Magnetic Resonance Imaging (MRI) Detection of Iron Overload In Patients with Myelodysplastic Syndrome (MDS),

Transfusion dependent anemia and iron overload (IO) are associated with reduced survival in MDS. Serum ferritin is the most common method of assessing body iron content, but is also an inflammatory marker, and may not correlate with IO in specific organs. T2* magnetic resonance imaging (MRI) is a non-invasive method for detecting IO. The prevalence of IO in patients with MDS, as detected by T2* MRI, is currently unknown. Purpose: We designed a single center trial to evaluate the efficacy of T2* MRI in detection of IO in patients with MDS, determine the prevalence of iron overload in this disease and correlate MRI findings with iron indexes (ferritin, transferrin and labile plasma iron [LPI]). Material and methods: Patients with WHO-2008 defined MDS or chronic myelomonocytic leukemia (CMML), independent of transfusion requirements, were eligible. Patients receiving iron chelation therapy were excluded. Iron indexes were measured at the time of T2* MRI evaluation. Hepatic iron overload (HIO) was considered in patients with a hepatic iron concentration (HIC) ≥ 2 g/mg. Cardiac iron overload (CIO) was considered in patients with a T2* value < 20 milliseconds. Results: A total of 58 patients with MDS and two patients with CMML have been recruited. Three patients were not evaluated by MRI due to claustrophobia, so 57 patients remain for the analysis. Median age was 66 years (range 18–89). MDS subtypes by WHO included: refractory anemia (N=5), refractory anemia with ring sideroblasts (RARS; N=7), 5q- syndrome (N=4), refractory cytopenias with multilineage dysplasia (N=21), refractory anemia with excess blasts-I (N=7) and –II (N=7), unclassifiable MDS (N=3), CMML (N=2) and therapy-related MDS (N=1). Clinical features at time of MRI are presented in table 1. Median cardiac T2* value was 42 ms (range 19.7–70.1 ms), and only one patient had a T2* value indicative of CIO. Median HIC value was 3.9 g/mg (range 0.9–16 g/mg), and 68% of patients had HIO. Patients with HIO had higher ferritin levels (1182 ng/mL vs. 185 ng/mL, p<0.0001) and transferrin saturation (76% vs. 34%, p<0.0001), but no difference in LPI (0.13 vs. 0.12 mM, p=0.49). HIO was found in 76% of transfusion dependent patients, but in also 59% of patients without history of transfusions. Among patients with HIO but without a history of transfusions, 50% had RARS. Considering MRI as a gold standard for detecting HIO, a ferritin value ≥ 1.000 ng/ml had a positive predictive value (PPV) for HIO of 98% and a NPV of 48%; for transferrin saturation ≥ 50%, PPV was 91% and NPV was 55%. Conclusions: This is one of the largest studies evaluating IO in MDS by T2* MRI. The prevalence of iron overload in MDS is underestimated by using conventional iron indexes and T2* MRI can help in the early detection of IO. In some subtypes of MDS, such as RARS, mechanisms other than transfusion dependency lead to IO.

Santos:Janssen-Cilag: Consultancy, Speakers Bureau; United Medical: Consultancy, Speakers Bureau; Novartis: Research Funding. Hamerschlak:Novartis: Research Funding.