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

What factors are associated with recent intimate partner violence? findings from the WHO multi-country study on women's health and domestic violence

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence (IPV) against women is a global public health and human rights concern. Despite a growing body of research into risk factors for IPV, methodological differences limit the extent to which comparisons can be made between studies. We used data from ten countries included in the WHO Multi-country Study on Women's Health and Domestic Violence to identify factors that are consistently associated with abuse across sites, in order to inform the design of IPV prevention programs.</p> <p>Methods</p> <p>Standardised population-based household surveys were done between 2000 and 2003. One woman aged 15-49 years was randomly selected from each sampled household. Those who had ever had a male partner were asked about their experiences of physically and sexually violent acts. We performed multivariate logistic regression to identify predictors of physical and/or sexual partner violence within the past 12 months.</p> <p>Results</p> <p>Despite wide variations in the prevalence of IPV, many factors affected IPV risk similarly across sites. Secondary education, high SES, and formal marriage offered protection, while alcohol abuse, cohabitation, young age, attitudes supportive of wife beating, having outside sexual partners, experiencing childhood abuse, growing up with domestic violence, and experiencing or perpetrating other forms of violence in adulthood, increased the risk of IPV. The strength of the association was greatest when both the woman and her partner had the risk factor.</p> <p>Conclusions</p> <p>IPV prevention programs should increase focus on transforming gender norms and attitudes, addressing childhood abuse, and reducing harmful drinking. Development initiatives to improve access to education for girls and boys may also have an important role in violence prevention.</p

Breaking the Silence: Providing Authentic Opportunities for Parents to be Heard

Within Western society over the past 30 years a vivid picture has emerged of exactly what a ‘good parent’ looks like. This ideal parent works hard in order to contribute to the economic wellbeing of the nation at the same time as having abundant time for the nurture and educational development of their child. This parent does not question or challenge, but rather silently supports the superior knowledge of researchers, policy makers and educationalists. This parent is ‘valued’ as the child’s first educator, yet, we argue in this piece, has no voice. In this literature-based article we explore the silencing of parents within educational systems and look at the possibility of creating more authentic partnerships between them and educational settings. We challenge notions of parental conformity and instead encourage educational cultures where parents are invited to suggest and challenge, inspire and educate. We look at ways of opening positive channels of communication between parents and educationalists, where knowledge and perceptions of quality can be genuinely shared, recognising and respecting the multiple dimensions of school and family life

Socioeconomic disparities in mortality after diffuse large B-cell lymphoma in the modern treatment era.

Despite advances in treatment, including the introduction of rituximab, survival after diffuse large B-cell lymphoma (DLBCL) remains heterogeneous. However, no studies have considered the association between neighborhood socioeconomic status (SES) and race/ethnicity on DLBCL mortality before (1988-2000) and after (2001-2009) the introduction of rituximab. We studied all 33,032 DLBCL patients diagnosed between 1988-2009 in California for vital status through December 31, 2010. Patients diagnosed from 2001 to 2009 vs 1988 to 2000 had significantly decreased overall and DLBCL-specific mortality. However, those living in lower SES neighborhoods had 34% (95% confidence interval [CI], 27%-40%) and 24% (95% CI, 16%-32%) higher mortality rate from all causes and lymphoma, respectively, than patients in higher SES neighborhoods. The magnitude of mortality disparities by neighborhood SES was more marked in younger (&lt;65 years) than in older patients (≥65 years), in married than nonmarried patients, and after 2000. We concluded that patients living in low SES neighborhoods had substantially worse survival after DLBCL, and this disparity was striking in younger (ie, not eligible for Medicare-aged) patients, married patients, and after the introduction of rituximab. These disparities suggest there are barriers, including inadequate insurance coverage with additional financial burden, to effective treatment among socioeconomically disadvantaged patients