Invited editorialIron overload in myelodysplastic syndromes: A Canadian consensus guideline
Introduction
The prevalence of MDS has not been rigorously documented, although a recent analysis suggests it may affect as many as one in 1000 Canadians over the age of 65 years [1]. The main clinical feature of MDS is anemia, which is present in about 80% of patients at diagnosis and varies in severity. Although novel therapies are being developed that enhance bone marrow function and reduce or obviate the need for blood transfusion, currently more than 80% of MDS patients require chronic red blood cell transfusion as the cornerstone of treatment [2]. As a consequence, transfusional iron overload is a very common complication of MDS. It is widely thought that this complication of MDS is physiologically important and that the use of iron chelation therapy to prevent or ameliorate iron overload is a key consideration in the management of MDS patients [3], although this is not universally accepted. In this paper we provide a critical review of the basis in evidence for iron chelation in MDS, and provide guidelines for clinical practice.
Section snippets
Methodology
In December 2005, the Expert Panel reviewed national and international data on the contribution of transfusional iron overload to the morbidity and mortality of patients with MDS, the underlying pathology of iron-related tissue and organ damage, and the current evidence for iron chelation therapy in patients with MDS. The panel examined existing clinical guidelines, discussed standard practices in Canada, and devised a comprehensive outline to guide their investigation. This work focused on the
Why treat iron overload in patients with MDS?
Since each unit of red blood cells (RBCs) contains 200–250 mg of iron, approximately 100 times the normal daily iron flux, patients who require chronic blood transfusions are prone to develop iron overload. In addition to transfusional iron loading, MDS patients have increased intestinal absorption of iron, similar to patients with hemoglobinopathies and genetic hemaochromatosis (HH) [5]. Hence, MDS patients may show evidence of iron loading even prior to initiation of transfusion therapy.
Iron
When and in whom should iron chelation therapy be initiated?
Iron overload is an inevitable consequence of chronic transfusion therapy without concomitant blood (or iron) loss (e.g., angiodysplasia). The principle of iron chelation in MDS is to prevent the occurrence of iron-induced organ damage, thereby avoiding excess morbidity and mortality. Iron chelation should start before organ damage occurs in patients in whom the rate of transfusion and iron loading predict physiologically important tissue iron deposition. However, due to the clinical
How to treat iron overload in patients with MDS?
Once the decision to treat is reached, the literature provides no specific evidence-based studies of high quality to guide the best approach to treating patients with MDS and transfusion-related iron overload. As shown above, this population represents only a minority of patients in studies of iron chelation, which include patients with diverse hematological diseases, are usually comprised of small numbers of patients, and are often retrospective analyses or phase II studies.
Three available
Summary
The recommendations presented in this paper are based, for the most part, upon low-level evidence and extrapolation from data in other diseases, particularly thalassemia major, where iron chelation therapy has resulted in stunning improvements in quality and length of life. It would be of great value to have data from a prospective randomized assessment of the effects of iron chelation therapy on morbidity, mortality, quality of life, transfusion needs, and the rate of leukemic transformation.
Acknowledgements
The preparation of this guideline was supported by Novartis Canada, who provided an educational grant and logistical support for meetings and literature review. The authors thank Ms. Jennifer Burton for assistance in creating the Fig. 1.
Contributions. Richard A. Wells chaired consensus panel, coordinated literature review and panel meetings, drafted “When to treat” and “How to treat” sections, reviewed and edited all manuscript sections, wrote final manuscript. Brian F. Leber reviewed
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