Leukemia Research 34 (2010) 1560–1565 Contents lists available at ScienceDirect Leukemia Research journal homepage: www.elsevier.com/locate/leukres Prospective assessment of effects on iron-overload parameters of deferasirox therapy in patients with myelodysplastic syndromes Peter L. Greenberg a,∗ , Charles A. Koller b , Z. Ioav Cabantchik c , Ghulam Warsi d , Tara Glynos d , Carole Paley d , Charles Schiffer e a Division of Hematology, Stanford University Cancer Center, Stanford, CA, USA b MD Anderson Cancer Center, Houston, TX, USA c Hebrew University, Jerusalem, Israel d Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA e Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA article info Article history: Received 5 March 2010 Received in revised form 15 June 2010 Accepted 15 June 2010 Available online 8 July 2010 Keywords: Iron chelation Deferasirox Exjade ® MDS Pharmacokinetics MRI abstract We report the first prospective study evaluating the effects of deferasirox on liver iron concentration (LIC), labile plasma iron (LPI) and pharmacokinetics (PK) along with serum ferritin values in patients with IPSS Low- and Intermediate-1 risk myelodysplastic syndromes (MDS) and evidence of iron over- load. Twenty-four heavily transfused MDS patients were enrolled in a planned 52 weeks of therapy. PK studies showed dose-proportional total drug exposure. Data demonstrated that deferasirox was well tol- erated and effectively reduced LIC, LPI and serum ferritin in the iron-overloaded patients with MDS who completed 24 and 52 weeks of therapy despite ongoing receipt of red blood cell transfusions. © 2010 Elsevier Ltd. All rights reserved. 1. Introduction The management of patients with myelodysplastic syndromes (MDS) requires general supportive care and therapies that specif- ically attempt to alter hematopoietic defects in the disease. Supportive care measures include antibiotic treatment and trans- fusion with red blood cells (RBC) and platelets to ameliorate the patients’ symptomatic cytopenias [1]. In addition, because of the large number of RBC transfusions often needed for the patients’ symptomatic anemia and the ineffective erythropoiesis ongoing in MDS, tissue iron overload may frequently become a prominent clinical feature [2]. The pathophysiologic effects of iron overload relate to increased non-transferrin-bound iron (NTBI) generating toxic oxygen free radicals, which may be associated with the adverse clinical effects of chronic iron overload on car- diac, hepatic and endocrine function [3,4]. Anemic lower-risk ∗ Corresponding author at: Hematology Division, Stanford University Cancer Cen- ter, 875 Blake Wilbur Drive, Room 2335, Stanford, CA 94305, USA. Tel.: +1 650 725 8355; fax: +1 650 723 1269. E-mail address: peterg@stanford.edu (P.L. Greenberg). MDS patients who have undergone poly-transfusion have shown increased levels of plasma NTBI associated with increased inef- fective erythropoiesis [5]. Labile plasma iron (LPI), the redox active and chelatable component of NTBI, causes the labile cell iron to increase, resulting in peroxidative damage to mem- brane lipids and proteins and ensuing tissue and organ damage [6,7]. Studies in -thalassemia major have clearly demonstrated that the consequences of iron overload can be prevented or reversed by effective chelation regimens [8,9]. Retrospective studies have shown that iron overload has a negative impact on the morbid- ity and mortality of transfusion-dependent patients with MDS [10,11]. Other reports of non-controlled trials have demonstrated the possible beneficial effects of iron chelation therapy on patient survival [12,13]. Recent investigations have shown the efficacy and safety of deferasirox for chelating iron in patients with thalassemia and in those with a variety of chronic anemias, including a small group of patients with MDS [14]. Effective iron chelation therapy is capable of reducing levels of serum ferritin, liver iron concen- tration (LIC) [15] and LPI [6,7] in patients with thalassemia. In addition, non-invasive magnetic resonance technology has recently demonstrated the use of R2 magnetic resonance imaging (MRI) to 0145-2126/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2010.06.013