Among transfusion-dependent patients with a lower-risk myelodysplastic syndrome (LRMDS) subtype with ring sideroblasts, the risks of iron toxicity appear to be higher than in other MDS subtypes, according to research published in Leukemia.

Patients with LRMDS are often treated with red blood cell transfusions (RBCTs), although dependence on transfusion is linked to worse overall outcomes. Frequent RBCT may also be linked to iron toxicity, which is a negative prognostic variable in this patient population.

While many aspects of iron metabolism in LRMDS are not yet established, hepcidin, a peptide hormone, is known to play a key role in iron uptake inhibition. High levels of reactive oxygen species (ROS) are also linked with both iron toxicity and MDS progression, though the direct effects of ROS on disease progression are also unknown. For this study, researchers evaluated data from patients with LRMDS to determine markers of iron and oxidative stress, and to evaluate any relationships between these factors and survival.

Overall, data from 256 patients were included. Most (169 patients; 66.0%) patients were men, 118 (46.1%) patients were aged 75 years or older, the majority (195 patients; 76.2%) had a revised International Prognostic Scoring System rating of very low/low risk, and 158 (61.7%) patients had a low-risk comorbidity index score. Patients were grouped into 1 of 4 classes: nonring sideroblast transfusion-independent (143 patients; 55.9%), nonring sideroblasts transfusion-dependent (47 patients; 18.4%), ring sideroblast transfusion-independent (48 patients; 18.8%), and ring sideroblast transfusion dependent (18 patients; 7.0%).


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The median follow-up period was 6.6 years. The median overall survival was 4.8 years (95% CI, 3.9-not reached). Of the reported deaths, 15 (34.1%) were not MDS-related, 24 (54.5%) were MDS-related, and 5 (11.4%) were of unknown cause.

Among patients who were transfusion-dependent, of the characteristics investigated, labile plasma iron (LPI) was linked with worse overall survival (adjusted hazard ratio for LPI scores greater than the lower limit of detection, 2.7; P =.001). Worse OS was also noted for transfusion-independent patients where LPI was greater than the lower limit of detection (adjusted hazard ratio, 4.5; P =.01). Patients who were transfusion-dependent and who had ring sideroblasts also had worse survival compared with the other evaluated groups.

“In conclusion, iron toxicity is associated with inferior survival in LRMDS patients,” the authors wrote. “More restrictive RBCT strategies and pre-emptive iron reducing interventions may prevent or reverse these unwanted effects.”

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Hoeks M, Bagguley T, van Marrewijk C, et al. Toxic iron species in lower-risk myelodysplastic syndrome patients: course of disease and effects on outcome. Leukemia. Published online September 18, 2020. doi:10.1038/s41375-020-01022-2