Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

Background: chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. Methods: we randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. Results: the median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Conclusions: ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.)

CARACTERIZACIÓN GEOQUÍMICA DE MINERALES PESADOS RECOLECTADOS EN LA ZONA NOR-OCCIDENTAL DEL ESTADO BOLÍVAR / GEOCHEMICAL AND MINERALOGICAL STUDY OF HEAVY MINERAL IN THE NORTH-WEST AREA OF BOLIVAR STATE

Para la caracterizaci&oacute;n geoqu&iacute;mica de minerales pesados se analizaron 47 muestras recolectadas en las cuencas de losr&iacute;os Aro, Pao, Cuchivero, Guaniamo, Suapure, Parguaza y Cataniapo, localizadas en la zona nor-occidental del estadoBol&iacute;var, con el fin de ubicar y limitar zonas de inter&eacute;s para la prospecci&oacute;n minera. El an&aacute;lisis qu&iacute;mico se realiz&oacute; mediantela t&eacute;cnica de Espectrometr&iacute;a de Emisi&oacute;n &Oacute;ptica con Plasma Inductivamente Acoplado, para los &oacute;xidos mayoritarios yminoritarios (SiO2, Al2O3, Fe2O3, MgO, CaO, Na2O, K2O, TiO2, P2O5, MnO) y por Espectrometr&iacute;a de Masa con PlasmaInductivamente Acoplado para las traza (Y, Zr, Nb, Hf, La, Ce, Nd, Th, U, Cr). El tratamiento estad&iacute;stico aplicado fue elAn&aacute;lisis Exploratorio de Datos (AED). Con la informaci&oacute;n obtenida se generaron los mapas geoqu&iacute;micos de distribuci&oacute;nde concentraciones, situando las anomal&iacute;as. El an&aacute;lisis mineral&oacute;gico se efectu&oacute; por medio de la t&eacute;cnica de Difracci&oacute;n deRayos X (DRX), para las muestras que resultaron an&oacute;malas. Los resultados permitieron dividir el &aacute;rea de estudio en cuatrozonas an&oacute;malas. La Zona A present&oacute; valores an&oacute;malos en los elementos y &oacute;xido Cr, Y, La, Ce, Nd, Th, U, P2O5 y altasconcentraciones de Fe2O3 y TiO2, y el an&aacute;lisis mineral&oacute;gico arroj&oacute; como posibles fases minerales: ilmenita, magnetita,cromita, hematita e ilmenorutilo. La Zona B con anomal&iacute;as en Zr, Hf, y U y altas concentraciones de Nb, TiO2 y Fe2O3,las fases minerales propuestas son ilmenita y circ&oacute;n. La Zona BI con anomal&iacute;as en MnO, como fases minerales sepresentaron: ilmenita rica en Mn, hematita y magnetita y la Zona BII con anomal&iacute;as en Y, La, Ce, Nd, Th, U, P2O5 y altasconcentraciones de Zr, Hf, Nb TiO2 y Fe2O3; las fases minerales identificadas en esta zona son monacita, ilmenita rica enMn e ilmenita.ABSTRACTThis paper presents a geochemical and mineralogical study of heavy minerals collected in the north-west Bolivar state riverbasins (Aro, Pao, Cuchivero, Guaniamo, Suapure, Parguaza y Cataniapo) in order to locate and delimit areas of interestfor mining exploration. Chemical analysis were performed by using the Inductively Coupled Plasma Optical EmissionSpectrometry (ICP-OES) technique for major and minor elements (SiO2, Al2O3, Fe2O3, MgO, CaO, Na2O, K2O, TiO2, P2O5,MnO) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) technique for trace elements (Y, Zr, Nb, Hf, La,Ce, Nd, Th, U, Cr). The statistical treatment applied was Exploratory Data Analysis (EDA). The results obtained allowedgenerating the geochemical maps and locating the anomalies. Mineralogical analysis was performed by using the X-RayDiffraction (XRD) technique for the anomalous samples. The results allowed dividing the study area into four anomalouszones. Zone A had anomalous values in the elements Cr, Y, La, Ce, Nd, Th, U, P2O5 and high concentrations in Fe2O3 andTiO2 whereas mineralogical analysis showed as potential mineral phases: ilmenite, magnetite, chromite, hematite andilmenorutile. Zone B with anomalies in Zr, Hf, and U and high concentrations of Nb, TiO2 and Fe2O3 with suggested phaseminerals: ilmenite and zircon. Zone BI with anomalies in MnO, and the mineral phases presented were Mn-rich ilmenite,hematite and magnetite. Finally Zone BII with anomalous values in Y, La, Ce, Nd, Th, U, P2O5 and high concentrations ofZr, Hf, Nb TiO2 y Fe2O3; the mineral phases identified in this zone were monacite, Mn-rich ilmenite and ilmenite.Keywords: Geochemistry, Exploration, Heavy minerals, Anomalies, Geochemical maps