Deep-Learning Assessed Muscular Hypodensity Independently Predicts Mortality in DLBCL Patients Younger Than 60 Years.

[en] BACKGROUND: Muscle depletion (MD) assessed by computed tomography (CT) has been shown to be a predictive marker in solid tumors, but has not been assessed in non-Hodgkin's lymphomas. Despite software improvements, MD measurement remains highly time-consuming and cannot be used in clinical practice. METHODS: This study reports the development of a Deep-Learning automatic segmentation algorithm (DLASA) to measure MD, and investigate its predictive value in a cohort of 656 diffuse large B cell lymphoma (DLBCL) patients included in the GAINED phase III prospective trial (NCT01659099). RESULTS: After training on a series of 190 patients, the DLASA achieved a Dice coefficient of 0.97 ± 0.03. In the cohort, the median skeletal muscle index was 50.2 cm2/m2 and median muscle attenuation (MA) was 36.1 Hounsfield units (HU). No impact of sarcopenia was found on either progression free survival (PFS) or overall survival (OS). Muscular hypodensity, defined as MA below the tenth percentile according to sex, was associated with a lower OS and PFS, respectively (HR = 2.80 (95% CI 1.58-4.95), p < 0.001, and HR = 2.22 (95% CI 1.43-3.45), p < 0.001). Muscular hypodensity appears to be an independent risk factor for mortality in DLBCL and because of DLASA can be estimated in routine practice

Advances in the therapy of Alzheimer's disease: Targeting amyloid beta and tau and perspectives for the future

Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD

IMMUNOSELECTION POSITIVE DES CELLULES CD34+ CIRCULANTES EN THERAPIE CELLULAIRE (SPECIFICITES DU CONTROLE DE QUALITE DES PROGENITEURS CLONOGENIQUES)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

IMMUNOSELECTION POSITIVE DES CELLULES CD34+ CIRCULANTES EN THERAPIE CELLULAIRE. SPECIFICITE DU CONTROLE DE QUALITE DES PROGENITEURS CLONOGENIQUES(DES)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Taux élevé de réponse complète (RC) avec maladie résiduelle (MRD) indétectable dans la moelle après une stratégie d’épargne de chimiothérapie guidée par la MRD en première ligne de traitement dans la leucémie lymphoïde chronique (LLC)

# 04-05International audienc

Enseigner les sciences sociales de l'environnement

En réponse à une croissance soutenue des enjeux environnementaux, les demandes de la part des instances, des associations, des institutions d'enseignement et surtout, des étudiants pour des cours soit sur l'environnement soit qui intègrent les problématiques environnementales. La demande étudiante notamment dépasse, en effet, l'offre des programmes dans trop de nos institutions d'enseignement. Les changements climatiques, la crise de l'eau, les déchets et la pollution font dorénavant de l'enseignement relatif à l'environnement une nécessité de plus en plus urgente. Ce livre, un des premiers en langue française dans ce domaine, réunit une équipe internationale et multidisciplinaire d'enseignants-chercheurs issue des sciences sociales. Il offre des activités, des méthodes et des cours complets aux enseignants pour former les apprenants aux problématiques de l'environnement et du développement durable. Il vise à contribuer à la constitution de cursus pluridisciplinaires sur la question environnementale en cours dans nos universités. Les activités décrites ici ont toutes fait leur preuve dans des conditions d'enseignement réelles et elles sont présentées de telle sorte que l'enseignant puisse les reproduire et les utiliser en classe

Obinutuzumab and idelalisib in symptomatic patients with relapsed/refractory Waldenström macroglobulinemia

International audienceWe present the results of a phase 2 study evaluating the combination of obinutuzumab + idelalisib in relapsed/refractory (R/R) Waldenström macroglobulinemia (WM). The goal was to determine the safety and efficacy of a fixed-duration chemotherapy-free treatment. During the induction phase, patients received idelalisib + obinutuzumab for 6 cycles, followed by a maintenance phase with idelalisib alone for ≤2 years. Forty-eight patients with R/R WM were treated with the induction combination, and 27 patients participated in the maintenance phase. The best responses, reached after a median of 6.5 months (interquartile range, 3.4-7.1; range, 2.6-22.1 months), were very good partial response in 5 patients, partial response in 27 patients, and minor response in 3 patients, leading to overall response rate and major response rate estimates of 71.4% (95% confidence interval [CI], 56.7-83.4) and 65.3% (95% CI, 50.4-78.3), respectively. With a median follow-up of 25.9 months, median progression-free survival was 25.4 months (95% CI, 15.7-29.0). Univariate analysis focusing on molecular screening found no significant impact of CXCR4 genotypes on responses and survivals but a deleterious impact of TP53 mutations on survival. Although there was no grade 5 toxicity, 26 patients were removed from the study because of side effects; the most frequent were neutropenia (9.4%), diarrhea (8.6%), and liver toxicity (9.3%). The combination of idelalisib + obinutuzumab is effective in R/R WM. Nonetheless, the apparent lack of impact of genotype on outcome could give new meaning to targeting of the phosphatidylinositol 3-kinase pathway in WM. This trial was registered at www.clinicaltrials.gov as #NCT02962401

Anti-CD19 CAR T-Cell Therapy for Patients with Richter Syndrome: A Lysa Study from the Descar-T Registry

International audienceBackground Richter syndrome (RS) refers to the onset of aggressive lymphoma, mostly diffuse large B-cell lymphoma (DLBCL), in patients with chronic lymphocytic leukemia (CLL). The outcome of RS patients is usually very poor with short survival (typically 2. Tocilizumab was administered to 9 (75%) patients. Five (42%) patients had ICANS, 3 (25%) with grade > 3. Regarding hematotoxicity, 6 (50%) patients presented with grade > 2 thrombocytopenia, 5 (42%) with grade > 2 anemia, and 7 with (58%) grade > 2 neutropenia. One case of macrophage activation syndrome was reported. Three patients were admitted to intensive care. A total of 5 (42%) patients had infections. After a median follow-up of 1.6 months (range, 0-23), 8 (67%) patients were alive, 4 (33%) patients died (2 from CRS and 2 from disease progression).Conclusions CD19-directed CAR T-cell therapy showed high response rates in our series of heavily pretreated RS patients. Frequency of CAR T-cell-specific adverse events was in the range of what is observed in de novo DLBCL while severity appeared higher (Schuster et al., NEJM 2019; Neelapu et al., NEJM 2017). Larger cohort with longer follow-up and prospective trials are warranted to confirm these observations