Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study

Background: Relapsed or refractory diffuse large B-cell and mantle-cell lymphoma have a poor prognosis. The EPOCH regimen and rituximab monotherapy have demonstrated activity as salvage therapies. Because of their non-overlapping toxicity, we evaluated their combination as salvage therapy in a phase II study. Patients and methods: Patients with relapsed or refractory CD20-positive large B-cell and mantle-cell lymphoma were offered treatment with rituximab 375 mg/m2 intravenously (i.v.) on day 1, doxorubicin 15 mg/m2 as a continuous i.v. infusion on days 2-4, etoposide 65 mg/m2 as a continuous i.v. infusion on days 2-4, vincristine 0.5 mg as a continuous i.v. infusion on days 2-4, cyclophosphamide 750 mg/m2 i.v. on day 5 and prednisone 60 mg/m2 orally on days 1-14. Results: Fifty patients, with a median age of 56 years (range 23-72), entered the study. Twenty-five had primary diffuse large B-cell lymphoma, 18 transformed large B-cell lymphoma and seven mantle-cell lymphoma. The median number of prior chemotherapy regimens was 1.7 (range one to four). The median number of treatment cycles was four (range one to six). Possible treatment-related death occurred in two patients. Objective responses were obtained in 68% of patients (28% complete responses, 40% partial responses). Nineteen patients received consolidating high-dose chemotherapy with autologous stem-cell transplantation. The median follow-up was 33 months. Three patients developed a secondary myelodysplastic syndrome. The median overall survival was 17.9 months; the projected overall survival at 1, 2 and 3 years was 66, 42 and 35%, respectively. The median event-free survival was 11.8 months; the projected event-free survival at 1, 2 and 3 years was 50, 30 and 26%, respectively. Conclusion: The rituximab-EPOCH regimen is effective and well tolerated, even in extensively pretreated patients with relapsed or refractory large B-cell lymphoma and mantle-cell lymphom

Can gold be used as a hedge against the risks of Sharia-compliant securities? Application for Islamic portfolio management

In this paper, we investigate whether gold hedges Sharia-compliant stocks and Sukuk during the period from September 2005 to October 2017. The inference is taken by using both the DCC-GARCH model and the wavelet coherence analysis. On the whole, our finding suggests that gold is not effective in hedging the fluctuations of Sharia-compliant securities. However, we find that combining gold with stocks (and Sukuk) is useful in diversification and portfolio optimization. These results imply that, while gold is an excellent hedge for plain vanilla securities, it is not for Islamic exposures. This is important in light of the increasing amount of assets that are managed according to Islamic screening

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes

Multiphase Phanerozoic Subsidence and Uplift History Recorded in the Congo Basin: A Complex Successor Basin

International audienceThe Congo Basin of central Africa is a large iconic Phanerozoic sedimentary basin whose origin and tectonic evolution are poorly understood, mostly because of a lack of modern stratigraphic data, reflecting a long hiatus in field investigations during the past five decades. It is usually assumed that the Congo Basin experienced a long and continuous history of slow subsidence since the late Precambrian (e.g. 2–4 m/Ma), linked to steady-state mantle processes. Here, we used revised sedimentological and stratigraphic data of the four historic deep boreholes drilled in the center of the basin to calculate a new first-order model for its subsidence and uplift history. Because the sedimentary sequences of this basin are largely terrestrial, we apply a new backstripping method especially designed for continental domain. The results reveal two main episodes of subsidence: initially rapid subsidence during the Carboniferous-Triassic (10–20 m/Ma), and then slower subsidence during the Jurassic-Cretaceous (5–10 m/Ma), punctuated by several uplifts at 160–180 Ma (e.g. ‘Karoo’), 120–140 Ma (e.g. ‘Paraná-Etendeka’), and again in the Cenozoic, ca. 30–50 Ma (e.g. ‘Ethiopian’). This complex, multiphase subsidence and uplift history of the Congo Basin can be linked to evolving far-field geodynamic processes that first led the formation of Pangea (large-scale compression) during the late Paleozoic, and then to its break-up associated with successive outpourings of Large Igneous Provinces (or hotspot plumes) and the opening of the Indian and South Atlantic Oceans around Africa