V(D)J Recombination Excision Circles of B- and T-cells as Prognostic Marker in B-Cell Chronic Lymphocytic Leukemia

Background & Aims. T-cell receptor excision circles (TREC) and κ-deleting recombination excision circles (KREC) are extrachromosomal DNA segments generated during V(D)J re combination process that characterize the diversity of the antigen repertoire of T- and B-cells. The aim of our study is to identify the prognostic value of the excision circles in the chronic lymphocytic leukemia (CLL) setting. Methods. The excision circles’ levels were assessed by means of real time PCR in 109 patients with high-risk CLL and 16 matched healthy individuals. Results. KREC levels were signifi cantly (p < 0.001) lower in CLL patients vs. the reference group. TREC levels were lower in groups with unmutated status of immunoglobulin heavy chain variable region genes (p < 0.05) and 11q deletions (p < 0.1). Moreover, the KREC levels were higher in NOTCH1 mutation carriers than in noncarriers (p < 0.05). The comparison of treatment outcomes demonstrated a correlation between a high TREC level and achievement of complete remission. The prognostic value of the biomarker was confirmed by ROC-analysis: AUCTREC = 0.713 (p = 0.001) Conclusion. Association between excision circles’ levels and clinical/laboratory CLL prognostic factors, as well as complete remission achievement, makes possible the implementation of the test for early prediction of the treatment outcome

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Epstein-Barr Virus in Patients with Classical Hodgkin’s Lymphoma

Background. A close relationship between Epstein-Barr virus (EBV) and classical Hodgkin’s lymphoma (cHL) has been established in approximately 1/3 patients. EBV-positive lymphomas are characterized by increased level of EBV specific antibodies emerging long before tumor symptoms, аs well as a high plasma EBV DNA concentration. These viral markers normally correlate with clinical manifestations and the outcome of treatment performed. In patients with EBV-negative lymphomas, however, there has been no attempt to assess the clinical significance of either humoral response to EBV or EBV DNA concentration in plasma. Aim. To evaluate diagnostic and prognostic significance of EBV markers in patients with EBV-negative lymphomas. Methods. The clinical trial included 13 cHL-patients admitted at the Department of chemotherapy of hemoblastoses of NN Blokhin National Medical Cancer Research Center. The male to female ratio was 1:1.3, the median age was 26.4 years. Leukocyte and lymphocyte counts were evaluated in all the patients before, during, and after treatment as well as throughout the follow-up period. The same indicators were analysed in the control group which contained 40 healthy persons (with the median age of 41.1 years, male to female ratio 1.5:1). The study was based on serologic test for EBV antibodies and quantitative analysis of the viral DNA copy number in plasma. Results. The obtained data show a low immunie response to EBV and its diminishment after several polychemotherapy treatment cycles, correlating with decreased leukocyte and lymphocyte levels. As opposed to levels of virus-specific antibodies which do not reflect the efficacy of anticancer therapy, plasma EBV DNA concentration in 2 patients decreased to 0 after remission had been achieved. Conclusion. Although the number of observations is limited, one could suggest that viral load values in plasma of patients with EBV-negative lymphomas can prove to be a useful marker of anticancer therapeutic effect. Additional studies of these markers are required

Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Russian Multicenter Clinical Trial

Background. Recent advances in the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R ALL) are attributed to the implementation of immunotherapy methods which include blinatumomab, the bispecific engager of a patient’s endogenous T-cells (Blincyto™, Amgen®) (BC). Aim. To assess BC efficacy and toxicity in the treatment of R/R ALL patients with persistence of minimal tumor clone before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Materials & Methods. The trial included 66 B-ALL patients with CD19+ aged 18 to 72 years, 23 (35 %) of them with measurable minimal residual disease (MRD+) and 43 (65 %) with R/R ALL. In 18 (27 %) patients BC was administered after prior allo-HSCT. Results. In the overall group 2-year overall survival (OS) and disease-free survival (DFS) in patients with response to BC treatment were 53 % and 38 % respectively. In the R/R ALL group complete remission (CR) was achieved in 29 (67 %) patients including 24 (83 %) patients with negative MRD. CR rate was higher in standard cytogenetic risk group (73 %) in comparison with high-risk group (59 %). In patients with more or less than 50 % blast cells in bone marrow CR rate was 85 % and 61 %, respectively. When BC was administered after prior allo-HSCT and without it CR rate was 80 % and 60 %, respectively. In R/R ALL patients with response to BC 2-year OS and DFS were 40 % and 26 %, respectively, in the MRD+ group of ALL patients they were 66 % and 51 %, respectively. Relapse rate was lower in the group with allo-HSCT than in the group without it, i.e. 21 % vs. 55 %. Adverse events of grade 3–4 were observed in 25 (38 %) patients. In 11 (16 %) patients BC therapy had to be discontinued, in 5 (7 %) patients it was terminated prior to the scheduled date. Conclusion. BC efficacy is higher in the MRD+ group and in R/R ALL patients with smaller tumor mass. BC treatment after allo-HSCT yields remissions in most patients and can be combined with immune-adoptive therapy

Search for excited electrons singly produced in proton–proton collisions at \sqrt{s} = 13 TeV with the ALAS experiment at the LHC

A search for excited electrons produced in pp collisions at s√ = 13 TeV via a contact interaction qq¯→ee∗ is presented. The search uses 36.1 fb −1 of data collected in 2015 and 2016 by the ATLAS experiment at the Large Hadron Collider. Decays of the excited electron into an electron and a pair of quarks ( eqq¯ ) are targeted in final states with two electrons and two hadronic jets, and decays via a gauge interaction into a neutrino and a W boson ( νW ) are probed in final states with an electron, missing transverse momentum, and a large-radius jet consistent with a hadronically decaying W boson. No significant excess is observed over the expected backgrounds. Upper limits are calculated for the pp→ee∗→eeqq¯ and pp→ee∗→eνW production cross sections as a function of the excited electron mass me∗ at 95% confidence level. The limits are translated into lower bounds on the compositeness scale parameter Λ of the model as a function of me∗ . For me∗<0.5 TeV , the lower bound for Λ is 11 TeV . In the special case of me∗=Λ , the values of me∗<4.8 TeV are excluded. The presented limits on Λ are more stringent than those obtained in previous searches

Measurements of Higgs bosons decaying to bottom quarks from vector boson fusion production with the ATLAS experiment at √=13TeV

The paper presents a measurement of the Standard Model Higgs Boson decaying to b-quark pairs in the vector boson fusion (VBF) production mode. A sample corresponding to 126 fb−1 of s√=13TeV proton–proton collision data, collected with the ATLAS experiment at the Large Hadron Collider, is analyzed utilizing an adversarial neural network for event classification. The signal strength, defined as the ratio of the measured signal yield to that predicted by the Standard Model for VBF Higgs production, is measured to be 0.95+0.38−0.36 , corresponding to an observed (expected) significance of 2.6 (2.8) standard deviations from the background only hypothesis. The results are additionally combined with an analysis of Higgs bosons decaying to b-quarks, produced via VBF in association with a photon

The ATLAS inner detector trigger performance in pp collisions at 13 TeV during LHC Run 2

The design and performance of the inner detector trigger for the high level trigger of the ATLAS experiment at the Large Hadron Collider during the 2016-2018 data taking period is discussed. In 2016, 2017, and 2018 the ATLAS detector recorded 35.6 fb(-1), 46.9 fb(-1), and 60.6 fb(-1) respectively of proton-proton collision data at a centre-of-mass energy of 13TeV. In order to deal with the very high interaction multiplicities per bunch crossing expected with the 13TeV collisions the inner detector trigger was redesigned during the long shutdown of the Large Hadron Collider from 2013 until 2015. An overview of these developments is provided and the performance of the tracking in the trigger for the muon, electron, tau and b-jet signatures is discussed. The high performance of the inner detector trigger with these extreme interaction multiplicities demonstrates how the inner detector tracking continues to lie at the heart of the trigger performance and is essential in enabling the ATLAS physics programme