreased. The number of cells with the signs of destruction per unit area of the section was increased as compared to that in control group. The number of small lymphocytes around the excretory ducts of the glands was increased almost 1.5 times after the exposure to stress.

[T-cell panniculitis-like lymphoma of the subcutaneous fat: clinicomorphological and immunohistochemical analysis].

3 cases of T-cell panniculitis-like lymphoma of the subcutaneous fat are reported. Clinical, histological and immunohistochemical findings are presented. Histologically, we found lobular structure, atypical small and middle-size lymphoid cells, angiocentric growth, erythrophagocytosis. Immunohistochemically it was a cytotoxic phenotype of atypical T-cells. T-cell panniculitis-like lymphoma is a special variant of non-Hodgkin's lymphoma which is diagnosed immunohistochemically.

[Polymorphism of the ND1 and CO1 mitochondrial genes in populations of liver fluke Fasciola hepatica]. / Polimorfizm mitokhondrial'nykh genov ND1 i SD1 v populiatsiiakh pechenochnogo sosal'shchika Fasciola hepatica.

Polymorphism of fragments of the ND1 and CO1 mitochondrial genes was for the first time found in four liver fluke Fasciola hepatica samples from Ukraine, Belarus, Moscow region, and Mordovia. The ND1 and CO1 fragments were respectively 292 and 433 bp in size, with polymorphic sites accounting for 2.7 and 0.9% of the total sequence. Seven haplotypes were found in the four samples; two haplotypes (A and B) were most common (29.1 and 45.8%, respectively) in the pooled sample. The haplotype frequency distribution differed among the four populations. Haplotype B prevailed in the Mordovian and Moscow region samples. In addition, these samples had a higher number of unique haplotypes (A2, A3, B2). The results testify to genetic divergence of the four geographically distant populations of F. hepatica.

[Experience in the use of regional methods of anesthesia in oncological and gynecological surgeries]. / Opyt primeneniia regionarnykh metodov anestezii pri oncoginekologicheskikh operatsiiakh.

The block loco-regional methods of anesthesia as applied to onco-gynecology surgery were used in 1310 patients with the predominant 2nd stage ASA risk. The best results (efficiency, safety, convenience) were ensured with spinal anesthesia by intraoperative sedative analgesia (micro-units of midazolam, propofol and ketamine) and by a 0.3 mg single-unit intramuscular injection of buprenorphine (made at the final surgery stage) that prevented a severe postoperative pain syndrome, which was later arrested by an "on-demand" intramuscular injection of peri pheral-action analgetics (ketoprofen or methamezol--therapeutic dose).

[RAPD variation in two trematode species (Fasciola hepatica and Dicrocoelium dendriticum) from a single cattle population]. / RAPD-izmenchivost' dvukh vidov trematod (Fasciola hepatica i Dicrocoelium dendriticum) iz populiatsii krupnogo rogatogo skota.

The method of random DNA amplification by PCR with arbitrary primers (RAPD-PCR) was used for the description and estimation of genetic variation in two trematode species, Fasciola hepatica (n = 21) and Dicrocoelium dendriticum (n = 8). The studied trematodes were liver parasites of five cattle individuals belonging to the same herd. To study the F. hepatica population, five primers were selected, which revealed 320 RAPD markers in five samples of parasites isolated from five different host individuals. Using 87 RAPD markers, a comparison of variation was conducted between F. hepatica and D. dendriticum samples from the same host individual. Based on the estimates of RAPD variation for the individual samples of parasites collected from each of five host individuals and for the total F. hepatica population, standard indices of genetic similarity (S), diversity (H), polymorphism (P), and population subdivision (FST) were calculated. From the indices of similarity in pairs (S), dendrograms were constructed, which reflect genetic relationship between the representatives of two species and between F. hepatica individuals isolated from the same or different host individuals. It was revealed that polymorphism level (P) varied within a range of 35.5 to 83.2% in the studied F. hepatica population and reached 95.1% in the studied D. dendriticum population. Two different trematode species that simultaneously parasitize the same host animal were characterized by similar estimates of polymorphism and genetic diversity and by similar topology of genetic similarity dendrograms. The degree of genetic similarity between F. hepatica and D. dendriticum was significantly lower (20%) than between five F. hepatica samples (41.4%) that formed two unequal clusters. Each of these clusters represents a heterogeneous group consisting of parasites collected from three or four host individuals. In the individual samples of parasites related to each of the studied host individuals, the indices of genetic similarity (S) and diversity (H) varied within a range of 43.3 to 64.8% and 25.1 to 56.6%, respectively. In the total F. hepatica sample, the estimates of intraspecific variation, the topology of dendrograms, and the FST index (7.4%) indicate the absence of clear genetic differentiation between the samples of parasites isolated from different host individuals. Possible reasons for the high level of genetic variation in the studied trematode populations and the genetic consequences of host--parasite interaction are discussed.