Efficacy and safety of once-weekly bortezomib in multiple myeloma patients

AbstractIn a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179

A prospective, multicenter study on hematopoietic stemcell mobilization with cyclophosphamide plus granulocyte colony-stimulating factor and ‘on-demand’ plerixafor in multiple myeloma patients treated with novel agents

High-dose melphalan plus autologous stem cell transplantation (ASCT) is a standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), and adequate hematopoietic stem cell (HSC) collection is crucial to ensure hematologic recovery after ASCT. In this prospective, observational study we evaluated HSC mobilization with granulocyte colony-stimulating factor (G-CSF), cyclophosphamide, and ‘on-demand’ plerixafor (in patients with 60% (odds ratio [OR]=4.14), lenalidomide use (OR=4.45), and grade 3-4 hematologic toxicities during induction (OR=3.53) were independently associated with a higher risk of mobilization failure or plerixafor need. Cyclophosphamide plus G-CSF and ‘on-demand’ plerixafor is an effective strategy in NDMM patients treated with novel agents, resulting in a high rate of HSC collection and high HSC yield (clinicaltrials gov. identifier: NCT03406091)

Performances des capteurs à fibre optique basés sur la diffusion Raman et Brillouin pour des mesures de températures et déformations en environnement sévère

This PhD thesis is conducted in the joint supervision of both the University Jean Monnet of Saint Etienne (France) and the University of Palermo (Italy) in collaboration with the French national agency for the management of radioactive wastes (ANDRA). The aim of the Thesis is to evaluate the performances of distributed optical fiber sensors (based on Raman and Brillouin scattering technologies) that will be employed for monitoring industrial site for deep geological disposal for high and long-lived intermediate level activity radioactive waste (HL-W and LL/IL-W, respectively), called Cigéo. In this context, the distributed optical fiber sensors will provide a time and spatial cartography of the strain and temperature inside the disposal cell. The severe environment of Cigéo requires the sensor evaluation taking into account the resulting degradation of the sensing optical fiber. The sensor response is affected by y-rays and hydrogen presences inside the storage cells. In both cases a decrease of the optical fiber transmission, due to the radiation or hydrogen induced attenuation (RIA or HIA) is observed and limits the sensing distance range of the sensor. Moreover, the two different environment constraints lead to errors in the temperature or strain evaluation for both sensor technologies. This Thesis work establishes the guidelines to select and design distributed optical fiber sensors suitable to operate in radiation environment such as Cigéo oneLa Thèse a été réalisée en cotutelle entre l’Université Jean Monnet de Saint Etienne (France) et l’université de Palerme (Italie) et en collaboration avec l’Agence nationale pour la gestion des déchets radioactifs (ANDRA). Le travail de recherche concerne l'étude des capteurs répartis à fibres optiques (utilisant la lumière rétrodiffusée Raman et Brillouin) destinés à l’observation et à la surveillance des ouvrages dédiés au stockage géologique de déchets radioactifs de haute activité et moyenne activité à vie longue (projet CIGEO : centre industriel de stockage géologique). Dans ce contexte, les fibres optiques sont envisagées en tant qu’élément sensible de capteurs pour la mesure de paramètres environnementaux tels que la température ou la déformation. Les conditions environnementales extrêmes d’exploitation entrainent la dégradation des propriétés de la fibre optique et des performances du capteur. La réponse des capteurs Brillouin et Raman est influencée par la présence de rayonnement y et d’hydrogène dans l’atmosphère Cigéo. Dans les deux cas, une diminution de la transmission linéique de la fibre optique est observée. Ce phénomène est dû à l’atténuation induite par radiation (RIA) ou par hydrogène (HIA) réduisant ainsi la portée de la mesure. En outre le rayonnement y et l’hydrogène provoquent des erreurs sur la mesure de température ou de déformation pour les deux types de capteurs. L’étude a permis d’établir les lignes directrices pour la sélection et le développement des capteurs repartis à fibre optique appropriés pour travailler dans l’environnement Cigé

Luminescence properties induced by sintering of silica nanoparticles

The effect of sintering on the optical properties of silica nanoparticles, a mean diameter of ~14 nm, are investigated by absorption and luminescence experiments. The sintering is induced by a thermal treatment of 1000 °C for 272 hours; after that the sample is transparent, and emits a bright luminescence under UV excitation. Time resolved photoluminescence spectra excited by a tunable laser source allows to evidence four bands around 2.0 eV, 2.4 eV, 2.7 eV and 3.4 eV, peculiar to defects induced by the sintering

Qualification of Electronic Systems for Radiation Environments of High Energy Accelerator

Unlike a typical Radiation Hardness Assurance (RHA) methodology, this work presents a system level radiation qualification of a complex electronic system prior to component radiation characterization tests. Such a top-down approach reduces the beam time needed for qualification of components by carefully analyzing failure modes observed on the system level and performing only a subset of component tests for identified cases. This avoids system overdesign, reduces the testing workload and cost by accepting a certain residual failure rate

Study of the impact of the LHC radiation environments on the Synergistic Displacement Damage and Ionizing Dose Effect on Electronic Components

International audienceBipolar-based components can exhibit a higher (or lower) degradation when exposed to both total ionizing dose (TID) and displacement damage (DD) effects simultaneously than the sum of the two separated effects. This paper investigates the implications of this synergistic effect on the radiation qualification process of large hadron collider’s (LHC’s) electronic equipment. More specifically, the impact of the wide range of DD/TID rate ratios of the LHC’s areas on the synergistic degradation rates is investigated. An analysis of the ratios of a crucial part of the accelerator is performed. A demonstration of the ability of the CHARM mixed-field facility of CERN to perform radiation tests in representative LHC’s ratios is also presented as well as radiation test results of a bipolar integrated circuit exposed to these different ratios are presented. Finally, the impact of this effect on the CERN radiation hardness assurance process is discussed and a simple method is proposed to qualify component against such effects

On-site Regeneration Technique for Hole-Assisted Optical Fibers Used In Nuclear Facilities

International audienceIn this paper, we demonstrate and highlight a proof of concept for the feasibility of an innovative technique to regenerate on-site irradiated optical fiber links in nuclear facilities. Using Hole-Assisted optical fibers (HAOF), a longitudinal gas-loading is easy to perform thanks to the fibers' dedicated holes located in the outer part of the cladding. All along the fiber length, gas ( H2 or D2) diffuses from the holes into the silica matrix, interacts with radiation induced point defects and passivates them, reducing the Radiation Induced Attenuation (RIA) levels. The validity of our approach is demonstrated considering the changes occurring at infrared wavelengths during the H2 treatment of a MGy irradiated single mode Ge-doped HAOF. Within just a few hours, a reduction of about 50% is observed for the RIA at 1550 nm of the 10 MGy irradiated HAOF, acting only from one of its two ends. An additional study is done on a set of fibers with various core dopants (F, Ge, P) and without holes to give an overview of the pertinence of developing HAOF fibers with these dopants for various applications. Using HAOF and this recovery technique appears very promising for samples based on pure-silica, Ge or F-doped cores and operating in the ultraviolet-visible spectral domains such as plasma diagnostics. This approach exhibits another interesting feature which may be extension to higher dose ranges and lifetime of P-doped distributed dosimeters used in high energy physics facilities or nuclear power plants

SEE Tests With Ultra Energetic Xe Ion Beam in the CHARM Facility at CERN

Taking advantage of the heavy ion acceleration program, tests on radiation effects with Ultrahigh Energy (UHE) xenon ion beams (with Energy > 5 GeV/nucleon) have been performed in several experimental areas of the CERN accelerator complex. Specifically, the outcomes of the first UHE heavy ion test campaign carried out at the CHARM facility are presented and discussed in this contribution. UHE ion beams have the advantage of not requiring a previous modification of the samples or testing in vacuum, owing to their large penetration range. The unique nature of the UHE ions motivated the study of their interaction with matter, with regard to the induction of SEE. To that end, great effort was paid on the calibration of the beam line instrumentation, typically prepared for the traditional proton runs. Electronic components sensitive to single event upset (SEU) and single-event latchup (SEL) were irradiated by an UHE xenon beam, with a particular interest in studying the sub-LET cross section region and benchmarking against the standard heavy ion test beams. Finally, the suitability of UHE ion testing for Radiation Hardness Assurance is also discussed in the contribution