Expert opinion on biological therapy
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Expert Opin Biol Ther · Jan 2014
ReviewCAR-modified anti-CD19 T cells for the treatment of B-cell malignancies: rules of the road.
Malignancies of the B lymphocyte or its precursor include B-cell non-Hodgkin lymphoma as well as chronic and acute lymphoid leukemias. These are among the most common hematologic malignancies and many patients with B-cell malignancies are incurable. Although most patients initially respond to first-line treatment, relapse is frequent and is associated with a poor prognosis. T cells that are genetically engineered to express chimeric antigen receptors (CARs) recognizing the B-cell-associated molecule CD19 have emerged as a potentially potent and exciting therapeutic modality in recent years. ⋯ Genetic engineering of T cells has become clinically feasible and appears to be safe. Here we provide an insight into the process of patient selection, engineered T-cell production, infusion procedure, expected toxicities and efficacy of this exciting approach as it is practiced in the treatment of B-cell malignancies. Anti-CD19-redirected T cells likely represent the vanguard of an exciting new approach to treating cancer.
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Expert Opin Biol Ther · Jan 2014
ReviewEffectiveness and safety of erythropoiesis-stimulating agent use in the perioperative period.
Erythropoiesis-stimulating agents (ESAs) are widely used in treating anemia associated with renal failure. They are also now used perioperatively to reduce the use of allogeneic blood transfusions (ABTs) in patients undergoing surgery with anticipated high blood loss. Although they can reduce the risks associated with ABT and improve quality of life, the use of ESAs is still associated with adverse effects. ⋯ Current evidence supports the use of perioperative ESAs to reduce the need for ABT. However, large studies assessing safety in anemic patients with chronic renal disease have found adverse effects including cardiovascular, stroke and thromboembolic events. However, whether these concerns can be conferred onto the surgical population remains to be seen as the perioperative dosing strategies have been more variable in timing, dose and duration in comparison with those used for chronic diseases. Future research needs to address the questions of optimal dosing strategies in order to maximize the positive effects and minimize adverse events.
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Alemtuzumab is a humanized IgG1 kappa monoclonal antibody approved for treatment of B-cell chronic lymphocytic leukemia. This cytolytic antibody is directed against CD52 and depletes lymphocytes, with monocytes, macrophages, natural killer cells and a subpopulation of granulocytes being affected to a much lesser degree. Alemtuzumab is currently under review to treat relapsing multiple sclerosis (MS) in the United States, based on positive Phase II and Phase III trials in both treatment-naïve and treated relapsing MS patients. There was excellent efficacy in suppressing both clinical and neuroimaging disease activities. In these trials, the comparator arm was not placebo, but high dose frequently dosed subcutaneous interferon beta 1a. Alemtuzumab has recently been approved by the European authorities for active relapsing MS, in essence as a first-line agent. It produces long-standing effects, consistent with an induction agent. Efficacy will have to be weighed against risk of adverse effects, which include autoimmune disorders and infection. Alemtuzumab joins an increasingly crowded market, and will add to the complexity of treating MS. ⋯ Alemtuzumab offers induction strategy for very active relapsing MS patients who have failed conventional therapy, and possibly selected treatment-naive patients. Alemtuzumab use is likely to be restricted to specialized MS centers, with long-term monitoring to determine the true risk for adverse effects.