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Related Collections Red Cells Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 October 2000, Vol. 96, No. 7, pp. 2379-2384 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS 2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia Mabel Koshy, Louise Dorn, Linda Bressler, Robert Molokie, Donald Lavelle, Nasrin Talischy, Ronald Hoffman, Wendy van Overveld, and Joseph DeSimone From the University of Illinois at Chicago, Chicago, IL; VA Chicago West Side Division, Chicago, IL; Pharmachemie BV, Haarlem, The Netherlands. Augmentation of the fetal hemoglobin (HbF) levels is of therapeutic benefit in patients with sickle cell anemia. Hydroxyurea (HU), by increasing HbF, lowers rates of pain crisis, episodes of acute chest syndrome, and requirements for blood transfusions. For patients with no HbF elevation after HU treatment, augmentation of HbF levels by 5-aza-2'-deoxycytidine (5-aza-CdR, decitabine) could serve as an alternate mode of treatment. Eight adult patients participated in a dose-escalating phase I/II study with 5-aza-CdR at doses ranging from 0.15 to 0.30 mg/kg given 5 days a week for 2 weeks. HbF, F cell, F/F cell, -globin synthesis ratio, complete blood count, and chemistry were measured. The average -globin synthesis relative to non--globin synthesis prior to therapy was 3.19% ± 1.43% and increased to 13.66% ± 4.35% after treatment. HbF increased from 3.55% ± 2.47% to 13.45% ± 3.69%. F cells increased from 21% ± 14.8% to 55% ± 13.5% and HbF/F cell increased from 17% to 24%. In the HU nonresponders HbF levels increased from 2.28% ± 1.61% to 2.6% ± 2.15% on HU, whereas on 5-aza-CdR HbF increased to 12.70% ± 1.81%. Total hemoglobin increased by 1 g/dL in 6 of 8 patients with only minor reversible toxicities, and all patients tolerated the drug. Maximum HbF was attained within 4 weeks of treatment and persisted for 2 weeks before falling below 90% of the maximum. Therefore 5-aza-CdR could be effective in increasing HbF in patients with sickle cell anemia who failed to increase HbF with HU. Demonstration of sustained F levels with additional treatment cycles without toxicity is currently being performed. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Lavelle, Y. Saunthararajah, and J. DeSimone DNA methylation and mechanism of action of 5-azacytidine Blood, February 15, 2008; 111(4): 2485 - 2485. [Full Text] [PDF] H. Fathallah, R. S. Weinberg, Y. Galperin, M. Sutton, and G. F. 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