Should Patients with Myelodysplastic Syndromes Undergo Iron Chelation Therapy? New Data Answering the Question

Should Patients with Myelodysplastic Syndromes Undergo Iron Chelation Therapy? New Data Answering the Question

Goldberg Stuart L
US Hematology Volume 2
Published: January 2010
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Abstract
Although it is well established that transfusional iron overload leads to organ impairment and shortened survival among children with thalassemia and sickle cell anemia, the role of transfusional iron overload and its treatment among older individuals with the myelodysplastic syndromes (MDS) remains unclear. Recent reviews have noted that MDS patients requiring frequent red blood cell transfusions experience higher rates of cardiac, hepatic, endocrine, and other organ damage in patterns similar to pediatric transfusional hemochromatosis, with increased rates of transformation to leukemia and decreased survival. Through the use of prognostic scoring systems such as the International Prognostic Scoring System (IPSS) and the World Health Organization (WHO) classification-based prognostic scoring system (WPSS), MDS patients with projected survivals long enough to warrant concern about the toxicities of iron overload can be identified and iron chelation therapies can be considered. The results of two large prospective trials among transfusion-dependent MDS patients, US03 and EPIC, have demonstrated that the oral iron chelation agent deferasirox can successfully reduce iron content and has an acceptable safety profile in this elderly population. Furthermore, retrospective trials have suggested that iron chelation therapy may prolong survival in MDS, and prospective trials are being planned. This article will highlight some of these issues.

Keywords
Iron overload, red blood cell transfusion, myelodysplastic syndromes, iron chelation, deferasirox

Disclosure: Stuart L Goldberg, MD, is on the speaker’s bureau and receives research support from Novartis Oncology.
Received: April 17, 2009 Accepted: May 18, 2009
Correspondence: Stuart L Goldberg, MD, 20 Prospect Avenue, Suite 400 Hackensack NJ 07601. E: sgoldberg@humed.com

Support: Supported by Novartis Pharmaceuticals Corporation.

The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis in one or more cell lines, leading to peripheral cytopenias with a tendency to develop into acute leukemia. Supportive care with red blood cell (RBC) transfusions is the mainstay of treatment, although newer ‘low-intensity strategies’ such as hypomethylating and immunomodulatory agents are changing treatment patterns. With repeated transfusions comes the risk of transfusional iron overload. However, should patients with MDS undergo iron chelation therapy (ICT)? New data are available that can help to answer this question.

Do Patients with Myelodysplastic Syndromes Suffer Organ Impairment from Iron Overload or Is this Identified Only in Children with Thalassemia or Sickle Cell Anemia?
Transfusion-related hemochromatosis has been identified in elderly MDS patients who are transfusion-dependent. A retrospective study of 46 MDS patients who had received >50 units of RBC transfusions noted evidence of cardiac disease in >40% of patients, arrhythmias in 10, and 14 deaths from intractable congestive heart failure. Evidence of hepatic enzyme abnormalities occurred in approximately 25% of patients, and evidence of new endocrine effects was identified in approximately 10% of individuals.1 An Italian series also identified a high rate of cardiac, diabetes/glucose intolerance, and hepatic enzyme abnormalities among 26 heavily transfused patients. Transfusion requirements >2 units per month were correlated with increased organ toxicity.2 A retrospective study from Japan of 292 patients (52% MDS, 31% aplastic anemia) followed over a course of four years noted that >90% of the patients who had a ferritin level >1,000mcg/l had evidence of hepatic enzyme insufficiency (elevation in serum glutamic pyruvic transaminase/serum glutamic oxaloacetic transaminase [SGPT/SGOT]). Among the 75 deaths in this group of patients, the individuals who died from chronic liver failure or cardiac disease had received significantly more transfusions than those patients who died from other causes.3

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Keywords:
Iron overload, red blood cell transfusion, myelodysplastic syndromes, iron chelation, deferasirox, Iron overload diagnosis, Iron overload sickle cell, Iron overload fatigue, Iron overload disease, Iron overload symptoms, Iron overload blood transfusion, red blood cells hematocrit, red blood cells clotting, anemia red blood cells, hemoglobin red blood cells, erythropoietin red blood cells, red blood cells platelets, myelodysplastic syndromes symptoms, refractory anemia with excess blasts, 5q meloidysplastic syndrome, myelodysplastic syndrome leukemia, myelodysplastic syndromes thrombocytopenia, iron chelation therapy, iron chelation agents, oral iron chelator, serum ferritin, serum creatinine,

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