Iron overload may promote alteration of NK cells and hematopoietic stem/progenitor cells by JNK and P38 pathway in myelodysplastic syndromes.
BACKGROUND Iron chelation therapy (CT) improves survival in thalassemia major but its beneficial effects on survival in MDS patients remain uncertain. METHODS We analyzed, by multivariate analysis, survival and causes of deaths in 97 low or intermediate 1 IPSS patients regularly transfused as outpatients, chelated or not, who were included during a month period and followed for 2.5 years. RESULTS 44 (45%) of patients were not chelated and 53 (55%) received CT, mainly with deferoxamine, for at least 6 months (median duration of chelation 36 months, range 6-131+). During the follow-up period, 66 of the 97 patients died, including 51% and 73% of chelated and non-chelated patients, respectively. Median overall survival was 53 months and 124 months in non-chelated and in chelated patients (p<0.0003). Causes of death did not significantly differ between the two groups (p=0.51). In multivariate Cox analysis, adequate chelation was the strongest independent factor associated with better OS. CONCLUSION Iron chelation therapy appears to improve survival in heavily transfused lower risk MDS, but prospective randomized studies are required to confirm our findings, and to determine more precisely the mechanisms of this potential survival benefit.