噬血细胞综合征患者早期死亡危险因素的临床分析

Clinical analysis of risk factors for early death in patients with hemophagocytic lymphohistiocytosis

目的:分析噬血细胞性淋巴组织细胞增生症(hemophagocytic lymphohistiocytosis,HLH)早期死亡患者的临床特征,探讨影响HLH患者早期死亡的可能危险因素,以期识别早期死亡风险高的患者。方法:回顾性分析2015年6月—2022年6月徐州医科大学附属医院收治的102例HLH患者的临床资料。根据是否于诊断后30 d内死亡,分为早期死亡组和早期存活组,比较2组患者的临床特征,应用Cox回归模型分析HLH患者早期死亡的独立危险因素。结果:102例HLH患者发生早期死亡38例,早期死亡率为37.3%,早期死亡患者的中位生存时间为11(2~30)d。对早期死亡患者与早期存活患者的临床特征进行分析,2组间在血小板计数(PLT)、白蛋白、预后营养指数、纤维蛋白原、乳酸脱氢酶、血钙(Ca^(2+))、是否发生深部器官出血、是否累及神经系统及治疗2周有无反应比较,差异有统计学意义(P<0.05)。多因素Cox回归分析显示:PLT≤44×10^(9)/L(HR=0.346,95%CI 0.148~0.808,P=0.014)、预后营养指数≤30.95(HR=0.254,95%CI 0.083~0.774,P=0.016)、Ca^(2+)≤1.73 mmol/L(HR=0.448,95%CI 0.225~0.891,P=0.022)、神经系统累及(HR=0.402,95%CI 0.177~0.915,P=0.030)及治疗2周无反应(HR=0.367,95%CI 0.140~0.958,P=0.041)是HLH患者早期死亡的独立危险因素。进一步按照危险因素的数量对HLH患者进行风险分层,低危组50例,中危组40例和高危组12例,3组患者30 d生存率分别为84.0%、47.5%和8.3%。与低危组患者比较,中危及高危组患者的早期死亡风险分别增加了14.8倍和48.1倍(P<0.01)。结论:HLH早期死亡与多种因素相关,早期神经系统受累、PLT≤44×10^(9)/L、预后营养指数≤30.95、Ca^(2+)≤1.73 mmol/L和治疗2周无反应是HLH患者早期死亡的独立危险因素;风险分层有助于识别高危患者,及时调整治疗策略从而降低早期死亡率。

Objective To analyze the clinical characteristics of early death patients with hemophagocytic lymphohistiocytosis(HLH),and to explore the possible risk factors affecting early death of HLH patients,in order to identify patients with high risk of early death.Methods The clinical data of 102 patients with HLH admitted to the Affiliated Hospital of Xuzhou Medical University from June 2015 to June 2022 were retrospectively analyzed.According to whether the patients died within 30 days after diagnosis,they were divided into early death group and early survival group.The clinical characteristics of the two groups were compared,and the independent risk factors of early death of HLH patients were analyzed by Cox regression model.Results Among 102 patients with HLH,38 cases died early,the early mortality was 37.3%,and the median survival time of early death patients was 11(2-30)days.The clinical characteristics of early death patients and early survival patients were analyzed,and the differences between the two groups were statistically significant in platelet count,albumin,prognostic nutritional index,fibrinogen,lactate dehydrogenase,blood calcium,whether deep organ bleeding occurred,whether nervous system was involved,and whether there was reaction after 2 weeks of treatment(P<0.05).Multi-factor Cox regression analysis showed that platelet≤44×10^(9);L(HR=0.346,95%CI 0.148-0.808,P=0.014),prognostic nutrition index≤30.95(HR=0.254,95%CI 0.083-0.774,P=0.016),blood calcium≤1.73 mmol;L(HR=0.448,95%CI 0.225-0.891,P=0.022),nervous system involvement(HR=0.402,95%CI 0.177-0.915,P=0.030)and no response after 2 weeks of treatment(HR=0.367,95%CI 0.140-0.958,P=0.041)were independent risk factors for early death in patients with HLH.According to the number of risk factors,the patients with HLH were further risk stratified,with 50 patients in the low-risk group,40 patients in the medium-risk group and 12 patients in the high-risk group.The 30-day survival rates of the three groups were 84.0%,47.5%and 8.3%,respectively.Compared with the low-risk group,the risk of early death in the medium-risk and high-risk group was 14.8 and 48.1 times higher,respectively(P<0.01).Conclusion The early death of HLH patients is related to various factors.Early neurological involvement,platelet≤44×10^(9);L,prognostic nutrient index≤30.95,blood calcium≤1.73 mmol;L and non-response for 2 weeks of treatment are independent risk factors for early death of HLH patients.Risk stratification is helpful to identify high-risk patients and timely adjust treatment strategies to reduce early mortality.