Incidence, prognostic impact and clinical outcomes of renal impairment in patients with multiple myeloma: a population-based registry

BACKGROUND: Renal impairment (RI), a severe complication in multiple myeloma (MM), is considered as a poor prognostic factor. Patient survival has increased with the use of novel drugs and autologous stem-cell transplantation (ASCT). However, specific evolution of the incidence of RI in MM and its impact on prognosis remain unclear. METHODS: Using a population-based registry of 1038 newly diagnosed MM in Gironde, France, we evaluated the incidence trends of RI in MM patients and assessed net survival according to factors of interest using Pohar-Perme indicator and excess mortality rate regression. We also reviewed 114 cases of MM with RI to describe their clinical outcomes. RESULTS: In our population-based study, 24.6% of MM patients presented with RI (12.9% required haemodialysis). Median survival time was 21 months in patients with RI versus not reached at 3 years for other patients (P 73 years, RI, comorbidities and non-use of drugs or ASCT were associated with excess mortality risk. The effect of RI on excess mortality rates was maximum in the first 6 months after diagnosis. In the observational study, median follow-up time was 22.5 months; factors associated with renal response were haematologic response [odds ratio (OR) 6.81; P < 0.01] and previous chronic kidney disease (OR 0.26; P = 0.04). Factors associated with 1-year overall survival were haematological [hazard ratio (HR) 0.13; P < 0.01] and renal response (HR 0.27; P = 0.03). CONCLUSIONS: RI represents an independent negative prognostic factor in MM in the first 6 months after diagnosis. Renal recovery and haematologic response are the strongest markers associated with patient survival

Passive environmental residential exposure to agricultural pesticides and hematological malignancies in the general population: a systematic review

Incidence rates of hematological malignancies have been constantly increasing over the past 40 years. In parallel, an expanding use of agricultural pesticides has been observed. Only a limited number of studies investigated the link between hematological malignancies risk and passive environmental residential exposure to agricultural pesticides in the general population. The purpose of our review was to summarize the current state of knowledge on that question. A systematic literature search was conducted using PubMed and Scopus databases. We built a scoring scale to appraise relevance of each selected articles. We included 23 publications: 13 ecological studies, 9 case-control studies and a cohort study. Positive associations were reported between hematological malignancies and individual pesticides, pesticide groups, all pesticides without distinction, or some crop types. Relevance score was highly various across studies regardless of their design. Children studies were the majority and had overall higher relevance scores. The effect of passive environmental residential exposure to agricultural pesticides on hematological malignancies risk is suggested by the literature. The main limitation of the literature available is the high heterogeneity across studies, especially in terms of exposure assessment approach. Further studies with high methodological relevance should be conducted

Second- or third-generation tyrosine kinase inhibitors in first-line treatment of chronic myeloid leukemia in general population: Is there a real benefit?

International audienceINTRODUCTION: Since 2009, multiple randomized trials have shown faster and deeper responses in CML patients treated with new-generation TKI (NG-TKI) compared to those treated with imatinib (IM). Are the same results observed in the general population?MATERIALS AND METHODS: Patients were identified from the three French hematological malignancies population-based registries. All CML patients (ICD-O-3: 9875/3) diagnosed between 2006 and 2016 and resided in registries areas were included. The TKI generation effect on achievement of MMR in first-line therapy was assessed through a multivariate competitive risk analysis. An alluvial plot described the pathways leading to death.RESULTS: In total, 507 CML patients received TKI in first-line treatment, 22% were enrolled in a clinical trial. After adjustment, NG-TKI patients were significantly more likely to achieve MMR during first-line therapy than IM patients (HR: 1.88 CI95% [1.35-2.61]). At the end of follow-up, 212 patients were still in first-line therapy (46 of them died), 203 switched to second-line (43 subsequently died), 26 were on TFR from first-line (4 subsequently died), and 20 stopped their treatment (16 subsequently died).DISCUSSION: In this comprehensive real-life setting, the results were consistent with clinical trials. The results are not sufficient to conclude that a NG-TKI treatment is superior with regard to these patients, despite indications regarding differences between the TKI generation effect on survival and tolerance

Saraf-Phase II: Test of the SRF Cavities with the First Cryomodule

International audienceCEA is committed to delivering a Medium Energy Beam Transfer line and a superconducting linac (SCL) for SARAF accelerator in order to accelerate 5 mA beam of either protons from 1.3 MeV to 35 MeV or deuterons from 2.6 MeV to 40 MeV. The SCL consists in four cryomodules. The first cryomodule hosts 6 half-wave resonator (HWR) low beta cavities (β = 0.09) at 176 MHz. The low-beta cavities were qualified in 2021, as well as the power couplers and frequency tuners. The Low-Level RF (LLRF) system was qualified in 2022 with a dedicated test stand. This contribution will present the results of the RF tests of the first SARAF cryomodule at Saclay

Machine Protection System at SARAF

International audienceCEA Saclay Irfu is in charge of the major part of the control system of the SARAF-LINAC accelerator based at Soreq in Israel. This scope also includes the Machine Protection System. This system prevents any damage in the accelerator by shutting down the beam in case of detection of risky incidents like interceptive diagnostics in the beam or vacuum or cooling defects. So far, the system has been used successfully up to the MEBT. It will be tested soon for the super conducting Linac consisting of 4 cryomodules and 27 cavities. This Machine Protection System relies on three sets: the MRF timing system that is the messenger of the "shut beam" messages coming from any devices, IOxOS MTCA boards with custom FPGA developments that monitor the Section Beam Current Transmission along the accelerator and a Beam Destination Master that manages the beam destination required. This Destination Master is based on a master PLC. It permanently monitors Siemens PLCs that are in charge of the "slow" detection for fields such as vacuum, cryogenic and cooling system. The paper describes the architecture of this protection system and the exchanges between these three main parts