Liu Yanping, Ren Yimin, Gao Ling, Ahmed Shanza, Lu Xuzhang, Li Bingzong, Wang Chunling, Yu Liang, Sun Miao, Zhuang Yun, Miao Yuqing, Ni Haiwen, Xie Xiaoyan, Shi Xiaofeng, Xu Jingyan, Zhang Yunping, Zhao Min, Xu Min, Zhuang Wanchuan, Gu Weiying, Lin Guoqiang, Hua Haiying, Zhu Jianfeng, Xu Maozhong, Jia Tao, Liu Ping, Zhai Lijia, Zhang Tongtong, Shan Huirong, Shen Qiudan, Fan Lei, Li Jianyong, Shi Wenyu, Miao Yi
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
Jiangsu Cooperative Lymphoma Group (JCLG) and Jiangsu Histiocytosis Association Lymphoma Group, Nanjing Medical University, Nanjing, China.
Am J Hematol. 2025 Nov;100(11):2052-2063. doi: 10.1002/ajh.70063. Epub 2025 Sep 8.
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.
淋巴瘤相关噬血细胞性淋巴组织细胞增生症（LA-HLH）是一种危及生命的高炎症综合征，基于预后模型的分层管理很重要。内皮激活和应激指数（EASIX）评分已在异基因干细胞移植受者和嵌合抗原受体（CAR）T细胞治疗中显示出预后效用。然而，其在LA-HLH中的作用尚未明确。我们对来自28个医学中心的LA-HLH患者进行了多中心回顾性分析，以探讨EASIX对LA-HLH的预后影响。EASIX通过基线乳酸脱氢酶、血清肌酐和血小板计数计算得出。共纳入490例LA-HLH患者，并根据EASIX四分位数（Q1-Q4）进行分层。根据Kaplan-Meier分析，EASIX评分较高的患者2个月生存率和总生存率显著较低（对数秩p<0.001）。在多变量分析中，在调整年龄、性别、淋巴瘤类型、脾肿大、骨髓浸润、淋巴瘤状态（初治与复发/难治）、血红蛋白、绝对中性粒细胞计数、血清铁蛋白水平和天冬氨酸转氨酶后，最高EASIX四分位数（Q4）与最低四分位数（Q1）相比，死亡风险高7.01倍（风险比[HR]=7.01，95%置信区间[CI]：3.98-12.36；p<0.001）。此外，受限立方样条（RCS）分析表明，随着EASIX评分增加，死亡风险增加。我们的研究结果支持EASIX作为LA-HLH的一个强大、普遍可用的预后标志物，与早期死亡风险密切相关。该指数可用于对LA-HLH患者的风险水平进行分层并预测其生存结果。
