Abstract
Background: Most experts agree that iron chelation therapy is unlikely to benefit myelodysplastic syndrome (MDS) patients with a bone marrow (BM) blast percentage of ≥ 5% because of the associated short life expectancy. In contrast, using a serum ferritin of 1,000 ng/mL as a surrogate for iron overload, a recent study suggested a negative impact of iron overload on overall survival in MDS patients with < 5% BM blasts including those with refractory anemia with ringed sideroblasts (RARS) (Malcovati et al. JCO2005:23:7594). In the current retrospective study, we examined the validity of this observation in a large group of RARS patients seen at a single institution.
Methods: The diagnosis of RARS was based on the French-American-British cooperative group criteria. Serum ferritin levels obtained both at diagnosis and during follow-up as well as total number of packed red blood cells transfused were recorded. Standard statistical methods were used for survival and other analyses.
Results: A total of 126 RARS patients (median age 73 years, range 44-90; 67% males) were seen at our institution over the last several years. At diagnosis, median (range) values were 9.4 g/dL (5.7-13.4) for hemoglobin (Hgb), 2.8 × 109/L (0.3-13.7) for absolute neutrophil count (ANC) and 214× 109/L (22-819) for platelet count; 38% of the patients had received red blood cell (RBC) transfusions at the time of initial diagnosis. International Prognostic Scoring System (IPSS) risk distributions in evaluable patients were 66% for low, 28% for intermediate-1 and 6% for intermediate-2 risk. Median follow-up was 36 months and during this time 83 patients (66%) had died and leukemic transformation was documented antemortem in 8 patients (6%). As expected, IPSS was highly predictive of survival outcome (p<0.0001). In addition, history of RBC transfusions at diagnosis (p=0.001) but not the total number of RBC transfusions received during the entire disease course (p=0.17) carried an independent prognostic value for inferior survival. There were no significant correlations between overall survival and serum ferritin level at either diagnosis (median 567 ng/mL, range 16-3,475; p=0.24) or the maximum value during follow-up (median 1,108 ng/mL; range 238-43,500; p=0.72). Similarly, Kaplan-Meier plots of 77 evaluable patients stratified by serum ferritin levels of < or ≥1000 ng/mL at diagnosis or 107 evaluable patients stratified by maximal serum ferritin levels of < 1000, 1000-5000, or > 5000 ng/mL during follow-up revealed similar curves (Figure).
Conclusions: The current study suggests no significant association between transfusional hemosiderosis and survival even in good risk patients with MDS. The study also undermines the utility of serum ferritin as a surrogate for assessing the value of therapeutic iron chelation.
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