Premium
SI33
Implications and Management of Iron Overload in Myelodysplastic Syndromes
Author(s) -
Malcovati L.
Publication year - 2006
Publication title -
transfusion medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.471
H-Index - 59
eISSN - 1365-3148
pISSN - 0958-7578
DOI - 10.1111/j.1365-3148.2006.00693_45.x
Subject(s) - medicine , cytopenia , myelodysplastic syndromes , ferritin , anemia , ineffective erythropoiesis , population , bone marrow , gastroenterology , intensive care medicine , pediatrics , erythropoiesis , environmental health
According to evidence‐ and consensus‐based practice guidelines, the majority of patients with myelodysplastic syndrome (MDS) should receive supportive therapy at present. Once anemia is symptomatic, red cell transfusions are the mainstay of therapy. The life expectancy of patients with isolated erythroid dysplasia aged 70 years or older is not significantly shorter than that of the general population; avoiding disease complication is therefore very important in these individuals. Recently we demonstrated that the development of red cell transfusion‐dependency significantly affects survival of MDS patients (Malcovati et al . J Clin Oncol 2005; 23: 7594–603). This partly reflects the severity of bone marrow failure; however, development of secondary iron overload significantly worsens survival of transfusion‐dependent patients. Considering patients with transfusion needs, iron overload (defined as serum ferritin above 1000 ng mL −1 ) is developed after receiving a median number of 20–25 RBC units. The effect of iron overload is mainly noticeable among patients with refractory anemia, who have a longer survival and therefore are more prone to develop the adverse effects of iron overload. In contrast, secondary iron overload does not affect the survival of patients with refractory cytopenia, who have a median survival of about 50 months. The negative effect of iron overload is significantly associated with serum ferritin levels, with a 40% increase in hazard for every 500 ng mL ‐1 of increase in serum ferritin. According to the currently available therapeutic guidelines iron chelation should be considered once a patient has received 20–50 units of red cells, but only in patients for whom long‐term transfusion therapy is likely, or when an allogeneic stem cell transplantation is planned. The target serum ferritin concentration should be <1000 ng mL ‐1 . Desferrioxamine 20–40 mg kg ‐1 per day should be administered by 12 h subcutaneous infusion or by two daily subcutaneous bolus administrations for 5 days per week. Recently, deferasirox (ICL670) has proved to be an effective oral iron chelator in patients with thalassemia major and in those with MDS. In 2005, the USA Food and Drug Administration has approved deferasirox for treatment of chronic iron overload due to multiple blood transfusions. A European Medicines Agency (EMEA) decision is waited in 2006.