Refractory anemia with ring sideroblasts: Epidemiological survival trends and implications in a SEER population-based study

Abstract Introduction: Refractory Anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome (MDS) subtype defined by anemia, dyserythropoiesis, and ≥15% ring sideroblasts in the bone marrow, driven largely by SF3B1 mutations and mitochondrial iron accumulation. It is largely seen as an indolent disease marked by transfusion-dependent anemia, fatigue, and progressive iron overload. Available therapies are limited beyond supportive care (e.g., erythropoietin, iron chelation) and the disease carries a low but real risk of progression to AML (~5–10%), contributing to substantial morbidity and mortality, especially in older adults. Available chemotherapies include luspatercept, hypomethylating agents like decitabine and azacitidine in more aggressive or refractory disease, and lenalidomide in del(5q) mutation co-ocurrence. This SEER database study aims to define real-world epidemiological factors and their prognostic implications in RARS, leveraging large-scale population data to address knowledge gaps and inform clinical decision-making. Objective and Methodology: A population-based analysis of RARS was performed using SEER Research Plus data (17 registries) from 2000 to 2022. A total of 5908 patients were identified using ICD 9982/3 code. Patients were classified by race, gender, therapy received, income, and age (<65 vs 65+). Kaplan-Meier curves were used to visualize differences in survival. Data was noted for significance based on standard and weighted (Gehan-Breslow-Wilcoxon) Log-Rank tests. Results: Of the 5908 patients, elderly patients (age 65+, 84.61%) had poorer outcomes, with a median survival of 51 months, compared to 103 months in patients under 65 (15.39%) with the significant P-value of <0.0001. Female gender (43.89%) was associated with slightly better median survival of 57 months vs 52 in males (56.11%) (P-Value <0.0001, weighted 0.0015). Patients receiving chemotherapy (11.27%) notably had worse outcomes with a median survival of 39 months compared to 56 months in patients not receiving chemotherapy (88.73%) (P-value <0.0001). Race and income could not show significant statistically significant correlation with a difference in outcome. Conclusion: Older patients had notably higher all-cause mortality, likely due to comorbidities as well as increased risk for malignant transformation. More notably, chemotherapy, on average, was associated with worse outcomes, likely reflecting patients with more aggressive disease compared to most untreated counterparts. There is no immediately clear explanation for the modest but significant survival advantage female gender provides. It is worth noting that, despite the indolent nature of the disease, its impact on the patient and the somewhat limited tools available for helping more aggressive cases remain a concern. Studies on risk stratification using next-generation sequencing exist, but further work is needed on early identification of patients at risk for worse disease and whether earlier treatment would improve outcomes.