Immune Reconstitution following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation: The Impact of Expanding CD28negative CD8+ T Cells on Relapse

AbstractAllogeneic stem cell transplantation has become standard therapy for hematologic malignancies through the positive immunologic graft-versus-leukemia effect. Initial immune recovery relies on peripheral expansion of infused T cells, which switch to a memory-like phenotype. This study prospectively investigated whether changes in subset composition precedes complications after myeloablative HLA-matched transplantation for hematologic malignancies. Of 80 allograft recipients, 18 were still free of clinical complication throughout 395 to 1564 days of follow-up. Compared with this complication-free subgroup, patients who developed chronic graft-versus-host disease (cGVHD) without relapsing recovered similar numbers of circulating T cells with predominance of CD8+ T cells lacking CC-chemokine receptor-7 and CD28 expression throughout the first year after transplantation. Conversely, poor CD8+ T cell recovery with diminished numbers of CD28neg CD8+ T cells (∼1/4th of that of relapse-free patients) preceded occurrence of malignant relapse. In multivariate analysis, lower CD28neg CD8+ T cell counts by day 60 postallograft were associated with a greater risk of subsequent relapse (hazard ratio [HR] 0.33; 95% confidence interval [CI]: 0.14-0.76; P = .01). Enumeration of CD28neg CD8+ T cells in patients could assist in predicting risk of relapse and help build an algorithm for accelerating the immune recovery by reducing the immunosuppressive treatment and considering the introduction of preemptive donor lymphocyte infusions

Etude de la voie PI3K/AKT dans les dysglobulinémie malignes (impact thérapeutique)

Le Myélome Multiple (MM) et la Maladie de Waldenström (MW) sont deux hémopathies lymphoïdes malignes caractérisées par l'envahissement de la moelle osseuse hématopoïétique par les cellules tumorales. Bien que la MW soit rare, le MM reste une des hémopathies les plus fréquentes, avec une incidence proche de 3 cas / 105 habitants. La médiane de survie dans le MM ne dépasse pas 5 ans et se situe aux alentours de 5 à 7 pour la MW. La voie PI3Kinase est une voie essentielle de survie, de croissance, régulant le cycle cellulaire et l'apoptose, de même que les phénome nes de migration et d'invasion des cellules tumorales. Cette voie de signalisation est constitutivement activée dans ces deux hémopathies et son inhibition entraine un effet cytotoxique sur les cellules tumorales et une induction de la mort cellulaire. Nous résumons dans ce travail l'état des connaissances sur cette voie dans les dysglobulinémies malignes et étudions son impact thérapeutique dans le MM et la MW.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Découverte d'une polyglobulie en médecine de ville (à propos d'une observation)

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Pollen record of sediment core MD99-2348

Palynology has been performed for the first time on Late Quaternary sediments of the Gulf of Lions. The aim is both to tighten the chronology of seismic profiles in the region, and to elucidate the vegetation of southern France during the Last Climatic Cycle. Four cores, taken on the shelf, mostly record Marine Isotope Stages (MIS) 1 and 2 and part of MIS 3 and MIS 5. The latter sediments might have been preserved in a paleodepression on the emergent shelf between the Rhône and the Hérault rivers. It would explain their preservation against transgression and regression erosions of more recent stages. This study also provides a synthesis of palynological continental data collected during the last 40 years in southern Europe. Preliminary comparisons made between the latter and new marine data demonstrate that refugia of Picea and Abies existed in southern France during MIS 3 and MIS 2. The dynamics of Artemisia, deciduous Quercus and Corylus, Abies and finally Fagus is also reconstructed for the last deglaciation. First results obtained in the Gulf of Lions confirm and complete that synthesis

Vegetation dynamics in southern France during the last 30 ky BP in the light of marine palynology

International audienceThe composition of the glacial vegetation of southern French plains has been a matter of debate for several decades. Vegetation is considered as steppic according to French and Spanish lacustrine pollen records whereas cave deposits suggest the presence of mesothermophilous trees through the Last Glacial Maximum. In our paper, we display new palynological records from marine sediments of the Gulf of Lions. They indicate the presence of Abies, Picea and deciduous Quercus in the Gulf of Lions, certainly located in the drainage basins of the Pyreneo-Languedocian rivers. These populations that were sensitive to short climatic events during Marine Isotopic Stage 2 could have been linked to northeastern Spanish and southeastern French relicts already evidenced by phylogenetic data. These trees were absent from the Rhone drainage basin during the deglaciation and certainly also disappeared from the Pyreneo- Languedocian drainage basins from ca 17 to 15 ky cal BP. Finally, the Last Glacial Maximum does not appear as stable, cold and dry as previously thought

Should isolated fetal ventriculomegaly measured below 12mm be viewed as a variant of the norm? Results of a 5-year experience in a prenatal referral center

International audienceBackground: Fetal ventriculomegaly (VM) is defined as lateral ventricles measured above 10mm. Some authors believe VM <12mm are variants of the norm and need not be addressed for referral ultrasound.Methods: A retrospective continuous cohort study of 127 confirmed fetal VM was divided into three groups after initial referral sonographic assessment: isolated VM <12mm (group A), isolated VM 12mm (group B), and VM associated with other malformations (group C). We reviewed obstetric outcome and neonate evolution after 1 month with the aim of defining a pertinent prenatal workup.Results: We reported fetal infections in all groups (p=.24) and chromosomal abnormalities only in group C (p=.41). Fetal magnetic resonance imaging (MRI) found initially undiagnosed brain abnormalities in groups B and C (12.5 and 14.1%, p<.05). Ratios of healthy children after 1 month stemming, respectively, from groups A, B, and C were 66.7, 62.5, and 20.2% (p<.05).Conclusions: Our results are in favor of a systematic referral ultrasound for every fetal VM, regardless of size, as soon as definition criterion is met. Additional paraclinical assessment (maternal serologic status for toxoplasmosis and cytomegalovirus, amniocentesis, fetal cerebral MRI) should be discussed depending on the situation

Active fault system across the oceanic lithosphere of the Mozambique Channel: Implications for the Nubia–Somalia southern plate boundary

International audienceSeismic reflection and multibeam echosounder data were acquired in the Mozambique Channel in 2014 and 2015 during the PTOLEMEE, PAMELA-MOZ02 and -MOZ04 marine surveys aboard the RV Atalante and Pourquoi Pas? These data revealed that an active fault system is deforming the oceanic lithosphere of the Mozambique Basin which has developed during Jurassic-Cretaceous times. The correlation between the fault system and the arrangement of earthquake epicenters suggests that this tectonically active zone directly connects northward with the southern part of the eastern branch of the East African Rift System which corresponds to the seismically active graben system bounding the northern part of the Davie ridge. The fault zone extends southwestward of the Mozambique Ridge along the same trend as the Agulhas-Falkland transform fault zone. The general organization of the fault zone shows the characteristics of an extensional system north of the Mozambique Channel (north of the Europa Island) and a right-lateral transtensional system with coeval normal faults and strike-slip faults south-west of Europa. This tectonic activity is associated with volcanic activity since at least Late Miocene times. Our findings emphasize that the eastern branch of East African Rift System is extending largely toward the south, not only in continental domains but also through the oceanic lithosphere of the Mozambique basin. This fault zone is participating to the complex plate boundary between the main African continent (Nubia Plate) and Madagascar (Somalia Plate)

Active Fault System across the Oceanic Lithosphere of the Mozambique Channel: Implications for the Southern Part of the East African Rift System

International audienceSeismic reflection and multibeam echosounder data acquired in the Mozambique Channel during the PAMELA project (PAssive Margin Exploration Laboratories, collaboration between IFREMER-TOTAL-IFPEN-CNRS-Univ. Brest, Rennes, Paris) revealed that an active fault system is deforming the oceanic lithosphere of the Mozambique Basin which has developed during Jurassic-Cretaceous times. The correlation between the fault system and the arrangement of earthquake epicenters suggests that this tectonically active zone directly connects northward with the southern part of the eastern branch of the East African Rift System which corresponds to the seismically active graben system bounding the northern part of the Davie ridge. The fault zone extends southwestward of the Mozambique Ridge along the same trend as the Agulhas-Falkland transform fault zone. The general organization of the fault zone shows the characteristics of an extensional system north of the Mozambique Channel (north of the Europa Island) and a right-lateral transtensional system with coeval normal faults and strike-slip faults south-west of Europa. This tectonic activity is associated with volcanic activity since at least Late Miocene times. Our findings emphasize that the eastern branch of East African Rift System is extending largely toward the south, not only in continental margin domains but also through the oceanic lithosphere of the Mozambique Basin. This fault zone is participating to the complex plate boundary between the main African continent (Nubia Plate) and the Somalia Plate