Pediatr Blood Cancer 2009;52:616–620 Oral Iron Chelation and the Treatment of Iron Overload in a Pediatric Hematology Center Jean L. Raphael, MD, MPH, 1 * M. Brooke Bernhardt, PharmD, 2 Donald H. Mahoney, MD, 1 and Brigitta U. Mueller, MD, MHCM 1 INTRODUCTION Hemoglobinopathies, such as thalassemia and sickle cell disease (SCD), represent a significant category of pediatric transfusion- dependent diseases. Transfusion therapy is mainly used in patients with SCD to reduce the probability of stroke in high-risk populations [1]. In thalassemia, chronic transfusions prevent life-threatening anemia. Despite the benefits of transfusion therapy, it renders patients vulnerable to iron overload. In the absence of treatment, iron overload leads to progressive dysfunction of the heart, liver, and endocrine glands and has significant impact on morbidity and mortality [2–6]. Iron overload is particularly harmful in children because it may cause growth failure and have adverse effects on sexual maturation [5,7–9]. Iron chelation therapy forms an integral component in the management of pediatric transfusion-dependent anemias [10–13]. For decades, deferoxamine has been employed as an effective iron chelator and the standard of care [14,15]. Its poor oral bioavailability and short half-life require that it be administered by subcutaneous or intravenous infusion, usually over 8–12 hr on 5–7 days per week [5]. Patient adherence to this regimen is frequently poor and adversely affects efficacy [16–18]. In 2005, the U.S. Food and Drug Administration approved deferasirox (Exjade 1 , ICL670) for the treatment of patients ages 2 years and older with chronic iron overload secondary to recurrent blood transfusions. Deferasirox is a once-daily oral therapy, which has demonstrated good efficacy and safety in children as well as adults with chronic anemias [19,20]. In well- controlled clinical trials, including all types of anemia, daily doses of 20 or 30 mg/kg/day of deferasirox over 1-year resulted in overall maintenance or reduction of liver iron concentration (LIC). Deferasirox has also demonstrated cost-effectiveness and improved patient satisfaction compared to deferoxamine [21,22]. Availability of an oral iron chelator has been anticipated to improve overall compliance, leading to more effective iron overload control. However, little is known about clinical outcomes with deferasirox outside of clinical trials where efficacy, safety, and compliance are closely controlled and monitored. Here we provide data on the use of deferasirox as standard of care treatment in a large pediatric hematology center. METHODS Study Design We conducted a retrospective chart review to assess the use of deferasirox at the Texas Children’s Hematology Center. The Baylor College of Medicine institutional review board determined this study to be exempt from the requirement for informed consent. Patients All iron overloaded patients primarily followed at the Texas Children’s Hematology Center with any history of deferasirox use comprise the subjects in this study. These include patients with the following diagnoses: SCD, thalassemia, Blackfan-Diamond syndrome, red cell aplasia, sideroblastic anemia, and pyruvate kinase deficiency. Patients who previously participated in a deferasirox clinical trial were included [19]. Study Setting The Texas Children’s Hematology Center is part of a large teaching hospital. Guidelines for initiation of chelation therapy Background. Recent advances have led to the development of oral iron chelators, which have changed clinical practice. The objective of this study was to descriptively assess the use of one such agent, deferasirox, as standard of care treatment in a large pediatric hematology center. Procedure. We retrospectively studied all patients at the Texas Children’s Hematology Center who were previously or currently treated with deferasirox. We gathered data on demographics, clinical diagnoses, length of time on chronic trans- fusions, previous use of deferoxamine, adherence to therapy, and reasons for discontinuation. We also assessed changes in serum ferritin, liver function tests, and creatinine for those on deferasirox for a minimum of 12 months. Results. Fifty-nine patients were studied. Eighty-one percent of patients treated with deferasirox had a diagnosis of sickle cell disease. The mean baseline ferritin level for our study population was 2,117 ng/ml (range 754–7,211). Fifty-three percent of patients had been previously treated with deferoxamine. Adherence to oral therapy was documented in 76% of patients. For those on deferasirox for a minimum of 12 months, serum ferritin decreased in 30% of patients (44% of compliant patients, 11% of poorly compliant patients). Changes in creatinine and liver function tests were mild and did not result in long-term discontinua- tion of deferasirox in any cases. Conclusions. Outside of controlled clinical trials, deferasirox can be utilized safely as an oral iron chelator in children although adherence to therapy and the complex interaction of factors that contribute to iron overload still present challenges for clinicians. Pediatr Blood Cancer 2009;52:616–620. ß 2009 Wiley-Liss, Inc. Key words: anemia; chelation; iron overload ß 2009 Wiley-Liss, Inc. DOI 10.1002/pbc.21929 Published online 15 January 2009 in Wiley InterScience (www.interscience.wiley.com) —————— Abbreviations: LIC, liver iron concentration; SCD, sickle cell disease. 1 Department of Pediatrics, Baylor College of Medicine, Texas Children’s Sickle Cell Center, Houston, Texas; 2 Department of Pharmacy, Texas Children’s Hospital, Houston, Texas *Correspondence to: Jean L. Raphael, Clinical Care Center, Suite D.1540.00, Texas Children’s Hospital, 6621 Fannin Street, Houston, TX 77030. E-mail: Raphael@bcm.edu Received 5 September 2008; Accepted 9 December 2008