Dasatinib in First- and Second-Line Therapy of Chronic Myeloid Leukemia: Efficacy, Safety and Quality of Life

Background & Aims. The article presents results of two observational, prospective, multicenter studies “Quality of Life, Symptom Profile, and Adherence to Treatment in Adult Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Receiving Dasatinib” (2012–2015) and “Quality of Life and Symptom Profile in Imatinib-Resistant or Intolerant Patients with Chronic Myeloid Leukemia” (2011–2014). Methods. Data of 107 patients with chronic myeloid leukemia in chronic phase were involved in the real-world analysis — 32 newly diagnosed patients on first-line treatment with dasatinib or after yearly switch to dasatinib after imatinib treatment failure and 75 imatinib-resistant or intolerant patients on second-line treatment with dasatinib. Treatment effectiveness and safety of dasatinib were assessed during first and second-line dasatinib treatment using clinical outcomes as well as quality of life and symptom profile assessment. Results. The real-world data obtained during observational study in limited population of CML patients conform the results of clinical trials devoted to evaluation of treatment efficacy and safety of dasatinib treatment in first and second-line treatment and demonstrate the importance of patient-reported outcomes. Patient’s quality of life improved within 12 months of the first-line dasatinib therapy according to the following scales: role physical functioning, pain, vitality, social functioning and role emotional functioning. The most pronounced and clinically significant improvement was observed for the role emotional functioning (51.1 vs. 68.9). During the second-line dasatinib treatment, stabilization of quality of life parameters was registered for the following scales: vitality, social functioning, mental health, and pain. Significant improvement of the Integral Quality of Life Index was observed (p < 0.05). Positive dynamics of relevant symptoms was registered. The symptom severity decreased during both the first and second-line therapy. Conclusion. Quality of life and symptom assessment in CML patients contribute to a better disease control in accordance with the principles of risk-adaptive therapy

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Stable electron beams from laser wakefield acceleration with few-terawatt driver using a supersonic air jet

International audienceThe generation of stable electron beams produced by the laser wakefield acceleration mechanism with a few-terawatt laser system (600 mJ, 50 fs) in a supersonic synthetic air jet is reported and the requirements necessary to build such a stable electron source are experimentally investigated in conditions near the bubble regime threshold. The resulting electron beams have stable energies of (17.4 +/- 1.1) MeV and an energy spread of (13.5 +/- 1.5) MeV (FWHM), which has been achieved by optimizing the properties of the supersonic gas jet target for the given laser system. Due to the availability of few-terawatt laser systems in many laboratories around the world these stable electron beams open possibilities for applications of this type of particle source

Overview of Development of Laser Driven Secondary Sources at PALS and ELI

International audienceIn this paper we report on development of the secondary X-ray sources at the PALS Centre and discuss the plan for the ELI Beamlines project. The spatial and temporal coherence of the most energetic quasi-steady state Ne-like Zn X-ray laser, which is operated at PALS Centre as standard user beamline, was examined proving that amplification of coherent EUV pulses with duration below 1 ps will be possible. Meanwhile, the first transient lasing at PALS Center was achieved using 10 Hz Ti: Sapphire laser chain with peak power of 20 TW as a driver. Finally, we discuss the recent design of laser driven secondary sources generating short coherent or incoherent EUV/X-ray pulses within the ELI Beamlines project

Pump requirements for betatron-generated femtosecond X-ray laser at saturation from inner-shell transitions

International audienceWe study pump requirements to produce femtosecond X-ray laser pulses at saturation from inner-shell transitions in the amplified spontaneous emission regime. Since laser-based betatron radiation is considered as the pumping source, we first study the impact of the driving laser power on its intensity. Then we investigate the amplification behavior of the K-a transition of nitrogen at 3.2 nm (395 eV) from radiative transfer calculations coupled with kinetics modeling of the ion population densities. We show that the saturation regime may be experimentally achieved by using PW-class laser-accelerated electron bunches. Finally, we show that this X-ray laser scheme can be extended to heavier atoms and we calculate pump requirements to reach saturation at 1.5 nm (849 eV) from the K-a transition of neon. © Springer-Verlag 2012