Azacitidine in the Management of Patients With Myelodysplastic Syndromes.

Azacitidine in the management of patients with myelodysplastic syndromes.

Ther Adv Hematol. 2012 Dec; 3(6): 355-73
Khan C, Pathe N, Fazal S, Lister J, Rossetti JM

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoeitic disorders characterized by ineffective hematopoiesis and potential transformation to acute myeloid leukemia (AML). For decades, the mainstay of treatment for MDS was supportive care, including transfusion of blood products and growth factors. Further understanding of disease biology led to the discovery of a high prevalence of hypermethylation of tumor suppressor genes in high-risk MDS and secondary leukemias. Hence, the role of irreversible DNA methlytransferase inhibitors such as azacitidine was investigated with promising outcomes in the treatment of MDS. Azacitidine was initially approved in the USA by the Food and Drug Administration (FDA) in 2004 for the treatment of all subtypes of MDS and was granted expanded approval in 2009 to reflect new overall survival data demonstrated in the AZA-001 study of patients with higher-risk MDS. Azacitidine has demonstrated significant and clinically meaningful prolongation of survival in higher-risk patients with MDS and has changed the natural history of these disorders. The agent maintains a relatively safe toxicity profile, even in older patients. The role of azacitidine has been explored in the treatment of AML and chronic myelomonocytic leukemia and has also been studied in the peritransplant setting. Azacitidine has been combined with other novel agents such as lenalidomide, histone deacetylase inhibitors and growth factors in the hope of achieving improved outcomes. Currently, both intravenous and subcutaneous forms of azacitidine are approved for use in the USA with the oral form being granted fast track status by the FDA. HubMed – drug

Ruxolitinib: a potent and selective Janus kinase 1 and 2 inhibitor in patients with myelofibrosis. An update for clinicians.

Ther Adv Hematol. 2012 Dec; 3(6): 341-54
Harrison C, Vannucchi AM

Ruxolitinib became the first US Food and Drug Administration approved therapy for myelofibrosis in 2011 and EU approval is anticipated in summer 2012. Two large phase III trials (known as the COMFORT studies) were the basis for this approval and were published recently. In this review article we discuss the challenges in managing myelofibrosis, the information to date about ruxolitinib and speculate as to the future direction with this and similar agents. HubMed – drug

Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia.

Ther Adv Hematol. 2012 Aug; 3(4): 237-51
Bakchoul T, Greinacher A

Heparin-induced thrombocytopenia (HIT) is a drug-mediated, prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After their binding to PF4/heparin complexes on the platelet surface, HIT antibodies are capable of intravascular platelet activation by cross-linking Fc? receptor IIA leading to a platelet count decrease and/or thrombosis. Diagnosis of HIT is often difficult. This, and the low specificity of the commercially available immunoassays, leads currently to substantial overdiagnosis of HIT. Timing of onset, the moderate nature of thrombocytopenia, and the common concurrence of thrombosis are very important factors, which help to differentiate HIT from other potential causes of thrombocytopenia. A combination of a clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. Although HIT is considered to be a rare complication of heparin treatment, the very high number of hospital inpatients, and increasingly also hospital outpatients receiving heparin, still result in a considerable number of patients developing HIT. If HIT occurs, potentially devastating complications such as life-threatening thrombosis make it one of the most serious adverse drug reactions. If HIT is strongly suspected, all heparin must be stopped and an alternative nonheparin anticoagulant started at a therapeutic dose to prevent thromboembolic complications. However, the nonheparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. While established drugs for HIT are disappearing from the market (lepirudin, danaparoid), bivalirudin, fondaparinux and potentially the new anticoagulants such as dabigatran, rivaroxaban and apixaban provide new treatment options. HubMed – drug