Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia

Background & Aims. This paper presents the results of the observational study of ibrutinib in patients with chronic lymphocytic leukemia (CLL), conducted in SP Botkin Municipal Clinical Hospital. The main objective was the analysis of complications of ibrutinib and identification of factors, influencing the dosage regimen; the secondary objective was the estimation of the total response to treatment, event-free and overall survival. Materials & Methods. The study included 96 patients with CLL with indications for ibrutinib therapy. The median age was 64,9 years (range 32–91 years), the study population consisted of 69 (72 %) men and 27 (28 %) women. The condition of 25 (26 %) patients according to the ECOG scale was of > 3 points. The disease of stage C were diagnosed in 36 (37 %) patients . Deletion of 17p/TP53 mutations were detected in 29 (33 %) of 87 patients. Seventy patients had refractory CLL. The median of the number of the lines of the previous therapy was 3 (range 1–9). Adverse events were assessed in accordance with the CTCAE criteria, version 4.0; the bleeding severity was evaluated using ITP-specific bleeding score; hematological complications were classified according to the recommendations of IWCLL-2008. Results. Ibrutinib was administered at a dosage of 420 mg per day daily until progression or intolerable toxicity. The median duration of ibrutinib therapy was 10.3 months. Ibrutinib was shown to have moderate toxicity, mostly of grade I or II. The bleeding was the most frequent complication. Of the hematological complications, thrombocytopenia was the most common (35 %); neutropenia grade III) developed in 26 % of patients. The treatment response was assessed in 92 patients. The overall response to treatment was 89 %. Complete remission, partial remission and partial remission with lymphocytosis were achieved in 4 (4 %), 57 (62 %), and 21 (23 %) patients, respectively. The event-free survival and overall survival by the month 10 was 90 % and 91 %, respectively. For this observation period, ECOG status and the number of the lines of therapy prior to ibrutinib had the prognostic value. Conclusion. Ibrutinib was shown to have high efficiency in relapsed/refractory forms of CLL. The nature of the ibrutinib toxicity is fundamentally different from that of the conventional chemotherapy. The frequency of ibrutinib therapy complications and patients’ non-compliance depends on the intensity of the previous treatment of CLL. Despite a short observation period, it can be concluded that ibrutinib had the greatest impact on the patient’s quality of life when administered for the first relapse. The low toxicity of ibrutinib is likely to allow the combination with other antitumor agents

Overview of the FTU results

Spontaneous increases in plasma density, up to similar to 1.6 times the Greenwald value, are observed in FTU with lithized walls. These plasmas are characterized by profile peaking up to the highest obtained densities. The transport analysis of these discharges shows a 20% enhancement of the energy confinement time, with respect to the ITER97 L-mode scaling, correlated with a threshold in the peaking factor. It has been found that 0.4 MW of ECRH power, coupled at q = 2 surface, are sufficient to avoid disruptions in 0.5 MA discharges. Direct heating of magnetic islands produced by MHD modes determines current quench delay or avoidance. Supra-thermal electrons generated by 0.5 MW of lower hybrid power are sufficient to trigger precursors of the electron-fishbone instability. Evidence of spatial redistribution of fast electrons, on the similar to 100 mu s typical mode timescale, is shown by the fast electrons bremsstrahlung diagnostic. From the presence of new magnetic island induced accumulation points in the continuous spectrum of the shear Alfven wave spectrum, the existence of new magnetic island induced Alfven eigenmodes (MiAE) is suggested. Due to the frequency dependence on the magnetic island size, the feasibility of utilizing MiAE continuum effects as a novel magnetic island diagnostic is also discussed. Langmuir probes have been used on FTU to identify hypervelocity (10 km s(-1)), micrometre size, dust grains. The Thomson scattering diagnostic was also used to characterize the dust grains, present in the FTU vacuum chamber, following a disruption. Analysis of the broad emitted light spectrum was carried out and a model taking into account the particle vaporization is compared with the data. A new oblique ECE diagnostic has been installed and the first results, both in the presence of lower hybrid or electron cyclotron waves, are being compared with code predictions. A time-of-flight refractometer at 60 GHz, which could be a good candidate for the ITER density feedback control system, has also been tested

Alternative splicing: a pivotal step between eukaryotic transcription and translation

Alternative splicing was discovered simultaneously with splicing over three decades ago. Since then, an enormous body of evidence has demonstrated the prevalence of alternative splicing in multicellular eukaryotes, its key roles in determining tissue- and species-specific differentiation patterns, the multiple post- and co-transcriptional regulatory mechanisms that control it, and its causal role in hereditary disease and cancer. The emerging evidence places alternative splicing in a central position in the flow of eukaryotic genetic information, between transcription and translation, in that it can respond not only to various signalling pathways that target the splicing machinery but also to transcription factors and chromatin structure.Fil: Kornblihtt, Alberto Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Schor, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Alló, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Dujardin, Gwendal. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Petrillo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Muñoz, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Search for new physics in the dijet mass distribution using 1 fb⁻¹ of <i>pp</i> collision data at &#8730;s=7 TeV collected by the ATLAS detector

Invariant mass distributions of jet pairs (dijets) produced in LHC proton–proton collisions at a centre-of-mass energy &#8730;s=7  TeV have been studied using a data set corresponding to an integrated luminosity of 1.0 fb&lt;sup&gt;-1&lt;/sup&gt;recorded in 2011 by ATLAS. Dijet masses up to &#8764;4 TeV are observed in the data, and no evidence of resonance production over background is found. Limits are set at 95% C.L. for several new physics hypotheses: excited quarks are excluded for masses below 299 TeV, axigluons are excluded for masses below 3.32 TeV, and colour octet scalar resonances are excluded for masses below 1.92 TeV

Search for new physics in the dijet mass distribution using 1 fb(-1) of pp collision data at root s=7 TeV collected by the ATLAS detector

Invariant mass distributions of jet pairs (dijets) produced in LHC proton-proton collisions at a centre-of-mass energy root s = 7 TeV have been studied using a data set corresponding to an integrated luminosity of 1.0 fb(-1) recorded in 2011 by ATLAS. Dijet masses up to similar to 4 TeV are observed in the data, and no evidence of resonance production over background is found. Limits are set at 95% C.L. for several new physics hypotheses: excited quarks are excluded for masses below 299 TeV, axigluons are excluded for masses below 3.32 TeV. and colour octet scalar resonances are excluded for masses below 1.92 TeV. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved