Hematology/oncology clinics of North America
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Allogeneic stem cell transplantation currently is the only curative option for severe β-thalassemia and sickle cell disease. Human globin gene therapy with autotransplantation of transduced human hematopoietic stem cells is an exciting alternative approach to a potential cure. ⋯ He has not required blood transfusions for almost 2 years. Most of the patient's gene correction and new human β-globin gene expression is caused by the expansion of a single clone in which the corrective transgene is inserted into an Hmga2 gene.
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Hematol. Oncol. Clin. North Am. · Oct 2010
ReviewGenome-wide association studies of cancer predisposition.
Genome-wide association studies (GWAS) have now been performed in nearly all common malignancies and have identified more than 100 common genetic risk variants that confer a modest increased risk of cancer. For most discovered germline risk variants, the per allele effect size is small (<1.5) and the biologic mechanism of the detected association remains unexplained. ⋯ However, the identified low-penetrance risk variants explain only a small fraction of the heritability of cancer and the clinical usefulness of using these variants for cancer-risk prediction is to date limited. Studies involving more heterogeneous populations, determination of the causal variants, and functional studies are now necessary to further elucidate the potential biologic and clinical significance of the observed associations.
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Hematol. Oncol. Clin. North Am. · Aug 2010
Prevention and treatment of hormone-associated venous thromboembolism: a patient management approach.
Given the known increased risk of venous thromboembolism (VTE) associated with both oral contraceptive (OC) use and hormone replacement therapy (HRT), it is important to address questions about the prevention and management of hormone-associated VTE. Specifically, the objectives of this article are as follows: (1) to provide suggested clinical management approaches for the primary and secondary prevention of VTE for women with thrombophilia; (2) to provide suggested clinical management approaches for the primary and secondary prevention of VTE in the perioperative period for women taking OC or HRT; and (3) to provide practical management approaches for frequently encountered clinical scenarios relating to duration of treatment for hormone-associated VTE.
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Hematol. Oncol. Clin. North Am. · Apr 2010
ReviewLenalidomide for treatment of myelodysplastic syndromes: current status and future directions.
Lenalidomide was approved by the US Food and Drug Administration (FDA) for treatment of transfusion-dependent lower-risk myelodysplastic syndrome patients with deletion (del) (5q) alone or with additional karyotype abnormalities. The approval was based on high rates of prolonged transfusion independence and complete cytogenetic response in this subset. In lower-risk non-del(5q) patients, meaningful erythroid responses also were reported with a low frequency of cytogenetic improvement, although inferior to that observed in the del(5q) patients. ⋯ In del(5q) patients, lenalidomide suppresses the clone by inhibiting the nuclear sequestration of the haplodeficient cell cycle regulatory protein cdc25c, thereby promoting selective G2 arrest and apoptosis. In non-del(5q) patients, lenalidomide enhances erythropoietin receptor signaling. Future directions include use of biologic and molecular markers as predictive tools to select patients and use of combination strategies to overcome resistance to lenalidomide in del(5q) patients or enhance erythropoiesis in non-del 5 patients.