AUGMENT : a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma

PURPOSE Patients with indolent non-Hodgkin lymphoma typically respond well to first-line immunochemotherapy. At relapse, single-agent rituximab is commonly administered. Data suggest the immunomodulatory agent lenalidomide could increase the activity of rituximab. METHODS A phase III, multicenter, randomized trial of lenalidomide plus rituximab versus placebo plus rituximab was conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Patients received lenalidomide or placebo for 12 cycles plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5. The primary end point was progression-free survival per independent radiology review. RESULTS A total of 358 patients were randomly assigned to lenalidomide plus rituximab (n = 178) or placebo plus rituximab (n = 180). Infections (63% v 49%), neutropenia (58% v 23%), and cutaneous reactions (32% v 12%) were more common with lenalidomide plus rituximab. Grade 3 or 4 neutropenia (50% v 13%) and leukopenia (7% v 2%) were higher with lenalidomide plus rituximab; no other grade 3 or 4 adverse event differed by 5% or more between groups. Progression-free survival was significantly improved for lenalidomide plus rituximab versus placebo plus rituximab, with a hazard ratio of 0.46 (95% CI, 0.34 to 0.62; P < .001) and median duration of 39.4 months (95% CI, 22.9 months to not reached) versus 14.1 months (95% CI, 11.4 to 16.7 months), respectively. CONCLUSION Lenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile

Textural characteristics and facies of sand-rich contourite depositional systems

Brackenridge, Rachel E. ... et al.-- 30 pages, 14 figures, 2 tablesThis work presents a detailed study of CONTOURIBER and Integrated Ocean Drilling Program 339 sediment data targeting sand‐rich contourites in the Eastern Gulf of Cadiz. All of the collected sediments are interpreted as contourites (deposited or reworked by bottom currents) on the basis of oceanographic setting, seismic and morphometric features, and facies characteristics. A variety of sandy and associated facies are found across the study area including: (i) bioturbated muddy contourites; (ii) mottled silty contourites; (iii) very fine mottled and fine‐grained bioturbated sandy contourites; (iv) massive and laminated sandy contourites; and (v) coarse sandy/gravel contourites. The thickest sands occur within contourite channels and there is a marked reduction in sand content laterally away from channels. Complementary to the facies descriptions, grain‐size analysis of 675 samples reveals distinctive trends in textural properties linked to depositional processes under the action of bottom currents. The finest muddy contourites (200 μm) are better sorted. They result from the action of dominant bedload transport and winnowing at high current speeds. The results highlight the importance of bottom current velocity, sediment supply and bioturbational mixing in controlling contourite facies. Despite growing interest in their hydrocarbon exploration potential, contourite sands have remained poorly understood. This research therefore has important implications for developing current understanding of these deposits and aiding the correct interpretation of deep marine sands and depositional processesThis research formed part of the lead author's PhD programme at Heriot‐Watt University, supported by an Ali Danesh Scholarship and of the Masters by research from Claudia Jones in the Department of Earth Sciences of the Royal Holloway University of London. The research was also partially supported through the Spanish Ciencia y Tecnologías Marinas projects CTM 2012‐39599‐C03, CGL2016‐80445‐R, and CTM2016‐75129‐C3‐1‐R, and conducted in the framework of ‘The Drifters’ Research Group of the Royal Holloway University of London (RHUL)Peer Reviewe

Phytoplankton production in the Tagus estuary (Portugal)

Biomass and phytoplankton photosynthetic response were studied in the lower Tagus estuary weekly, and related to environmental conditions in February, March and April 1994. The Photosynthesis-Irradiance ((P-I)-I-B) relation was studied based on the light-saturated photosynthesis rate (P(B)m) and the light-limited initial slope (a(B)). The nutrient concentrations observed were high enough to be considered as not limiting phytoplankton growth. Tagus estuary phytoplankton seems, to a certain extent, adapted to high turbid conditions, being able to utilize the low light levels more efficiently, which was translated by high values of a(B) [0.10-0.20 mg C (mg Chl a)(-1) h(-1) (W m(-2))(-1)]; however, light seems to limit phytoplankton production in the water column.Une étude de la biomasse et de la réponse photosynthétique du phytoplancton en fonction des facteurs environnementaux a été menée dans l'estuaire du Tage, de février à avril 1994, (prélèvements hebdomadaires). La relation photosynthèse-éclairement (P−BI) a étéétudiée sur la capacité photosynthétique en lumière saturante (PBm) et le rendement photosynthétique en lumière limitante (aB). La concentration de sels nutritifs, pendant les mois étudiés, a été suffisamment élevée pour être considérée comme non limitante pour la croissance du phytoplancton. Le phytoplancton de l'estuaire du Tage semble, par sa photosynthèse, bien adaptéà des conditions de haute turbidité; les cellules augmentent le rendement d'utilisation des bas niveaux d'éclairement, ce qui se traduit par les hautes valeurs de aB [0,10–0,20 mg C (mg Chla)−1 h−1 (W m−2)−1] bien que l'éclairement semble être le facteur limitant de la production phytoplanctonique sur la colonne d'eau

Behaviour of organic carbon in nine contrasting European estuaries

A cross-system comparison of organic carbon origin and behaviour in nine European estuaries is presented. The study sites display a very large range of hydrological and environmental conditions. The watershed of the respective estuaries were characterized by plotting the total organic carbon (TOC) in the rivers versus the inhabitants/discharge ratio, This allows to distinguish four types of watershed with regard to anthropogenic forcing and organic carbon levels: polluted by sewage inputs (Scheldt and to a much lesser extent, Ems, Sado and Thames), decontaminated (Elbe and Rhine), pristine (Gironde and Douro) and eutrophized (Loire and Scheldt). In the estuarine zone, dissolved organic carbon (DOC) almost always decreased linearly with increasing salinity. Exceptions were: the Scheldt, where a net consumption of sewage-derived DOC was observed, the Gironde, where a net production of DOC occurred in the maximum turbidity zone (MTZ) and the Sado and Ems, where DOC was supplied from large intertidal areas. By contrast, a large fraction of the riverine particulate organic carbon (POC) was mineralized in all the estuaries, except the Douro, where residence time of waters is only a few days. A fraction of POC appeared however refractory and accumulated in the MTZs, where terrestrial soil-derived material dominates (Elbe, Ems, Loire, Gironde and Sado). In the marine regions of most estuaries, autochthonous POC was present during spring and summer. The analysis of all river and estuarine data allows estimation of the loss of continental POC occurring in each estuary. It decreases in the following order: Scheldt much greater than Thames > Ems = Sado = Loire > Gironde > Elbe > Rhine > Douro, which almost corresponds to the anthropogenic pressure in the respective watersheds. Two major variables appear to control the intensity of this mineralization: the origin of the POC, the lability increasing with pollution, and the residence time of particles in the estuarine zone

Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward - report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology

Mature T-cell and T/NK-cell neoplasms are both uncommon and heterogeneous, among the broad category of non-Hodgkin lymphomas. Owing to the lack of specific genetic alterations in the vast majority, most currently defined entities show overlapping morphological and immunophenotypic features, and therefore pose a challenge to the diagnostic pathologist. In the light of recent immunophenotypic, cytogenetic and molecular genetics advances in the field of T-cell and T/NK-cell lymphomas, the focus of the lymphoma workshop of the European Association for Haematopathology/Society for Hematopathology meeting in Lisbon, Portugal, in October 2012 was to refine existing diagnostic criteria and clarify the borders between overlapping entities. The panel reviewed over 200 submitted cases, which were grouped into five categories: (i) angioimmunoblastic T-cell lymphoma and T-follicular-helper-cell-associated lymphomas; (ii) CD30-positive T-cell lymphomas/lymphoproliferative diseases; (iii) extranodal T-cell and NK-cell neoplasms; (iv) EBV-associated T-cell/NK-cell lymphomas/lymphoproliferative diseases; and (v) peripheral T-cell lymphoma, not otherwise specified, post-transplant lymphoproliferative disorders, and mimics. This report summarizes the discussions and conclusions of the workshop, which question current diagnostic criteria and provide recommendations for refining existing classifications

Prospective subgroup analyses of the randomized MCL-002 (SPRINT) study : lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma

International audienceIn the mantle cell lymphoma (MCL)-002 study, lenalidomide demonstrated significantly improved median progression-free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long-term follow-up data and results of preplanned subgroup exploratory analyses from MCL-002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL-002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1-21; 28-day cycles) or single-agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine). The intent-to-treat population comprised 254 patients (lenalidomide, n = 170; IC, n = 84). Subgroup analyses of PFS favoured lenalidomide over IC across most characteristics, including risk factors, such as high MCL International Prognostic Index score, age ≥65 years, high lactate dehydrogenase (LDH), stage III/IV disease, high tumour burden, and refractoriness to last prior therapy. By multivariate Cox regression analysis, factors associated with significantly longer PFS (other than lenalidomide treatment) included normal LDH levels (P < 0·001), nonbulky disease (P = 0·045), <3 prior antilymphoma treatments (P = 0·005), and ≥6 months since last prior treatment (P = 0·032). Overall, lenalidomide improved PFS versus single-agent IC therapy in patients with relapsed/refractory MCL, irrespective of many demographic factors, disease characteristics and prior treatment history