Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Short-Term Environmental Enrichment Rescues Adult Neurogenesis and Memory Deficits in APPSw,Ind Transgenic Mice

Epidemiological studies indicate that intellectual activity prevents or delays the onset of Alzheimer's disease (AD). Similarly, cognitive stimulation using environmental enrichment (EE), which increases adult neurogenesis and functional integration of newborn neurons into neural circuits of the hippocampus, protects against memory decline in transgenic mouse models of AD, but the mechanisms involved are poorly understood. To study the therapeutic benefits of cognitive stimulation in AD we examined the effects of EE in hippocampal neurogenesis and memory in a transgenic mouse model of AD expressing the human mutant β-amyloid (Aβ) precursor protein (APPSw,Ind). By using molecular markers of new generated neurons (bromodeoxiuridine, NeuN and doublecortin), we found reduced neurogenesis and decreased dendritic length and projections of doublecortin-expressing cells of the dentate gyrus in young APPSw,Ind transgenic mice. Moreover, we detected a lower number of mature neurons (NeuN positive) in the granular cell layer and a reduced volume of the dentate gyrus that could be due to a sustained decrease in the incorporation of new generated neurons. We found that short-term EE for 7 weeks efficiently ameliorates early hippocampal-dependent spatial learning and memory deficits in APPSw,Ind transgenic mice. The cognitive benefits of enrichment in APPSw,Ind transgenic mice were associated with increased number, dendritic length and projections to the CA3 region of the most mature adult newborn neurons. By contrast, Aβ levels and the total number of neurons in the dentate gyrus were unchanged by EE in APPSw,Ind mice. These results suggest that promoting the survival and maturation of adult generated newborn neurons in the hippocampus may contribute to cognitive benefits in AD mouse models

Chromosome and abnormalities are associated with an even worse outcome and karyotype complexity in patiens with chronic lymphocytic leukemia and TP53 A

TP53 aberrations (deletions and/or mutations, TP53ab) in chronic lymphocytic leukemia (CLL) are associated with dismal clinical outcome and reduced life expectancy. However, mounting evidence suggests that within cases carrying TP53ab other cytogenetic features may also influence the clinical outcome. Alterations in chromosome 8, in particular 8p losses (affecting several regions, from 8p12 to 8p23) and 8q gains (usually involving 8q24, where MYC is located), are enriched in TP53ab patients and have been proposed as features with potential prognostic value within this aggressive group.Ye

Brazilian version of the Mattis dementia rating scale: diagnosis of mild dementia in Alzheimer's disease Versão brasileira da escala de avaliação de demência de Mattis: diagnóstico de demência leve na doença de Alzheimer

OBJECTIVES: To verify the diagnostic accuracy of the Brazilian version of the Mattis Dementia Rating Scale (DRS) in the diagnosis of patients with mild dementia in Alzheimer's disease (AD); to verify the interference of the variables age and schooling on the performance of the DRS. METHOD: The DRS was administered to 41 patients with mild AD and to 60 controls. In order to analyze the effects of age and schooling on the performance of the tests, patients and controls were separated into three age groups and three levels of schooling. RESULTS: The cutoff score of 122 showed a sensitivity of 91.7 % and specificity of 87.8 %. Age and schooling interfered in the DRS total score and in the scores of its subscales. CONCLUSION: The DRS showed good diagnostic accuracy in the discrimination of patients with mild AD from the control individuals. In the sample examined, the effects of schooling were more marked than age.<br>OBJETIVO: Verificar a acurácia diagnóstica da versão brasileira da Escala de Avaliação de Demência (DRS) no diagnóstico de pacientes com doença de Alzheimer (DA) leve; verificar a interferência das variáveis idade e escolaridade no desempenho da DRS. MÉTODO: A DRS foi aplicada em 41 pacientes com DA provável, de intensidade leve, e em 60 controles. Para análise das variáveis idade e escolaridade, pacientes e controles foram divididos em três grupos de idade e em três níveis de escolaridade. RESULTADOS: A nota de corte 122 demonstrou sensibilidade de 91,7% e especificidade de 87,8%. Idade e escolaridade interferiram no escore total e nos escores das subescalas da DRS. CONCLUSÃO: A DRS demonstrou boa acurácia diagnóstica na discriminação entre pacientes com DA leve e indivíduos controles. Na população estudada, os efeitos da escolaridade foram mais acentuados que os da idade

Does partial root-zone drying improve irrigation water productivity in the field? A meta-analysis

Partial root-zone drying improves irrigation water productivity (IWP, yield per unit applied irrigation water) with respect to controls receiving substantially more water, but similar gains are often achieved with conventional deficit irrigation. This paper presents a meta-analysis of IWP for a broad range of horticultural crops and environments. Two comparisons were preformed: (a) crops managed with either partial root-zone drying or conventional deficit irrigation against controls receiving substantially more water than the two water-saving techniques, (b) crops managed with partial root-zone drying and their counterparts with conventional irrigation where both received similar amounts of irrigation. In relation to controls receiving substantially more water, conventional deficit irrigation increased IWP by an average 76% and partial root-zone drying by 82%; the gains from both water-saving methods were statistically undistinguishable. Yield per unit applied irrigation water of crops under partial root-zone drying was significantly (P = 0.007) but modestly (5%) higher than in their counterparts with conventional irrigation where both received similar amounts of irrigation. In 80% of cases the difference in IWP between the two methods was in the ±20% range. Considering the cost and management complexity of implementing partial root-zone drying, it is critical to identify the rare conditions where this method could be economically justified.V. O. Sadra