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Leukemias

Managing Iron Overload in Patients with Myelodysplastic Syndromes with Oral Deferasirox Therapy

^aUniversity of Texas MD Anderson Cancer Center, Houston, Texas, USA; ^bAmerican University of Beirut, Beirut, Lebanon

Key Words. Myelodysplastic syndromes • Red blood cell transfusions • Iron overload • Deferasirox • Oral iron chelator

Correspondence: Elias Jabbour, M.D., Department of Leukemia, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, Texas 77030, USA. Telephone: 713-792-7305; Fax: 713-794-4297; e-mail: ejabbour{at}mdanderson.org

Received July 24, 2008; accepted for publication March 9, 2009; first published online in THE ONCOLOGIST Express on April 13, 2009.

Disclosures: Elias Jabbour: Honoraria: Novartis, Bristol-Myers Squibb, speakers' bureau; Guillermo Garcia-Manero: None; Ali Taher: Honoraria: Novartis, speakers' bureau; Hagop M. Kantarjian: None.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Patients with myelodysplastic syndromes (MDS) often require chronic RBC transfusions, which can lead to iron overload. Without adequate management, this may cause progressive damage to hepatic, endocrine, and cardiac organs, significantly affecting overall survival. Recent retrospective analyses have suggested that iron chelation provides a survival advantage in iron-overloaded patients with MDS who are given chelation therapy compared with those who are not. Nonetheless, it is evident that iron overload in many patients with MDS is not adequately managed. Clinical evaluation of the once-daily, oral iron chelator deferasirox in MDS populations has indicated that it provides dose-dependent reductions in body iron burden and is generally well tolerated, with a manageable safety profile in adult and pediatric patients. The most common treatment-related adverse events (AEs) included transient, mild-to-moderate gastrointestinal disturbances and skin rash, which rarely required drug discontinuation and resolved spontaneously in most cases. Adequate management of AEs and practical approaches such as patient education and counseling are necessary to ensure that patients remain compliant with therapy. Regular monitoring of serum ferritin levels is key to identifying patients who require iron chelation therapy, and to ensure maintenance of iron levels below the critical level of 1,000 µg/l. The flexible dosing regimen of deferasirox allows dose adjustments to be made in response to trends in serum ferritin, to changes in a patient's transfusional iron intake, and to the objectives of treatment, allowing the full benefit of transfusion therapy without the risks associated with iron overload.