Red blood cell transfusions and iron overload in the treatment of patients with myelodysplastic syndromes

Abstract

BACKGROUNDApproximately 15,000 new cases of myelodysplastic syndromes (MDS) are expected in the United States each year.METHODSThe mainstay for the management of myelodysplastic syndromes (MDS) is supportive therapy with red blood cell (RBC) transfusions to improve the patient's quality of life. RBC transfusions enable adequate tissue oxygenation and increase hemoglobin levels, improve fatigue, and improve the physical and intellectual activity of patients. Up to 90% of patients with MDS will receive RBC transfusions during the course of their disease, and many will become chronically dependent on transfusions to manage their anemia. These transfusions lead to an accumulation of excess iron that, in turn, can develop into a condition known as iron overload, causing clinical consequences like hypertransaminasemia and cirrhosis, dilated cardiomyopathy, and progressive dysfunction of the endocrine glands.RESULTSStudies in patients with MDS have indicated that iron overload because of RBC transfusions was an independent, adverse prognostic factor for overall survival (OS) and leukemia‐free survival (LFS): OS and LFS were significantly shorter in transfusion‐dependent patients with MDS than in those who were not transfusion dependent.CONCLUSIONSAlthough the National Comprehensive Cancer Network guidelines for the treatment of patients with MDS recommend the use of RBC transfusions as supportive care, they further recommend that the iron burden of transfused patients be monitored regularly and that iron chelation therapy be considered to maintain serum ferritin levels of <1000 ng/mL. Cancer 2008. © 2008 American Cancer Society.

Cardiac and cardiovascular consequences after haematopoietic stem cell transplantation

“…In analogy to thalassaemia patients, it seems appropriate to perform iron depletion in long-term survivors with secondary iron overload. Iron overload, documented by liver content >7 mg/g dry weight (Rizzo et al, 2006a) or by serum ferritin >1000-2000 lg/l (Gattermann et al, 2005), should be treated with phlebotomy and/or chelation therapy, in order to maintain serum ferritin level <1000 lg/l (Jabbour et al, 2008). In a general population, proper management of cardiovascular risk factors reduces the risk of cardiovascular events and improves survival.…”

Myelodysplastic syndromes and the role of iron overload

“…13,15 Because up to 90% of patients with MDS will receive RBC transfusions for treatment of anemia, this population is susceptible to problems associated with transfusion dependence and iron overload. 16 Normally, iron redistribution is facilitated by binding to transferrin; however, during long-term transfusion use, plasma iron levels exceed the binding capacity of transferrin, which leads to accumulation of toxic iron amounts in tissue. 15 Elevated iron from long-term transfusion use or disease-related increased dietary iron uptake can lead to persistent oxidative stress, progressive tissue damage, and eventual organ failure (e.g., liver, heart).…”

Changing the Treatment Paradigm in Myelodysplastic Syndromes

“…By regulating body iron levels with iron chelation therapy, the risk of iron overload can be minimized while improving QOL and possibly extending survival. 27 In the last 5 years, newly available therapies have altered the manner in which patients with MDS are managed. Both the immunomodulating agent lenalidomide and the class of agents known as the MTIs have shown potential to alter the biology of disease and, in the case of the MTIs, improve overall survival.…”

“…26,32 More recently, treatment with azacitidine has shown not only durable response rates, but also prolongation in survival compared to other conventional therapies for MDS. [26][27][28] These data have transformed the manner in which therapeutic agents are evaluated in this disease and have altered how the MTIs fit into the treatment paradigm for patients with MDS.…”