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Summary: The meeting focused in particular on new strategies such as chimeric antigen receptor (CAR)-T cells and bispecific antibodies. Updates of clinical trials regarding induction treatment in transplantable and non-transplantable status were presented. Furthermore, minimal residual disease negativity (MRD) or, in other words, a status characterized by no measurable disease, using standardized multicolor-flow cytometry or next-generation sequencing techniques becomes increasingly important as an endpoint in clinical trials. A subjectively assessed overview of the current contributions to the treatment of multiple myeloma is given here. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma is a highly curable disease. Although most patients achieve complete response following frontline therapy, key unmet clinical needs remain including relapsed/refractory disease, treatment-related morbidity, impaired quality of life and poor outcome in patients older than 60 years. The incorporation of novel therapies, including check point inhibitors and antibody–drug conjugates, into the frontline setting, sequential approaches, and further individualized treatment intensity may address these needs. We summarize the current treatment options for patients with classical Hodgkin lymphoma from frontline therapy to allogeneic hematopoietic stem cell transplantation and describe novel trials in the field. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed. Results: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events. Conclusion: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1. Clinical trial registration: NCT02761187 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Purpose: The preferred hypothesis for the dissemination patterns of Hodgkin lymphoma (HL) is the contiguity hypothesis. However, this hypothesis is based on studies performed before the advent of [ 18 F]-FDG PET/CT which is now the established reference for HL staging. This study aims to extract the dissemination patterns of HL using [ 18 F]-FDG PET/CT and a probability network model., Methods: We retrospectively analyzed [ 18 F]-FDG PET/CT performed for initial staging of patients with classical HL. The HL involvement status (presence of absence) was reported for 19 supra- and infra-diaphragmatic lymph node regions and 4 extranodal regions (lung, spleen, liver, and osteo- medullary). The analysis of HL dissemination was carried out using HL involvement status for all regions through 3 distinct methods: comparison of nearby lymph node regions, correlation assessment between all regions and relationship strength between all regions using Ising network model., Results: A total of 196 patients were included. Our results showed strong relationships between nearby involved lymph node regions (for example between the left pelvic and the abdominal lymph node regions (relationship strength = 0.980)) and between more distant regions (for example between right and left axillary lymph node regions (strength = 0.714)). Furthermore, involvement of the infra-diaphragmatic lymph node regions was significantly correlated with Ann Arbor stage IV (phi = 0.56, p < 0.001)., Conclusion: This study confirms the hypothesis of lymphatic dissemination of HL in a contiguous mode, with additional links between more distant regions. These predictable dissemination patterns could be useful for the initial staging assessment of patients with HL using [ 18 F]-FDG PET/CT., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Résumé: Si le pronostic du myélome multiple a été nettement amélioré par le développement des inhibiteurs du protéasome et des immunomodulateurs, la maladie reste incurable et la durée de survie est de l'ordre de cinq ans chez les patients non éligibles à la greffe. Le second tournant dans l'histoire des thérapeutiques du myélome est sans nul doute l'arrivée de l'immunothérapie, dont l'activité permet notamment de restaurer des fonctions immunitaires antitumorales. Les anticorps monoclonaux anti-CD38 s'associent particulièrement bien aux immunomodulateurs : leur synergie permet des réponses durables et cette combinaison devient la nouvelle référence des patients nouvellement diagnostiqués non éligibles à la greffe. Si le myélome est en soi associé à une diminution des fonctions immunitaires (dysfonction des lymphocytes B, T et NK, ainsi que des cellules dendritiques mais également action de cellules T régulatrices et de cellules myéloïdes suppressives), le vieillissement participe également à l'immunosénescence. Le ciblage thérapeutique du système immunitaire paraît par conséquent particulièrement intéressant dans le contexte des sujets âgés. Une meilleure connaissance des mécanismes de la dysfonction immunitaire antitumorale est nécessaire pour optimiser l'utilisation de l'immunothérapie dans l'arsenal des médicaments du myélome. While the prognosis of multiple myeloma has been significantly improved by the development of proteasome inhibitors and immunomodulators, the disease remains incurable and the survival time is around five years in patients not eligible for transplantation. The second turning point in the history of myeloma therapies is undoubtedly the arrival of immunotherapy, whose activity notably restores anti-tumor immune functions. The anti-CD38 monoclonal antibodies combine particularly well with immunomodulators: their synergy allows lasting responses and this combination becomes the new benchmark for newly diagnosed patients not eligible for transplantation. If myeloma is in itself associated with a decrease in immune functions (dysfunction of B, T and NK lymphocytes, as well as dendritic cells but also action of regulatory T cells and suppressive myeloid cells), aging also participates in the immune system. - senescence. Therapeutic targeting of the immune system therefore appears to be particularly advantageous in the context of the elderly. A better understanding of the mechanisms of anti-tumor immune dysfunction is necessary to optimize the use of immunotherapy in the arsenal of myeloma drugs. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) diagnostics and therapeutics have improved dramatically over the past two decades, with increased adoption of advanced imaging techniques, improved prognostic risk stratification tools, including fluorescence in situ hybridization (FISH) studies and minimal residual disease (MRD) testing, and the development of highly effective novel agents including next-generation immunomodulatory drugs (IMIDs), proteasome inhibitors (PIs), and monoclonal antibodies (MoABs). Daratumumab-based maintenance strategies are currently under investigation and may be utilized for patients who receive daratumumab as part of induction therapy. As the guidelines correctly emphasize, the role of ASCT in MM remains an integral part of therapy for transplant-eligible patients, based on the improvement in PFS demonstrated in the IFM/DFCI 2009 trial, as well as multiple other studies. However, specific agents or treatment modalities may not be appropriate for certain patients. [Extracted from the article]

In this study, we deal with the neutron flux monitoring inside the TRIGA MARK II reactor as one of the nonnegative matrix factorization problems. The fact that these methods of separating blind sources does not require any assumptions on the way the signal and noise were mixed has encouraged us to apply them to online neutron flux monitoring through neutron-gamma discrimination. We synthesize fission chambers output signals using the Python-based Fission Chamber simulator (pyFC). These signals are then considered as time series mixtures that are analyzed through nonnegative algorithms known as the most popular blind source separation techniques to extract original sources signals. The obtained results show that the Regularized Lee–Sung algorithm is the most appropriate method for discriminating neutrons and gammas. Furthermore, the neutron-gamma discrimination is highlighted through the computation of the cross-correlation functions between the separated source signals and pure neutron and gamma signals. The presented method provides a better characterization of the neutron and gamma signals with very high accuracy. [ABSTRACT FROM AUTHOR]

We evaluated the outcomes of 168 patients undergoing delayed or second autologous stem cell transplant (ASCT) for relapsed multiple myeloma (MM) from 2010 to 2019. Overall, 21% (n = 35) patients had received a prior transplant and 69% (n = 116) underwent transplant at first relapse. Overall, 27% patients had high-risk cytogenetics and 15% had ISS stage III disease. Stem cell collection was performed after relapse in 72% and 35% of patients received maintenance therapy. Median PFS from salvage treatment and transplant were 28 and 19 months, respectively. Median OS from salvage treatment and transplant was 69 and 55 months. Multivariate analysis revealed that ASCT in first relapse was associated with superior PFS (HR 0.63, p = 0.03) and OS (HR 0.59, p = 0.04) compared to later lines of therapy. In addition, PFS of ≥36 months with prior therapy was associated with improved PFS (HR 0.62, p = 0.04) and OS (HR 0.41, p = 0.01). Ninety-five patients underwent delayed transplant at first relapse, median PFS and OS from start of therapy was 30 and 69 months, and median OS from diagnosis was 106 months. These data may serve as a guide when counseling patients undergoing ASCT for relapsed MM and provide a benchmark in designing clinical trials of transplantation/comparative treatments for relapsed MM., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The ANIMMA conferences offer a unique opportunity to discover research carried out in all fields of nuclear measurements and instrumentation with applications extending from fundamental physics to fission and fusion reactors, medical imaging, environmental protection and homeland security. After four successful editions of the Conference, it was decided to prepare a review based to a large extent but not exclusively on the papers presented during the first four editions of the conference. This review is organized according to the measurement methodologies: neutronic, photonic, thermal, acoustic and optical measurements, as well as medical imaging and specific challenges linked to data acquisition and electronic hardening. The paper describes the main challenges justifying research in these different areas, and summarizes the recent progress reported. It offers researchers and engineers a way to quickly and efficiently access knowledge in highly specialized areas. [ABSTRACT FROM AUTHOR]

Presents the table of contents for this issue of the periodical. [ABSTRACT FROM PUBLISHER]

The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS). The availability of techniques such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment allowed the design of MRD-based response-adjusted trials that will define, in particular, the role of consolidation and maintenance therapies. In this review, we will provide an overview of the most recent evidence and the future prospects of ASCT in MM patients. [ABSTRACT FROM AUTHOR]

Online nuclear measurements inside experimental channels of material testing reactors (MTRs) are needed for experimental works (to design mock-ups) and for numerical works (input data) in order to better understanding complex phenomena occurring during the accelerated ageing of materials and the irradiation of nuclear fuels. In this paper, we focus only on one kind of measurements: nuclear heating performed by means of a radiometric calorimeter. The aims of numerical and experimental works are firstly to optimize the sensor response: in particular the sensitivity for new energy deposit ranges (new lower nuclear heating level in the reflector), and then to miniaturize and adapt this sensor for irradiation conditions in the Jules Horowitz Reactor (JHR). A calorimeter, developed previously by the CEA, is studied. It corresponds to a graphite differential calorimeter. It is used with a nonadiabatic mode called heat flow mode too. Experimental calibration of the sample cell is presented. In that case, energy deposit is simulated by Joule effect and the sample cell is inserted into a bath at a regulated temperature and controlled flow. The response of the sensor is discussed versus electrical power imposed for two flow rates. Numerical works show the influence of the gas conductivity and of specific dimensions on the cell sensitivity. [ABSTRACT FROM AUTHOR]

High temperature fission chambers are key instruments for the control and protection of the sodium-cooled fast reactor. First, the developments of those neutron detectors, which are carried out either in France or abroad are reviewed. Second, the French realizations are assessed with the use of the technology readiness levels in order to identify tracks of improvement. [ABSTRACT FROM AUTHOR]

For the on-line monitoring of high fast neutron fluxes in the presence of a strong thermal neutron component, SCK•CEN and CEA are jointly developing a Fast Neutron Detector System, based on ^242\ Pu fission chambers as sensors and including dedicated electronics and data processing systems. Irradiation tests in the BR2 reactor of ^242\ Pu fission chambers operating in current mode showed that in typical MTR conditions the fission chamber currents are dominated by the gamma contribution. In order to reduce the gamma contribution to the signal, it was proposed to use the fission chambers in Campbelling mode. An irradiation experiment in the BR2 reactor with a ^242\ Pu and a ^235\ U fission chamber, both equipped with a suitable cable for measurements in Campbelling mode, proved the effectiveness of the suppression of the gamma-induced signal component by the Campbelling mode: gamma contribution reduction factors of 26 for the ^235\ U fission chamber and more than 80 for the ^242\ Pu fission chamber were obtained. The experimental data also prove that photofission contributions are negligibly small. Consequently, in typical MTR conditions the gamma contribution to the fission chamber Campbelling signal can be neglected. [ABSTRACT FROM AUTHOR]

Flux monitoring is of great interest for experimental studies in material testing reactors. Nowadays, only the thermal neutron flux can be monitored on line, e.g., using fission chambers or self-powered neutron detectors. In the framework of the Joint Instrumentation Laboratory between SCK-CEN and CEA, we have developed a fast neutron detector system (FNDS) capable of measuring on line the local high-energy neutron flux in fission reactor core and reflector locations. FNDS is based on fission chambers measurements in Campbelling mode. The system consists of two detectors, one detector being mainly sensitive to fast neutrons and the other one to thermal neutrons. On line data processing uses the CEA depletion code DARWIN in order to disentangle fast and thermal neutrons components, taking into account the isotopic evolution of the fissile deposit. The first results of FNDS experimental test in the BR2 reactor are presented in this paper. Several fission chambers have been irradiated up to a fluence of about 7 × 1020 n/cm2. A good agreement (less than 10% discrepancy) was observed between FNDS fast flux estimation and reference flux measurement. [ABSTRACT FROM AUTHOR]

Optimizing the life cycle of nuclear systems under safety constraints requires high-performance experimental programs to reduce uncertainties on margins and limits. In addition to improvement in modeling and simulation, innovation in instrumentation is crucial for analytical and integral experiments conducted in research reactors. [ABSTRACT FROM AUTHOR]

Fission chambers are widely used in the nuclear industry. As an example, they play a major role in the control of any fission reactor and are thus regarded as a key component for ensuring their safety. They are also employed in the material testing reactors for monitoring irradiations. We have recently started a research program, the objective of which is to improve the performance of those neutron detectors in terms of lifetime, calibration, and online diagnosis. In this paper, we present several studies carried out in order to model the signal delivered by a fission chamber. First, the simulation of the deposit evolution allowed us to select the most appropriate fissile material for a given spectrum and fluence. Second, we studied the impact of the bias voltage and filling gas characteristics on the charge collection time. Finally, the simulation of a pulse signal prior to amplification showed how it is important to have a satisfactory knowledge of the energy for creating ion pairs to accurately assess the signal in current or Campbelling mode. [ABSTRACT FROM AUTHOR]

This paper continues the publication of the "SPARK 2014 Rationale", which started in the December 2013 issue of the Ada User Journal. In this instalment, we present three contributions regarding ghost code, Object Oriented programming and functional update in SPARK. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review we have summarized the history, the current use, and the future possibilities of alkylator treatment in multiple myeloma. Alkylators have for decades been part of the standard of care of myeloma treatment, but still new alkylators and new use of old alkylators are making its way into myeloma guidelines of today. A large number of novel treatments for myeloma have been developed and approved; however, alkylating drugs continue to be part of standard regimens. Additionally, novel alkylators are currently being developed. We performed a non-systematized literary search for relevant papers and communications at large conferences, as well as exploiting the authors' knowledge of the field, to review the history, current use and novel concepts around the traditional alkylators cyclophosphamide, bendamustine and melphalan and current data on the newly developed pro-drug melflufen. Even in the era of targeted treatment and personalized medicine, alkylating drugs continue to be part of the standard-of-care in myeloma, and new alkylators are coming to the market. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this review is to provide an overview of the current scientific evidence concerning the role of stem cell transplantation in multiple myeloma. During the past decade, several new treatment options have become available, thereby questioning the role of stem cell transplantation for the management of multiple myeloma. This review focuses on these studies, demonstrating a benefit for autologous stem cell transplantation (auto-SCT). We also reviewed maintenance post auto-SCT and utility of allogeneic stem cell transplant. Autologous stem cell transplantation (auto-SCT) has been the standard of care in eligible newly diagnosed multiple myeloma (MM) patients. Outcomes of patients with MM have improved significantly due to the advent of several novel drugs. Upfront use of these drugs in induction therapy has significantly increased the rate and depth of responses that have translated into longer remission and survival. This has now raised a debate regarding the role and relevance of auto-SCT in the management of myeloma. However, clinical trials have confirmed the utility of auto-SCT even in the era of novel drugs. Tandem auto-SCT followed by maintenance has shown a progression-free survival (PFS) benefit in high-risk MM, and hence can be considered in young and fit patients with high-risk disease. Auto-SCT has the advantages of resetting the bone marrow microenvironment, short-lived toxicity compared to the long-term physical and financial toxicities of continued chemotherapy in the absence of SCT, very low transplant-related mortality (TRM) in high volume centers, and providing longer disease-free survival when followed by maintenance therapy. Allogeneic SCT is one potentially curative option for MM, albeit with an increased risk of death due to high TRM. Strategies to modulate the graft-versus-host disease (GVHD) while maintaining or improving the graft-versus-myeloma (GVM) effect could place allogeneic SCT back in the treatment armamentarium of MM. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) is a well-established approach to treatment of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) recommended by both the European Society for Medical Oncology and the National Comprehensive Cancer Network based on the results from randomized controlled studies. However, a considerable number of patients who receive ASCT will progress/relapse and display suboptimal post-transplant outcomes. Over recent years, a number of different strategies have been assessed to improve post-ASCT outcomes and augment HL cure rates. These include use of pre- and post-ASCT salvage therapies and post-ASCT consolidative therapy, with the greatest benefits demonstrated by targeted therapies, such as brentuximab vedotin. However, adoption of these new approaches has been inconsistent across different centers and regions. In this article, we provide a European perspective on the available treatment options and likely future developments in the salvage and consolidation settings, with the aim to improve management of patients with HL who have a high risk of post-ASCT failure. CONCLUSIONS: We conclude that early intervention with post-ASCT consolidation improves outcomes in patients with R/R HL who require ASCT. Future approvals of targeted agents are expected to further improve outcomes and provide additional treatment options in the coming age of personalized medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: The approach to relapsed and refractory classical Hodgkin lymphoma is rapidly evolving. Over the past five years, we have seen the arrival of novel immunotherapies with impressive clinical response rates. These agents are actively being investigated earlier in the sequence of therapies and in combination with other clinically active therapies. We are also witnessing the arrival of new therapies for multiply relapsed disease such as chimeric antigen receptor T-cell therapy, which holds immense promise for patients in the future. This review aims to provide an overview of recent updates to both the standard of care and investigational approaches for patients with relapsed and refractory classical Hodgkin lymphoma. Hodgkin lymphoma (HL) is a B-cell malignancy representing approximately one in ten lymphomas diagnosed in the United States annually. The majority of patients with HL can be cured with chemotherapy; however, 5–10% will have refractory disease to front-line therapy and 10–30% will relapse. For those with relapsed or refractory (r/r) HL, salvage chemotherapy followed by autologous stem cell transplant (ASCT) is standard of care, but half of patients will subsequently have disease progression. Relapse following ASCT has been associated with exceedingly poor prognosis with a median survival of only 26 months. However, in recent years, novel agents including brentuximab vedotin (BV) and programmed cell death protein 1 monoclonal antibodies (anti-PD-1, nivolumab and pembrolizumab) have been shown to extend overall survival in r/r HL. With the success of novel agents in relapsed disease after ASCT, these therapies are beginning to show clinically meaningful response rates prior to ASCT. Finally, a new investigation in r/r HL continues to produce promising treatment options even after ASCT including CD30 directed chimeric antigen receptor T-cell therapy. In this review, we will discuss the recent advances of BV and anti-PD-1 therapy prior to ASCT, novel approaches in r/r HL after ASCT, and review active clinical trials. [ABSTRACT FROM AUTHOR]