Iron chelation therapy may improve overall survival in patients with MDS

Those not treated for iron overload could succumb to leukemia or sepsis.

Issue: January 1, 2007

Iron-chelation therapy, with deferoxamine, could improve survival in patients with bone-marrow disorders who experience iron overload resulting from red blood transfusion according to research presented at the 48th Annual Meeting of the American Society of Hematology.

In patients with myelodysplastic syndrome (MDS), the bone marrow loses its ability to produce enough normal blood cells, which could result in anemia. Blood transfusions are needed to manage the anemia, however, they can lead to dangerous levels of iron in the blood. The iron overload threatens major organ systems, making the excess iron at least as life-threatening as the underlying MDS, according to Heather A. Leitch, MD, PhD, clinical assistant professor at the University of British Columbia in Vancouver.

To prevent iron-related organ damage, patients with MDS may receive iron chelation therapy (ICT) so they can continue blood transfusions. Iron-chelating agents, such as deferoxamine, bind to the excess iron, and are excreted in the urine with the iron.

Leitch and colleagues analyzed the survival rates of patients with MDS who were receiving ICT. They performed a retrospective study of data from 178 patients treated between January 1981 and April 2006 at St. Paul’s Hospital in Vancouver, British Columbia.

A group of 18 patients with elevated levels of iron, determined by tests of levels of ferritin, were chosen to receive ICT. The median length of treatment was 15 months. Treatment consisted of subcutaneous infusion of 0.5 g to 3 g of deferoxamine 12 hours a day for 5 days a week.

The median overall survival rate of those receiving ICT was 160 months, compared with a median survival rate of 40 months for those who did not receive ICT. The four-year survival for those who received ICT was 80%. Among non-ICT patients, only 44% achieved four-year survival.

The most prevalent cause of death among non-ICT patients was acute leukemia, followed by MDS-related causes, infection or sepsis, and non-MDS-related causes.

“Although we were not able to demonstrate a decrease in organ dysfunction in patients receiving iron-chelation therapy for MDS, there was a significant improvement in overall survival,” Leitch said in a statement.

“To our knowledge, these are the first data documenting improvement in clinical outcome in patients with MDS receiving iron-chelation therapy, and we hope to confirm the results in a prospective study,” she said. – by Guy Burdick

Editor’s note: The decreased incidence of leukemia in iron-chelated patients suggests a role for iron-catalyzed oxidation of DNA that might hasten oncogenic mutations. The recent availability of new oral iron-chelating drugs may make chelation therapy more tolerable and should lead to further trials of this kind. – Harry S. Jacob, MD, FRCPath(Hon)

For more information:
Leitch, HA, Goodman, TA, Wong, KK, et al. Improved survival in patients with myelodysplastic syndrome (MDS) receiving iron chelation therapy. Presented at: the 48th Annual Meeting of the American Society of Hematology, Dec. 9-12, 2006. Orlando, Fla.