Improved survival in patients with myelodysplastic syndromes receiving iron chelation

The myelodysplastic syndromes ( MDS ) are a group of diseases in which the bone marrow loses its ability to produce enough normal blood cells, and many patients with MDS experience anemia . However, repeated transfusions may cause dangerous iron overload in some patients, as can the underlying MDS itself. Patients with MDS and iron overload can receive iron chelation therapy ( ICT ), which helps prevent iron-related cell damage, although there are no studies to date that relate ICT to improved clinical outcome.

To determine the effect of iron chelation on patients with MDS and iron overload, researchers from the University of British Columbia performed a retrospective review of 178 MDS patients treated at St. Paul’s Hospital in Vancouver, British Columbia.

Clinical data were collected and evaluated from the Iron Chelation Program of British Columbia database. Using the International Prognostic Scoring System ( IPSS ), which predicts survival and risk of transformation to acute myeloid leukemia ( AML ), investigators predicted the course of MDS in 133 patients and classified the disease risk as low ( 44 patients ), intermediate-1 ( 55 patients ), intermediate-2 ( 17 patients ), or high ( 17 patients ).

A total of 18 patients with low or intermediate-1 risk IPSS were eligible for ICT due to elevated ferritin levels ( 13 patients ), clinical and biochemical evidence of iron overload ( 3 patients ), or number of transfusions received ( 2 patients ).
These patients were treated with a chelating agent, Desferroxamine ( Desferal; 0.5-3 grams), through subcutaneous infusion over 12 hours, five days per week (median duration, 15 months).

Researchers noted that ICT patients generally showed higher initial ferritin levels ( median 4,215 ug/L ) and significantly lower post-ICT ferritin levels ( median 2,659 ug/L ), as compared to ferritin levels in non-ICT patients ( median 1,647 and 3,188 ug/L, respectively ).

Documented causes of death ( n=71 ) in non-ICT patients were AML ( 22 patients ), MDS-related ( 21 patients ), infection/sepsis ( 18 patients ), and non-MDS-related ( 10 patients ).
Only three deaths – from acute myeloid leukemia , MDS complications, and iron overload – were documented among the ICT patients.

The median overall survival for patients in the study was 36 months.
Median overall survival was more than 160 months in patients with low or intermediate-1 IPSS receiving ICT, compared to 40.1 months for non-ICT patients. Importantly, the four-year survival rate of patients who received ICT was 80 percent, compared to only 44 percent among non-ICT patients.

“ 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, ” said Heather A. Leitch, at University of British Columbia, Vancouver.

Source: American Society of Hematology ( ASH ) – Annual Meeting, 2006


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