Regular erythrocyte transfusions form the cornerstone of treatmentfor patients with severe -thalassemia. Despite the use of iron-chelationtherapy, fatal iron overload develops in many patients, evenwhen they are under supervision and taking part in studies designedto test the effectiveness of intense chelation1,2. Another potentialconsequence of long-term transfusions is the development ofantierythrocyte antibodies, making effective transfusion difficultor, in rare cases, impossible3,4,5,6.
A potential alternative to transfusion is the use of the nucleosideanalogue azacitidine to stimulate transcription of the fetalglobin genes by pharmacologic means and thus lead to more effectiveerythropoiesis7,8,9,10,11,12. . . . [Full Text of this Article]
Methods
Case Reports
Patient 1
Patient 2
Patient 3
Results
Patient 1
Patient 2
Patient 3
Hematologic Responses
Side Effects of Azacitidine
Discussion
Source Information
From the Section of Hematology and Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, N.H. (C.H.L.), and the Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. (A.W.N.).
Address reprint requests to Dr. Lowrey at the Section of Hematology and Oncology, Dartmouth-Hitchcock Medical Center, One Medical Center Dr., Lebanon, NH 03756.
References
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18: 415-421
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Koshy, M., Dorn, L., Bressler, L., Molokie, R., Lavelle, D., Talischy, N., Hoffman, R., van Overveld, W., DeSimone, J.
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Smith, R. D., Li, J., Noguchi, C. T., Schechter, A. N.
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-thalassemia. Despite the use of iron-chelation therapy, fatal iron overload develops in many patients, even when they are under supervision and taking part in studies designed to test the effectiveness of intense chelation1,2. Another potential consequence of long-term transfusions is the development of antierythrocyte antibodies, making effective transfusion difficult or, in rare cases, impossible3,4,5,6. 
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