39 research outputs found
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
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Testing the Surge: Why Did Violence Decline in Iraq in 2007?
Why did violence decline in Iraq in 2007? Many policymakers and scholars credit the “surge,” or the program of U.S. reinforcements and doctrinal changes that began in January 2007. Others cite the voluntary insurgent stand-downs of the Sunni Awakening or say that the violence had simply run its course with the end of a wave of sectarian cleansing; still others credit an interaction between the surge and the Awakening. The difference matters for policy and scholarship, yet this debate has not moved from hypothesis to test. An assessment of the competing claims based on recently declassified data on violence at local levels and information gathered from seventy structured interviews with coalition participants finds little support for the cleansing or Awakening theses. Instead, a synergistic interaction between the surge and the Awakening was required for violence to drop as quickly and widely as it did: both were necessary; neither was sufficient. U.S. policy thus played an important role in reducing the violence in Iraq in 2007, but Iraq provides no evidence that similar methods will produce similar results elsewhere without local equivalents of the Sunni Awakening