Leitch and Vickars identify survival benefits of iron chelation

Myelodysplastic syndromes and primary myelofibrosis are bone marrow failure disorders with a heightened leukemia risk. Affected patients require chronic red blood cell transfusions which leads to iron overload. Excess iron can cause damage to and faillure of the heart and live, and diabetes. In a series of publications, CBR investigators Heather Leitch and Linda Vickars provide tantalizing data suggesting that reversing iron overload with “chelators” prolongs survival. These intriguing findings set the stage for large prospective trials and highlight the importance of understanding the intricate role of metals in health and disease. (Picture, courtesty of Dr. Deborah Griswold, show sideroblasts ringed with abnormal accumulations of iron.)

Myelodysplastic syndromes (MDS) and primary myelofibrosis (PMF) are bone marrow failure syndromes resulting in low blood cell counts and a heightened risk of developing acute myeloid leukemia. Although new specific treatments are becoming available, the mainstay of care for these patients is supportive, most frequently involving longterm, multiple transfusions with red blood cells. A predictable and inevitable side effect of chronic red cell transfusions is, however, iron overload. After a patient receives 10–20 units of red blood cells, the accumulated iron begins to cause damage to several organs, which may be manifest by irregular heart rhythms and heart failure, diabetes and liver failure. Fortunately, iron can be removed from the body – a process known as “chelation” – using a variety of medications that bind the iron and allow it to be excreted. Iron chelation is, however, not without potential serious side effects. It is therefore critical to weigh the risks and benefits before implementing such a therapeutic maneuver. The work of CBR scientists, Dr. Linda Vickars and Dr. Heather Leitch, has started to address one of the key questions, i.e. does lowering iron through chelation provide benefit in terms of survival for patients with MDS and PMF?

Drs. Leitch and Vickars are hematologists at St. Paul’s Hospital, Providence Health Care. Dr. Vickars is also the Director of the Iron Chelation (“Home Hemosiderosis”) Program for BC. These CBR investigators, with the help of UBC medical students Trisha Goodman and Karen Wong, led a retrospective review of 178 records of patients with MDS. Due to limited medications to treat MDS, most of the patients (126) received supportive care, i.e. mainly transfusions. Of those individuals who received iron chelation therapy, a significant reduction in iron, measured by serum ferritin, was achieved in 18 patients. Strikingly, the overall survival of patients who underwent chelation therapy was superior, with a 4-year survival of 64% versus 43% in non-chelation patients (p=0.003). In a subgroup analysis in which clinical features were matched in the chelation and non-chelation groups, the survival benefit for those receiving chelation therapy remained significant (p=0.01). These results have been confirmed in similar studies by other international groups. Moreover, the CBR group recently reported a survival benefit of iron chelation for primary myelofibrosis.

In spite of strong evidence supporting the value of iron chelation in these patients, the authors underline the fact that the studies so far have been retrospective in nature, and thus must be cautiously interpreted. Nonetheless, the findings are sufficiently exciting to have prompted multicenter prospective trials which are currently underway. As Dr. Barnett, Division Head of UBC Hematology, says, “This important work is particularly gratifying as it raises a number of intriguing questions ripe for collaborative research within the CBR and Division of Hematology.” Stay tuned!

Get the whole story in Hematol Oncol 2010; 28: 40–48
and Am Soc Hematol Educ Program. 2009:664-72.

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