Prognostic Value of Serum Ferritin, Transferrin Saturation and C- Reactive Protein At Diagnosis In Myelodysplastic Syndrome Patients: Analysis of Patients From the MDS Piedmont Registry,

The prognostic role of serum ferritin (SF) evaluation at baseline in patients (pts) affected by myelodysplastic syndrome (MDS) is still controversial. In fact, increased SF mainly due to transfusion requirement during disease history has a clear negative impact on overall survival (OS) (Malcovati et al., 2006) and also on leukemic evolution (LE) (Sanz, ASH 2008, de Swart ASH 2010) while contrasting data about its role at baseline on OS has been published. Park and colleagues (ASH 2010) failed to identify a negative prognostic impact of SF higher than 300 ng/mL in a cohort of low risk untransfused MDS patients while data from the European LeukemiaNet MDS registry identified SF as an independent prognostic factor for OS and progression-free survival in low- and int-1 MDS (de Swart, Edimburgh 2011). SF can be a marker of iron overload but also of inflammation and little is known about the impact on survival of other iron parameters such as transferrin saturation (TS) or inflammation such as C reactive protein (CRP) in MDS pts at diagnosis. Aim: Aim of our study was to evaluate the prognostic role of iron parameters and inflammation at diagnosis in MDS patients analyzing data collected in the MDS Piedmont Registry. Materials and methods: 1360 patients enrolled in the MDS Piedmont Registry (1999–2010) were analyzed. Patients with information on OS and LE and available baseline SF (n=670), TS (n=299), CRP (n=287) were included in the analysis. Survival analysis was performed using Kaplan-Meier method. Patients were stratified according to a cut off value of 800 ng/mL for SF, 40% for TS and values within or higher the normal range (0,8 mg/dL) for CRP. In order to compare survival curves, log-rank test was used. Cumulative incidence of LE, according to SF, TS and CRP levels, was calculated accounting for death from any causes as a competing event. Results: In the population with SF baseline values, 3-years OS in pts with SF < 800 ng/mL was 80.7 (95%CI: 75.8–84.8) and in pts with SF >800 ng/mL was 66.1 (95%CI: 46.7–79.8) (p= 0,006). The result seems to be confirmed in the low risk MDS subgroup in toto (n=226) and considering only the untransfused pts (136 cases) (p=0,0073 and p=0,0038 respectively) but no statistically significance in OS of high risk pts (n=108) has been observed. In subjects with available data on TS, 3-years OS for pts with TS lower than 40% was 75.0 (95% CI: 64.2–83.0) while in pts higher than 40% was 72.1 (95%CI: 59.5–81.4) (p=0,1). Finally, in pts with CRP values 3-years OS was 80.8 (95%CI: 69.7–88.2) for patients < 0,8 mg/dL and 47.2 (95%CI: 34.5–58.9) for pts > 0,8 mg/dL. Also 3-year cumulative incidence of LE was higher in pts with SF > 800 ng/mL [35.8 (95%CI: 20.3–51.2) vs 18.5 (95%CI: 14.4–22.5); p=0,002 ] and in those with CPR > 0,8 mg/dL [35.3 (95%CI: 23.9–46.7) vs 12.7 (95%CI: 5.7–19.7); p<0,001]. In TS subgroups no difference was observed [13.5 (95%CI: 7.0–20.0) for TS<40% vs 20.8 (95%CI: 11.8–29.8) for TS>40%; p=0.172]. Conclusions: although the limits of missing data, our results suggest that high levels of SF and CRP above the normal range at baseline should have a prognostic role in MDS pts, while TS seems to have little impact on OS. Moreover SF and CRP seem to have both a negative impact on LE. Our data suggest a more important prognostic role of chronic inflammation parameters than iron overload or oxidative stress in MDS patients at diagnosis. Further prospective evaluation of more specific parameter of oxidative stress and inflammation need to be analyzed in order to confirm our preliminary observation.

No relevant conflicts of interest to declare.