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

The Tumor Microenvironment: The Making of a Paradigm

What has been will be again, what has been done will be done again; there is nothing new under the su

Quantification of ocean heat uptake from changes in atmospheric O2 and CO2 composition

The ocean is the main source of thermal inertia in the climate system. Ocean heat uptake during recent decades has been quantified using ocean temperature measurements. However, these estimates all use the same imperfect ocean dataset and share additional uncertainty due to sparse coverage, especially before 2007. Here, we provide an independent estimate by using measurements of atmospheric oxygen (O2) and carbon dioxide (CO2) – levels of which increase as the ocean warms and releases gases – as a whole ocean thermometer. We show that the ocean gained 1.29 ± 0.79 × 1022 Joules of heat per year between 1991 and 2016, equivalent to a planetary energy imbalance of 0.80 ± 0.49 W watts per square metre of Earth’s surface. We also find that the ocean-warming effect that led to the outgassing of O2 and CO2 can be isolated from the direct effects of anthropogenic emissions and CO2 sinks. Our result – which relies on high-precision O2 atmospheric measurements dating back to 1991 – leverages an integrative Earth system approach and provides much needed independent confirmation of heat uptake estimated from ocean data

Indicators of Global Climate Change 2022: annual update of large-scale indicators of the state of the climate system and human influence

Intergovernmental Panel on Climate Change (IPCC) assessments are the trusted source of scientific evidence for climate negotiations taking place under the United Nations Framework Convention on Climate Change (UNFCCC), including the first global stocktake under the Paris Agreement that will conclude at COP28 in December 2023. Evidence-based decision-making needs to be informed by up-to-date and timely information on key indicators of the state of the climate system and of the human influence on the global climate system. However, successive IPCC reports are published at intervals of 5–10 years, creating potential for an information gap between report cycles. We follow methods as close as possible to those used in the IPCC Sixth Assessment Report (AR6) Working Group One (WGI) report. We compile monitoring datasets to produce estimates for key climate indicators related to forcing of the climate system: emissions of greenhouse gases and short-lived climate forcers, greenhouse gas concentrations, radiative forcing, surface temperature changes, the Earth's energy imbalance, warming attributed to human activities, the remaining carbon budget, and estimates of global temperature extremes. The purpose of this effort, grounded in an open data, open science approach, is to make annually updated reliable global climate indicators available in the public domain (https://doi.org/10.5281/zenodo.8000192, Smith et al., 2023a). As they are traceable to IPCC report methods, they can be trusted by all parties involved in UNFCCC negotiations and help convey wider understanding of the latest knowledge of the climate system and its direction of travel. The indicators show that human-induced warming reached 1.14 [0.9 to 1.4] ∘C averaged over the 2013–2022 decade and 1.26 [1.0 to 1.6] ∘C in 2022. Over the 2013–2022 period, human-induced warming has been increasing at an unprecedented rate of over 0.2 ∘C per decade. This high rate of warming is caused by a combination of greenhouse gas emissions being at an all-time high of 54 ± 5.3 GtCO₂e over the last decade, as well as reductions in the strength of aerosol cooling. Despite this, there is evidence that increases in greenhouse gas emissions have slowed, and depending on societal choices, a continued series of these annual updates over the critical 2020s decade could track a change of direction for human influence on climate

Group photograph of three officers, Colonel Edwin C. Mason (left), Colonel Selden Connor, and Major Thomas W. Hyde, 7th ME Infantry

Group photograph of three officers, Colonel Edwin C. Mason (left), Colonel Selden Connor, and Major Thomas W. Hyde, 7th ME Infantry; From the MacDonald Collectionhttps://digitalmaine.com/arc_civilwarportraits/2227/thumbnail.jp