Prognostic impact of elevated pretreatment serum ferritin in patients with high-risk MDS treated with azacitidine

Iron overload has been associated with poor overall survival in patients with higher-risk myelodysplastic syndromes after allogeneic hematopoietic stem cell transplantation, but has not been investigated in higher-risk MDS patients treated with hypomethylating agents. We evaluated the prognostic value of serum ferritin levels at diagnosis in a retrospective analysis of 48 patients with an intermediate 2 or high-risk International Prognostic Scoring System (IPSS) score treated with azacytidine. overall survival probability at 1 and 2 years was 58% and 42%, respectively. When stratifying according to serum ferritin level at azacytidine initiation, patients with serum ferritin level <725 ng/mL had significantly better OS than those with serum ferritin level ≥725 ng/mL, with an overall survival probability of 74% (95% confidence interval [CI]: 58-94) versus 44% (95% CI: 28-68) at 1 year and 57% (95% CI: 39-81) versus 28% (95% CI: 15-52) at 2 years, respectively (p = 0.034). Median progression-free survival was 16.15 months (range: 9-26) for the entire cohort. Progression-free survival probabilities according to serum ferritin cut-off level <725 ng/mL or ≥725 ng/mL at 1 and 2 years were 70% (95% CI: 53-91) versus 44 (95% CI: 28-68) and 52% (95% CI: 35-77) versus 24% (95% CI: 12-48), respectively (p = 0.031). We have demonstrated that an serum ferritin level ≥725 ng/mL was associated with worse overall survival and progression-free survival when adjusting for other covariables in multivariate analysis, in addition, unfavorable karyotype led to worse outcome. In conclusion, we believe that that negative effect of serum ferritin level on overall survival is not only related to the iron toxicity, but most probably may also be considered as a surrogate marker for very ineffective erythropoiesis leading to marked anemia.