免疫检查点抑制剂致噬血细胞性淋巴组织细胞增生症文献病例分析  

Literature case analysis of hemophagocytic lymphohistiocytosis due to immune checkpoint inhibitors

作　　者：荆申奥 邱胜男 李呈好 黄欣[1] Jing Shen'ao;Qiu Shengnan;Li Chenghao;Huang Xin(Department of Pharmacy,the First Affiliated Hospital of Shandong First Medical University(Shandong Provincial Qianfoshan Hospital),Ji′nan 250014,China;School of Pharmacy,Shandong University of Traditional Chinese Medicine,Ji′nan 250355,China;School of Pharmacy,Shandong University,Ji′nan 250012,China)

机构地区：[1]山东第一医科大学第一附属医院(山东省千佛山医院)药学部,济南250014 [2]山东中医药大学药学院,济南250355 [3]山东大学药学院,济南250012

出　　处：《药物不良反应杂志》2024年第8期480-486,共7页Adverse Drug Reactions Journal

摘　　要：目的了解免疫检查点抑制剂(ICI)相关噬血细胞性淋巴组织细胞增生症(HLH)的临床特点。方法检索国内外有关数据库(截至2024年2月15日),收集ICI致HLH的病例报告,提取相关资料(性别、年龄、原患疾病、ICI用法用量、联合用药、HLH发生时间与临床表现、临床处理及转归等),进行描述性统计分析。结果共纳入37篇病例报告,涉及44例患者,男性26例,女性18例;年龄2~86岁,中位年龄67岁。原患疾病为黑色素瘤14例,肺癌12例,肾癌4例,口咽鳞状细胞癌2例,急性髓系白血病2例,其他10种恶性肿瘤各1例。共使用8种ICI类药物,帕博利珠单抗17例,纳武利尤单抗10例,纳武利尤单抗联合伊匹木单抗8例,阿替利珠单抗、卡瑞利珠单抗、伊匹木单抗各2例,特瑞普利单抗、替雷利珠单抗和阿维鲁单抗各1例。33例患者接受ICI单药治疗,6例接受免疫治疗联合靶向治疗,5例接受免疫治疗联合化疗;22例有用药剂量记录,给药方式均为静脉滴注。HLH发生时间最短为用药后1 d,最长为用药后8个月,中位时间5 d。患者临床表现为反复发热、疲劳、食欲不振等,实验室检查和辅助检查显示血细胞减少、铁蛋白升高以及噬血细胞增多和脾脏肿大。诊断HLH后,40例停药,1例未停药,3例不详;42例患者接受对症治疗,其中18例恢复正常,17例症状改善,6例死亡,1例预后不详;2例未进行干预者均死亡。结论ICI相关HLH的主要临床表现为发热、疲劳、食欲下降和噬血细胞增多。停药并对症治疗可有效改善患者症状,但HLH有较高的死亡风险。Objective To understand the clinical characteristics of hemophagocytic lymphohistiocytosis(HLH)induced by immune checkpoint inhibitors(ICIs).Methods Relevant databases at home and abroad(up to February 15,2024)were searched and case reports of HLH induced by ICIs were collected.Relevant information of patients(gender,age,primary disease),usage and dosage of ICI,combined drugs,occurrence time,clinical manifestations,management,and outcomes of HLH were extracted and analyzed descriptively and statistically.Results A total of 37 case reports were enrolled in the analysis,involving 44 patients.Of them,26 patients were male and 18 were female.The age ranged from 2 to 86 years,with a median age of 67 years.The primary diseases included melanoma in 14 patients,lung cancer in 12 patients,kidney cancer in 4 patients,oral squamous cell carcinoma and acute myeloid leukemia in 2 patients each,and other 10 malignant tumors in one patient each.A total of 8 ICIs were used,including pembrolizumab in 17 patients,nivolumab in 10 patients,nivolumab combined with ipilimumab in 8 patients,atezolizumab,camrelizumab,and ipilimumab in 2 patients each,and toripalimab,tislelizumab,and avelumab in 1 patient each.Among them,33 patients received single ICI immunotherapy,6 patients received immunotherapy combined with targeted therapy,and 5 patients received immunotherapy combined with chemotherapy.Twenty-two patients had medication dosage records,and the administration method was all intravenous infusion.The shortest time for HLH occurrence was 1 day after medication,the longest was 8 months,and the median time was 5 days.The clinical manifestations included recurrent fever,fatigue,loss of appetite,etc.Laboratory and auxiliary examinations showed decreased blood cells,elevated ferritin,increased hemophagocytic cells,and spleen enlargement.After the diagnosis of HLH,40 cases discontinued the drug,1 did not stop,and 3 were unknown.Forty-two patients received symptomatic treatments,of which 18 patients returned to normal,17 patients were improv

关 键 词：免疫检查点抑制剂 淋巴组织细胞增生症 噬血细胞性 血细胞计数 骨髓检查 铁蛋白质类 药物相关副作用和不良反应 

分 类 号：R979.1[医药卫生—药品]