Hematology/oncology clinics of North America
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Hematol. Oncol. Clin. North Am. · Aug 2014
ReviewTransfusional iron overload and iron chelation therapy in thalassemia major and sickle cell disease.
Iron overload is an inevitable consequence of blood transfusions and is often accompanied by increased iron absorption from the gut. Chelation therapy is necessary to prevent the consequences of hemosiderosis. Three chelators, deferoxamine, deferiprone, and deferasirox, are presently available and a fourth is undergoing clinical trials. ⋯ Also, many studies have shown the efficacy of the combination of deferoxamine plus deferiprone as an intensive treatment of severe iron overload. Alternating chelators can reduce adverse effects and improve compliance. Adherence to therapy is crucial for good results.
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Since the development and approval of Ipilimumab, the first immune checkpoint inhibitor licensed for the treatment of metastatic melanoma, clinicians have gained a better understanding of the mode of action, management of toxicities, and assessment of response to this class of drugs. Several antibodies are now in development, aimed at blocking novel immune checkpoint molecules, such as PD-1 and it's corresponding ligand PD-L1. This article summarizes the mechanism of action, preclinical development, and subsequent clinical studies of immune checkpoint antibodies in melanoma.
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Hematol. Oncol. Clin. North Am. · Apr 2014
ReviewIschemia-reperfusion injury in sickle cell anemia: relationship to acute chest syndrome, endothelial dysfunction, arterial vasculopathy, and inflammatory pain.
Ischemia-reperfusion (I/R) physiology, also called reperfusion injury, instigates vascular and tissue injury in human disease states. This review describes why sickle cell anemia should be conceptualized in this fashion and how I/R physiology explains the genesis of characteristic aspects of vascular pathobiology and clinical disease in sickle cell anemia. The nature of I/R and its relevance to sickle cell anemia are discussed, with an emphasis on the acute chest syndrome, endothelial dysfunction with aberrant vasoregulation, circle of Willis vasculopathy, and inflammatory pain. Viewing sickle disease from this perspective elucidates defining pathophysiology and identifies a host of novel potential therapeutic targets.
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Hematol. Oncol. Clin. North Am. · Apr 2014
ReviewGene therapy for hemoglobinopathies: the state of the field and the future.
After nearly two decades of struggle, gene therapy for hemoglobinopathies using vectors carrying β or γ-globin gene has finally reached the clinical doorsteps. This was made possible by advances made in our understanding of critical regulatory elements required for high level of globin gene expression and improved gene transfer vectors and methodologies. Development of gene editing technologies and reprogramming somatic cells for regenerative medicine holds the promise of genetic correction of hemoglobinopathies in the future. This article will review the state of the field and the upcoming technologies that will allow genetic therapeutic correction of hemoglobinopathies.
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Hematol. Oncol. Clin. North Am. · Feb 2014
ReviewBrentuximab vedotin for the treatment of patients with Hodgkin lymphoma.
Hodgkin lymphoma (HL) is a relatively rare but highly curable human cancer. Because very few patients relapse and will require subsequent therapy, new drug development for HL has not been seen as a high priority by the pharmaceutical industry. Brentuximab vedotin, an antibody-drug conjugate that targets CD30 receptors, became the first drug to be approved by regulatory agencies for the treatment of HL in more than 30 years. This review summarizes the current and future directions of incorporating brentuximab vedotin in the management of patients with HL.