First report of an Ediacarian basement in the Western Alps: the Serre Chevalier crystalline unit (Briançonnais domain, France)

We report new LA-ICP-MS U-Pb zircon ages of varied crystalline rocks occurring in the Serre Chevalier crystalline terrain, an allochtonous basement unit located at the top of the Briançonnais nappes stack ∼5 km west of Briançon city. Mapped as an undifferentiated metasedimentary basement on the geological map at 1/50,000 scale, this unit actually displays varied lithologies including alternating micaschist, paragneiss, quartzite, coarse-grained conglomerate and felsic (leptynite) to mafic (amphibolite) gneiss of magmatic origin. All rocks were metamorphosed in response to a dominant pre-Alpine event under amphibolite facies conditions. Partial recrystallization under low-grade amphibolite to greenschist facies conditions was associated with alpine events. Zircon ages were obtained on four types of rocks: (i) a micaceous quartzite from the core of the metasedimentary unit displays a dominant age population around 610 Ma, with a minimal age of 580 Ma, and subordinated age populations at c. 940 Ma, 1825 Ma and 2100-2560 Ma ; (ii) a granite boulder from a coarse-grained conglomerate yields a well-defined age of 582 ± 5 Ma and subordinated inherited ages between 1800 and 2200 Ma. Zircon rims of probable metamorphic origin provide a concordant age of 492 ± 4 Ma ; (iii) a gneissic band in the vicinity of the conglomerate is dated at 597 ± 4 Ma ; (iv) a coarse-grained garnet amphibolite yields an age of 517 ± 3 Ma interpreted as the emplacement age of the protolith, either as intrusive unit cutting accross the sedimentary succession or lava intercalated within the sediments. The mainly Ediacarian record in the metasediments (quartzite and granite boulder in conglomerate) lead us to conclude that this material resulted from the erosion of a nearby Ediacarian (Cadomian ?) basement. The age of 517 Ma obtained on the amphibolite provides a minimum age for the sedimentary succession which deposition is therefore bracketed between 582 Ma and 517 Ma. This interval is comparable to that of the metasedimentary units of the Brioverian group of the Armorican Massif. Based on their low Th/U ratio, the 492 Ma-old zircon rims in the granite boulder are attributed to an Upper Cambrian metamorphic event

First report of an Ediacarian basement in the Western Alps: the Serre Chevalier crystalline unit (Briançonnais domain, France)

We report new LA-ICP-MS U-Pb zircon ages of varied crystalline rocks occurring in an allochtonous unit of basement terrain located at the top of the Briançonnais nappes stack ~5 km west of Briançon city. Mapped as an undifferentiated metasedimentary basement on the geological map at 1/50,000 scale, this unit actually displays varied lithologies including alternating micaschist, paragneiss, quartzite, coarse-grained conglomerate and felsic (leptynite) to mafic (amphibolite) gneiss of magmatic origin. All rocks were metamorphosed in response to a dominant pre-Alpine event under garnet-amphibolite facies conditions. Retrogression under amphibolite to greenschits facies was associated with alpine events. Zircon ages were obtained on four types of rocks: (i) a micaceous quartzite from the core of the metasedimentary unit displays a dominant age population around 610 Ma and subordinated age populations at c. 940 Ma, 1825 Ma and 2100-2560 Ma ; (ii) a granite boulder from a coarse-grained conglomerate yields a dominant magmatic age of 582 ± 5 Ma and subordinated inherited ages between 1800 and 2200 Ma. Zircon metamorphic rims provide a concordant age of 492 ± 4 Ma ; (iii) a gneissic band in the vicinity of the conglomerate is dated at 597 ± 4 Ma ; (iv) a coarse-grained garnet amphibolite yields an age of 517 ± 3 Ma interpreted as the emplacement age of the protolith. The mainly Ediacarian record in the metasediments (quartzite and granite boulder in conglomerate) with no evidence of younger zircons indicates that this material resulted from the erosion of a nearby Ediacarian (Cadomian ?) basement. The age of 517 Ma obtained on the amphibolite provide a minimum age for the sedimentary succession which deposition is therefore bracketed between 582 Ma and 517 Ma. This interval is comparable to that of the metasedimentary units of the Brioverian group of the Armorican Massif. Based on their low Th/U ratio, the 492 Ma-old zircon rims in the granite boulder are attributed to an Upper Cambrian metamorphic event, but it is not yet clear whether this event corresponds to the garnet - amphibolite facies metamorphism recorded in the Serre Chevalier crystalline terrain

Notice explicative de la feuille Les Herbiers à 1/50000, n°537

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BCL2 expression in CD105 positive neoangiogenic cells and tumor progression in angioimmunoblastic T-cell lymphoma.

International audienceThe angiogenic microenvironment has been known to be a component of angioimmunoblastic T-cell lymphoma since its initial characterization. We have shown that angioimmunoblastic T-cell lymphoma endothelial cells produce vascular endothelial growth factor-A (VEGFA), and participate in lymphoma progression. In squamous cell carcinoma, endothelial BCL2 expression induces a crosstalk with tumor cells through VEGFA, a major mediator of tumoral angiogenesis. In the present study, we analyzed BCL2 and VEGFA in 30 angioimmunoblastic T-cell lymphomas, using triple immunofluorescence to identify protein coexpression in well-characterized lymphoma cells and microenvironment neoangiogenic endothelial cells. Using quantitative real-time PCR, we assessed mRNA expression levels in laser-microdissected endothelial and lymphoma cells. In lymphoma cells, as in endothelial cells, BCL2 and VEGFA proteins were coexpressed. BCL2 was expressed only in neoangiogenic CD34(+)CD105(+) endothelial cells. In laser-microdissected cells, mRNA studies showed a significant relationship between BCL2 and VEGFA levels in CD34(+) endothelial cells, but not in CD3(+)CD10(+)lymphoma cells, or in CD34(+) endothelial cells from lymph node hyperplasia. Further study showed that, in AITL, BCL2 mRNA levels in CD34(+)CD105(+) neoangiogenic endothelial cells also correlated with microvessel density, International Prognostic Index, Ann Arbor stage, bone marrow involvement and elevated LDH. BCL2 expression by CD105(+) neoangiogenic endothelial cells is related to tumor progression in angioimmunoblastic T-cell lymphoma

Relapsed diffuse large B-cell lymphoma present different genomic profiles between early and late relapses

International audienc

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Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial

Background The outcome of diff use large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18–59 years, the potential survival benefi t provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. Methods We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclo phosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18–59 years with untreated diff use large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of effi cacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. Findings One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75–86) in the R-ACVBP group and 67% (59–73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38–0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81–91] vs 73% [66–79]; HR 0·48 [0·30–0·76]; p=0·0015) and overall survival (92% [87–95] vs 84% [77–89]; HR 0·44 [0·28–0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3–4 haematological toxic eff ects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]). Interpretation Compared with standard R-CHOP, inten sifi ed immunochemotherapy with R-ACVBP signifi cantly improves survival of patients aged 18–59 years with diff use large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic eff ects of the intensive regimen were raised but manageable. Funding Groupe d’Etudes des Lymphomes de l’Adulte and Amgen

Lymphoma In Patients With Inflammatory Bowel Disease: A Multicenter Collaborative Study Between Getaid And Lysa.

International audienceAbstract Background IBD is associated with an increased risk of developing lymphoma. Although recent data clarifies lymphoma epidemiology in IBD patients, clinical and pathological characteristics of lymphoma occurring in IBD remain ill-known. Methods Patients with IBD and lymphoma were retrospectively identified in the framework of a national collaborative study including the Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID) and the Lymphoma Study Association (LYSA). We characterized clinical and prognostic features for the 3 most frequent lymphoma subtypes occurring in IBD. We performed a multicentric case-control study. Controls (lymphoma de novo) were matched (5:1) to cases on gender, age at diagnosis, lymphoma subtype, year of diagnosis, IPI/FLIPI indexes. Overall survival (OS) and progression free survival were compared between cases and controls. Results 133 IBD patients with lymphoma were included (males = 62.4 %, median age at lymphoma diagnosis = 49 years in males ; 42 in females). Most had Crohn’s disease (73.7 %) and were exposed to thiopurines (59.4 %). The most frequent lymphoma subtypes were diffuse large B cell lymphoma (DLBCL, 45.1 %), Hodgkin lymphoma (HL, 18.8 %), and follicular lymphoma (FL, 10.5 %). When matched with 365 controls, prognosis was improved in IBD patients with DLBCL compared to controls (p = 0.0064, hazard ratio = 0.36) or similar (HL and FL). Conclusion Lymphomas occurring in IBD patients do not seem to have a worse outcome than in patients without IBD. Due to the scarcity of this situation, those patients should be managed in expert centers

Determinants of outcome in Covid-19 hospitalized patients with lymphoma: A retrospective multicentric cohort study

International audienceBackgroundPatients with lymphoma are immunocompromised because of the disease per se and its treatments. We aimed to describe the characteristics of patients with lymphoma hospitalized for Coronavirus Disease 2019 (Covid-19) and to analyze pre-Covid-19 determinants of mortality.MethodsThis retrospective multicentric cohort study used the Programme de Médicalisation des Systèmes d'Information database to identify all adult patients with lymphoma, hospitalized for Covid-19 in March and April 2020, in 12 hospitals of three French regions with pandemic outbreaks. The characteristics of lymphoma and Covid-19 were collected from medical charts.FindingsEighty-nine patients were included. The median age was 67 years (range, 19–92), 66% were male and 72% had a comorbidity. Most patients had B-cell non-Hodgkin lymphoma (86%) and had received a lymphoma treatment within one year (70%). With a median follow-up of 33 days from admission, 30-day overall survival was 71%, (95% confidence interval, 62–81%). In multivariable analysis, having an age ≥ 70 years (hazard ratio 2·87, 1·20–6·85, p = 0·02) and relapsed/refractory lymphoma (hazard ratio 2·54, 1·14–5·66, p = 0·02) were associated with mortality. Recent bendamustine treatment (n = 9) was also pejorative (hazard ratio 3·20, 1·33–7·72, p = 0·01), but was strongly associated with relapsed/refractory lymphoma. Remarkably, 30-day overall survival for patients < 70 years of age without relapsed/refractory lymphoma was 88% (78% - 99%).InterpretationThirty-day mortality was associated with being older and relapsed/refractory lymphoma. Survival of patients younger than 70 years without relapsed/refractory lymphoma was comparable to that of the general population

Prolonged in-hospital stay and higher mortality after Covid-19 among patients with non-Hodgkin lymphoma treated with B-cell depleting immunotherapy

International audienceProlonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow-up of 191 days (3–260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population