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

Poprawa własności mechanicznych stopów wolframu spiekanych z udziałem fazy ciekłej poprzez kontrolowane chłodzenie

Heavy alloys with 90 and 93 w/o W and a 7:3 Ni: Fe ratio are usually produced by the liquid phase sintering of W, Ni, and Fe powder mixtures. The result is a two-phase microstructure of spherical W solid solution grains embedded in a matrix of Ni rich solid solution. UTS, elongation, and microstructure strongly depend on the composition of the atmosphere during liquid phase sintering, on the cooling conditions and/or on the composition of the protective atmosphere during the heat treatment and its cooling conditions if treatment was applied after sintering. The sintering atmosphere is usually hydrogen. This can assure a proper densification but in the same time it can give rise to embitterment of W/matrix boundaries accompanied by a drastically decreasing ductility. In order to avoid this effect, heat treatments are applied in a neutral atmosphere (Ar, N2, Ar+N2, etc.) to completely or partially remove the hydrogen from the sintered material. This paper studies the effect of protective atmosphere and cooling conditions on the UTS, elongation and microstructure of the above-mentioned two heavy alloys.Ciężkie stopy o zawartości 90 i 93%.wag W i stałym stosunku Ni do Fe wynoszącym 7:3 są zwykle wytwarzane przez spiekania z udziałem fazy ciekłej mieszaniny proszków W, Ni i Fe. Rezultatem jest dwufazowa mikrostruktura sferycznych ziaren roztworu stałego W, osadzonych w matrycy bogatego w Ni roztworu stałego. Wytrzymałość na rozciąganie, wydłużenie, i mikrostruktura silnie zależą od składu atmosfery podczas spiekania z udziałem fazy ciekłej, od warunków chłodzenia i/lub składu atmosfery ochronnej podczas obróbki cieplnej i warunków chłodzenia, jeśli zostało zastosowane po spiekaniu. Spiekanie prowadzone jest zwykle w atmosferze wodoru, która zapewnia odpowiednie zagęszczenie, ale jednocześnie może doprowadzić do zadrażnień na granicach ziaren W/osnowa, czemu towarzyszy drastycznie zmniejszenie ciągliwości. Żeby uniknąć tego efektu, obróbka cieplna prowadzona jest w atmosferze obojętnej (Ar, N2, Ar + N2 itp.), żeby częściowo lub całkowicie usunąć wodór ze spiekanego materiału. W pracy badano wpływ atmosfery ochronnej i warunków chłodzenia na wytrzymałość na rozciąganie, wydłużanie i mikrostrukturę wyżej wymienionych stopów

Financial services liberalization and international integration in South Eastern Europe

The first part of this paper analyses the regulatory framework for international trade in financial services within the auspices of the World Trade Organization (WTO), with special attention paid to the open issues including the scope of prudential measures and capital mobility limitations. The process of the international integration of the South Eastern Europe (SEE) countries is mainly dictated by their goal of EU integration. With regard to the services' sectors, a major liberalization step on the way is WTO accession. Of the countries in the region only Serbia, Bosnia and Herzegovina and Montenegro are still not WTO members and in order to become members significant liberalization commitments will be demanded of them. For this reason the second part of the paper deals with concrete financial liberalization commitments undertaken by the original WTO members in SEE and the newly WTO acceded SEE member countries. The last part of the paper provides a quantitative analysis of these commitments by means of the measurement of liberalization indices in the banking sectors in SEE countries. This is to provide a general idea of the scope of liberalization that may be required from a SEE country in order to achieve WTO membership on the road to EU integration

PET-Based Staging Is Cost-Effective in Early-Stage Follicular Lymphoma

The objective was to assess the cost-effectiveness of staging PET/CT in early-stage follicular lymphoma (FL) from the Canadian health-care system perspective. Methods: The study population was FL patients staged as early-stage using conventional CT imaging and planned for curative-intent radiation therapy (RT). A decision analytic model simulated the management after adding staging PET/CT versus using staging CT alone. In the no-PET/CT strategy, all patients proceeded to curative-intent RT as planned. In the PET/CT strategy, PET/CT information could result in an increased RT volume, switching to a noncurative approach, or no change in RT treatment as planned. The subsequent disease course was described using a state-transition cohort model over a 30-y time horizon. Diagnostic characteristics, probabilities, utilities, and costs were derived from the literature. Baseline analysis was performed using quality-adjusted life years (QALYs), costs (2019 Canadian dollars), and the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were conducted, evaluating net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Probabilistic sensitivity analysis using 10,000 simulations was performed. Costs and QALYs were discounted at a rate of 1.5$3,165 and a gain of 0.32 QALYs. In deterministic sensitivity analyses, the PET/CT strategy remained the preferred strategy for all scenarios supported by available data. In probabilistic sensitivity analysis, the PET/CT strategy was strongly dominant in 77% of simulations (i.e., reduced cost and increased QALYs) and was cost-effective in 89% of simulations (i.e., either saved costs or had an incremental cost-effectiveness ratio below $100,000/QALY). Conclusion: Our analysis showed that the use of PET/CT to stage early-stage FL patients reduces cost and improves QALYs. Patients with early-stage FL should undergo PET/CT before curative-intent RT.</p