Endothelial Activation and Stress Index Serves as a Predictor for Survival in Lymphoma‐Associated Hemophagocytic Lymphohistiocytosis: A Retrospective Multicenter Cohort Study of Jiangsu Cooperative Lymphoma Group

ABSTRACT Lymphoma‐associated hemophagocytic lymphohistiocytosis (LA‐HLH) is a life‐threatening hyperinflammatory syndrome, and hierarchical management based on a prognostic model is important. The endothelial activation and stress index (EASIX) score has demonstrated prognostic utility in recipients of allogeneic stem cell transplantation and chimeric antigen receptor (CAR) T‐cell therapy. However, its role in LA‐HLH remains unestablished. We conducted a multicenter retrospective analysis of patients with LA‐HLH from 28 medical centers to explore the prognostic impacts of EASIX in LA‐HLH. EASIX was calculated using baseline lactate dehydrogenase, serum creatinine, and platelet counts. A total of 490 patients with LA‐HLH were included and stratified by EASIX quartiles (Q1–Q4). Patients with a higher EASIX score had significantly inferior 2‐month survival and overall survival, according to the Kaplan–Meier analysis (log‐rank p < 0.001). In multivariable analyses, after adjustment for age, gender, lymphoma type, splenomegaly, bone marrow infiltration, lymphoma status (treatment‐naïve versus relapsed/refractory), hemoglobin, absolute neutrophil count, serum ferritin levels, and aspartate aminotransferase, the highest EASIX quartile (Q4) exhibited a 7.01‐fold risk of death compared to the lowest quartile (Q1) (Hazard ratio [HR] = 7.01, 95% confidence interval [CI]: 3.98–12.36; p < 0.001). Additionally, the restricted cubic splines (RCS) analysis illustrated an increase in the risk of mortality with an increasing EASIX score. Our findings support EASIX being a robust, universally accessible prognostic marker for LA‐HLH, strongly associated with early mortality risk. This index can be used to stratify the risk levels of patients with LA‐HLH and predict their survival outcomes.