Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 106 CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population

TL-dating applied to building archaeology: The case of the medieval church Notre-Dame-Sous-Terre (Mont-Saint-Michel, France)

The recent application of thermoluminescence (TL) dating to young building materials is being increasingly developed for use in the field of buildings archaeology. Ensuring the accuracy of the dating method is of the utmost importance in order to achieve results which are pertinent enough to have archaeological significance. This paper deals with an archaeological building study of the first church built on the Mont-Saint-Michel (France) and improvements made to the TL-protocol in Bordeaux. The aim is to achieve precise dates for the material under analysis and therefore, a better understanding of the evolution of the building. For this study, 14 bricks have been sampled from eight different masonries and submitted for TL dating analysis. With the exception of one sample which appears to be non-contemporaneous to the others, the date results range from 900 ± 80 to 1020 ± 60 AD. The results were then averaged according to the two phases established by the archaeological building study. The first two stages of the primitive church both date from the 10th century

Non-genetic Inheritance in Birds: transmission of behaviour from mother to offspring

Published under license CC-BY-NC-NDInternational audienceUnderstanding the mechanisms of non-genetic inheritance is fundamental as they are involved in evolution processes. One of the paths that nongenetic inheritance can take is via maternal effects. Indeed, we know that mammalian mothers can influence the general development of their offspring both before and after birth. In addition, maternal effects have recently been evidenced in avian species thus opening new possibilities to develop our knowledge of non-genetic inheritance mechanisms. Here, we review the literature on prenatal and postnatal maternal effects on bird behavioural development and we detail recent research that opens new perspectives concerning mechanisms involved in non-genetic inheritance

Prolonged thrombocytopenia after CAR T-cell therapy: the role of thrombopoietin receptor agonists

International audienceNo abstract availabl

Impact of diagnostic investigations in the management of CAR T-cell-associated neurotoxicity

International audienceInternational guidelines regarding the management of immune effector cell-associated neurotoxicity syndrome (ICANS) recommend several diagnostic investigations, including magnetic resonance imaging (MRI), lumbar puncture (LP), and electroencephalogram (EEG) based on ICANS grade. However, the impact of these investigations has not yet been evaluated. Here, we aimed to describe the role of MRI, LP, and EEG in the management of ICANS in a cohort of real-life patients treated with chimeric antigen receptor (CAR) T cells at the University Hospital of Rennes, France. Between August 2018 and January 2023, a total of 190 consecutive patients were treated with CAR T cells. Among those, 91 (48%) developed ICANS. MRI was performed in 71 patients (78%) with ICANS, with a therapeutic impact in 4% of patients, despite frequent abnormal findings. LP was performed in 43 patients (47%), which led to preemptive antimicrobial agents in 7% of patients, although no infection was eventually detected. Systematic EEG was performed in 51 patients (56%), which led to therapeutic modifications in 16% of patients. Our study shows that EEG is the diagnostic investigation with the greatest therapeutic impact, whereas MRI and LP appear to have a limited therapeutic impact. Our results emphasize the role of EEG in the current guidelines but question the need for systematic MRI and LP, which might be left to the discretion of the treating physician

Rituximab and DHAP followed by intensive therapy with autologous stem-cell transplantation as first-line therapy for mantle cell lymphoma.

International audienceWe report on a series of 24 patients with newly diagnosed mantle cell lymphoma treated with four to six courses of DHAP-rituximab followed by autologous stem cell transplantation for patients <65 years. Three-year overall survival (OS) and event free survival (EFS) rates were 69% and 65% respectively, for the 24 patients. In intent-to-treat analysis, 3-year OS and EFS were 75% and 76% for the 17 patients < 65 years old. This treatment is quite feasible and compares favourably with other regimens

Joint modeling of success and treatment discontinuation in <it>in vitro</it> fertilization programs: a retrospective cohort study

Abstract Background As discontinuation in in vitro fertilization (IVF) programs has been associated with a poor prognosis, one hypothesis is that some couple-specific predictive factors in IVF may be shared with opposite effect by both success (i.e. live birth) and treatment discontinuation processes. Our objective was to perform a joint analysis of these two processes to examine the hypothesis of a link between the two processes. Methods Analyses were conducted on a retrospective cohort of 3,002 women who began IVF between 1998 and 2002 in two French IVF centers: a Parisian center and a center in a medium-sized city in central France. A shared random effects model based on a joint modelization of IVF treatment success and discontinuation was used to study the link between the two processes. Results Success and discontinuation processes were significantly linked in the medium-sized city center, whereas they were not linked in the Parisian center. The center influenced risk of treatment discontinuation but not chance of success. The well-known inverse-J relation between the woman’s age and chance of success was observed, as expected. Risk of discontinuation globally increased as the woman’s age increased. Conclusions The link between success and discontinuation processes could depend on the fertility center. In particular, the woman’s decision to pursue or to discontinue IVF in a particular center could depend on the presence of other IVF centers in the surrounding area.</p

Joint modeling of success and treatment discontinuation in in vitro fertilization programs: a retrospective cohort study.

International audienceABSTRACT: BACKGROUND: As discontinuation in in vitro fertilization (IVF) programs has been associated with a poor prognosis, one hypothesis is that some couple-specific predictive factors in IVF may be shared with opposite effect by both successful (i.e. live birth) and treatment discontinuation processes. Our objective was to perform a joint analysis of these two processes to examine the hypothesis of a link between the two processes. METHODS: Analyses were conducted on a retrospective cohort of 3,002 women who began IVF between 1998 and 2002 in two French IVF centers: a Parisian center and a center in a medium-sized city in central France. A shared random effects model based on a joint modelization of IVF treatment success and discontinuation was used to study the link between the two processes. RESULTS: Success and discontinuation processes were significantly linked in the medium-sized city center, whereas they were not linked in the Parisian center. The center influenced risk of treatment discontinuation but not chance of success. The well-known inverse-J relation between the woman's age and chance of success was observed, as expected. Risk of discontinuation globally increased as the woman's age increased. CONCLUSIONS: The link between success and discontinuation processes could depend on the fertility center. In particular, the woman's decision to pursue or to discontinue IVF in a particular center could depend on the presence of other IVF centers in the surrounding area

Soluble HLA-G Molecules Are Increased during Acute Leukemia, Especially in Subtypes Affecting Monocytic and Lymphoid Lineages

Human leukocyte antigen G (HLA-G) molecules corresponding to nonclassic class I genes of the major histocompatibility complex exhibit immunomodulatory properties. They are either membrane-bound or solubly expressed during certain tumoral malignancies. Soluble human leukocyte antigen G (sHLA-G) molecules seem more frequently expressed than membrane-bound isoforms during hematologic malignancies, such as lymphoproliferative disorders. Assay of these molecules by enzyme-linked immunosorbent assay in patients suffering from another hematologic disorder (acute leukemia) highlights increased sHLA-G secretion. This increased secretion seems more marked in acute leukemia subtypes affecting monocytic and lymphoid lineages such as FABM4 and FABM5, as well as both B and T acute lymphoblastic leukemia (ALL). Moreover, this study uses in vitro cytokine stimulations and reveals the respective potential roles of granulocyte-macrophage colony-stimulating factor and interferon-γ in increasing this secretion in FABM4 and ALL. Correlations between sHLA-G plasma level and clinical biologic features suggest a link between elevated sHLA-G level and 1) the absence of anterior myelodysplasia and 2) high-level leukocytosis. All these findings suggest that sHLA-G molecules could be a factor in tumoral escape from immune survey during acute leukemia

Age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorders in elderly white patients.

International audienc