Best practice & research. Clinical haematology
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Best Pract Res Clin Haematol · Jan 2005
ReviewThe blue cross blue shield assessment technology review: summary of findings.
Epoetin (EPO; erythropoietin) treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this paper is to review the findings of the 2001 Blue Cross/Blue Shield Association Technology Evaluation Center overview on EPO use in oncology, which served the foundation for the 2002 ASH/ASCO clinical guideline on this subject. The BC/BS review had two major aims: (1) to quantify the effects of EPO on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia, and (2) to evaluate whether outcomes are superior when EPO treatment is initiated at higher hemoglobin thresholds. ⋯ The review concluded that EPO reduced the odds of transfusion for cancer patients undergoing therapy. Evidence was insufficient to determine whether initiating EPO earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10g/dL. An update of this review, which includes information on quality of life, transfusion requirment, survival and tumor response, for first and second-generation epoetin products is ongoing.
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Best Pract Res Clin Haematol · Sep 2004
ReviewGlobin gene transfer for treatment of the beta-thalassemias and sickle cell disease.
The beta-thalassemias and sickle cell disease are severe congenital anemias that are caused by mutations that alter the production of the beta chain of hemoglobin. Allogeneic hematopoietic stem cell (HSC) transplantation is curative, but this therapeutic option is not available to the majority of patients. The transfer of a functional globin gene in autologous HCSs thus represents a highly attractive alternative treatment. ⋯ Several groups have now confirmed and extended these findings in various mouse models of severe hemoglobinopathies, thus generating enthusiasm for a genetic treatment based on globin gene transfer. Furthermore, globin vectors represent a general paradigm for the regulation of transgene function and the improvement of vector safety by restricting transgene expression to the differentiated progeny within a single lineage, thereby reducing the risk of activating oncogenes in hematopoietic progenitors. Here we review the principles underlying the genesis of regulated vectors for stem cell therapy.
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Best Pract Res Clin Haematol · Mar 2004
ReviewNatural anticoagulant inhibitors: activated Protein C.
Protein C is a vitamin-K-dependent zymogen, whose congenital deficiency state leads to increased risk for venous thrombosis. Activated Protein C (aPC) exerts its anticoagulant function by inhibiting the cofactors in the clotting cascade, Factors Va and VIIIa. In addition, aPC displays anti-inflammatory, anti-apoptotic and profibrinolytic activities. ⋯ The major toxicity associated with treatment is bleeding. Appropriate use of rhAPC depends on an understanding of its mechanisms of action and risk:benefit profile. The goals of this review are: to describe the Protein C pathway; to discuss the definitions, epidemiology and pathophysiology of severe sepsis; to provide a conceptual framework for understanding the role of rhAPC in this syndrome; and to address frequently asked questions about the day-to-day use of this agent.
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Best Pract Res Clin Haematol · Sep 2003
ReviewRetinoic acid syndrome: manifestations, pathogenesis, and treatment.
All-trans retinoic acid (ATRA) is a potent differentiation agent that is effective therapy in acute promyelocytic leukaemia. Although ATRA is generally well tolerated, some patients develop retinoic acid syndrome. ⋯ However, if identified early enough, effective therapy can be administered. This chapter discusses the clinical aspects and pathogenesis of retinoic acid syndrome.
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Monoclonal antibodies (mAb) have dramatically advanced our ability to treat non-Hodgkin's lymphoma (NHL), and there has been a virtual explosion of clinical data regarding their use. Rituximab is a humanized anti-CD20 mAb and has significant single agent activity in follicular lymphoma, and to a lesser extent in mantle-cell and diffuse large B-cell lymphoma (DLCL). Rituximab appears to have synergistic activity with cytotoxic chemotherapy and the combination has recently demonstrated improved rates of complete remission (CR) and overall survival in older patients with DLCL. ⋯ Myelosuppression is more significant however, and their place in the treatment algorithm remains to be clearly defined. Other immunotoxins (e.g. BL22) and mAb against alternate targets (e.g. epratuzumab, humanized anti-CD22) are in development.