Downregulation of IL-6–induced STAT3 phosphorylation in CD4⁺FOXP3⁻Tcons after AZA correlates significantly with better response and survival of HR-MDS patients. Kaplan-Meier curves for OS (A) and EFS (B) in HR-MDS patients who down- or upregulated the IL-6/STAT3 node in Tcons. Median OS of downregulators of IL-6/STAT3 (n = 28) was 27.2 months (95% confidence interval [CI]: 15-39.4) compared with 11.2 months (95% CI: 9.1-13) for upregulators (n = 26) (hazard ratio [HR]: 0.41, 95% CI: 0.22-0.78, P = .006). Median EFS of downregulators of IL-6/STAT3 was 16.6 months (95% CI: 8.1-25) compared with 9.45 months (95% CI: 7.55-11.05)] for upregulators (HR: 0.47, 95% CI: 0.25-0.86, P = .015). (C-D) Likewise, IL-6/STAT3 downregulators displayed significantly higher response rates (C), whereas no differences were noted between the 2 groups regarding World Health Organization subtype, cytogenetics according to IPSS-R and IPSS-R category, and transfusion intensity (D). (E) Forest plot of univariate analysis of predictive factors for OS. Upregulation of the IL-6/STAT3 node in Tcons was the only significant parameter in multivariate analysis. IPSS-R, Revised International Prognostic Scoring System.