Time-Dependent Prognostic Value of the mEASIX Score in Patients with Myelodysplastic Syndromes

Background/Objectives: The modified Endothelial Activation and Stress Index (mEASIX), derived from routinely available laboratory parameters, has emerged as a potential biomarker reflecting systemic inflammatory and endothelial stress. However, its prognostic value in myelodysplastic syndromes (MDS) remains incompletely defined. This study evaluated the association between the mEASIX and overall survival and explored its time-dependent prognostic pattern. Methods: This retrospective study included 151 patients with MDS. The mEASIX score was calculated using C-reactive protein, lactate dehydrogenase, and platelet count and was log-transformed for regression analyses. Overall survival was estimated using the Kaplan-Meier method. Univariable and multivariable Cox proportional hazards models were used to evaluate prognostic factors, including age, IPSS-R risk group, hypomethylating agent (HMA) exposure, and venetoclax exposure. The proportional hazards assumption was assessed, and landmark analyses were performed at the median follow-up time (29 months). Receiver operating characteristic analysis was used to determine the optimal mEASIX cut-off value for mortality prediction. Model comparison, internal validation, and sensitivity analyses were also performed. Results: During a median follow-up of 29 months, 85 deaths occurred. The mEASIX yielded an AUC of 0.767 for mortality prediction (95% CI 0.691-0.844; p < 0.001). Patients with a high mEASIX had inferior overall survival (log-rank p < 0.001). In multivariable Cox regression analysis including age, IPSS-R risk group, HMA exposure, and venetoclax exposure, log(mEASIX) remained independently associated with inferior overall survival (HR 1.325, 95% CI 1.166-1.506; p < 0.001). In landmark analyses, this association persisted during the early follow-up period (≤29 months; HR 1.347, 95% CI 1.172-1.548; p < 0.001) but was attenuated during the late period (>29 months; HR 1.287, 95% CI 0.930-1.782; p = 0.128). Conclusions: The baseline mEASIX was independently associated with overall survival in patients with MDS and appeared most prognostically relevant during early follow-up. These findings suggest that the mEASIX may complement established risk models, although further validation is needed before broader clinical use.