自然杀伤细胞细胞毒性作为成人继发性噬血细胞性淋巴组织细胞增生症患者的诊断和预后标志物：一项前瞻性II期观察性研究。
Natural-killer cell cytotoxicity as a diagnostic and prognostic marker for adult patients with secondary hemophagocytic lymphohistiocytosis: a prospective phase II observational study.
作者信息
Oh Eun-Jee, Yoon Jae-Ho, Park Ki Hyun, Bae Hyun Joo, Yun So Jeong, Min Gi June, Park Sung-Soo, Park Silvia, Lee Sung-Eun, Cho Byung-Sik, Eom Ki-Seong, Kim Yoo-Jin, Lee Seok, Kim Hee-Je, Min Chang-Ki, Cho Seok-Goo, Han Kyungja, Lee Jong Wook
机构信息
Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Hematology, Catholic Hematology Hospital and Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
出版信息
Ther Adv Hematol. 2021 May 31;12:20406207211020544. doi: 10.1177/20406207211020544. eCollection 2021.
BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH) can be life-threatening if not detected and treated appropriately. The diagnosis of HLH can be confusing due to other similar febrile diseases that present with cytopenia. Natural-killer cell (NK)-cytotoxicity is an important diagnostic parameter for primary HLH; however, its role in secondary HLH in adults has not been well-elucidated.
METHODS
We prospectively enrolled 123 adult patients with febrile conditions accompanied by cytopenia or marrow hemophagocytosis. A diagnosis of HLH was based on HLH-2004 criteria and treated based on HLH-94 protocol. NK-cytotoxicity was calculated at the time of diagnosis by K562-cell direct lysis using flow-cytometry.
RESULTS
HLH ( = 60) was determined to be caused by Epstein-Barr virus (EBV) ( = 11), infection other than EBV ( = 16), malignancies ( = 19), and unknown ( = 14). Febrile diseases other than HLH ( = 63) were diagnosed as autoimmune disease ( = 22), malignancies ( = 21), infection ( = 12), non-malignant hematological diseases ( = 6), and unknown ( = 2). A lower NK-cytotoxicity level was observed at diagnosis in patients with HLH, compared with other causes of febrile disease (12.1% 26.2%, < 0.001). However, NK-cytotoxicity had a borderline effect on diagnosis of HLH, with an area under receiver operation characteristic curve of 0.689. It also showed no significant role for the prediction of survival outcome. Multivariate analysis revealed that malignant disease and high ferritin level were related with poor survival outcome. In non-malignant disease subgroups, old age, EBV-association, and low NK-cytotoxicity were related with poor survival.
CONCLUSIONS
Febrile disease with cytopenia was associated with decreased NK-cytotoxicity, especially in adults with HLH; however, its diagnostic role for adult HLH is still arguable. The diagnostic criteria for adult HLH should be further discussed.
TRIAL REGISTRATION
Clinical Research Information Service [Internet]; Osong (Chungcheongbuk-do), Korea, Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); https://cris.nih.go.kr/cris/index.jsp; Feb, 16th 2016; KCT0001886 (KC15TISE0936).
背景
噬血细胞性淋巴组织细胞增生症（HLH）若未得到及时诊断和恰当治疗，可能危及生命。由于其他伴有血细胞减少的发热性疾病与HLH表现相似，其诊断可能会造成混淆。自然杀伤细胞（NK）细胞毒性是原发性HLH的一项重要诊断参数；然而，其在成人继发性HLH中的作用尚未得到充分阐明。
方法
我们前瞻性纳入了123例伴有血细胞减少或骨髓噬血细胞现象的发热成人患者。HLH的诊断基于HLH-2004标准，并根据HLH-94方案进行治疗。诊断时通过流式细胞术检测K562细胞直接裂解来计算NK细胞毒性。
结果
确定HLH（n = 60）由爱泼斯坦-巴尔病毒（EBV）（n = 11）、EBV以外的感染（n = 16）、恶性肿瘤（n = 19）及病因不明（n = 14）引起。HLH以外的发热性疾病（n = 63）被诊断为自身免疫性疾病（n = 22）、恶性肿瘤（n = 21）、感染（n = 12）、非恶性血液病（n = 6）及病因不明（n = 2）。与其他发热性疾病病因相比，HLH患者诊断时观察到较低的NK细胞毒性水平（12.1% 对26.2%，P < 0.001）。然而，NK细胞毒性对HLH诊断的影响处于临界状态，受试者操作特征曲线下面积为0.689。其对生存结局的预测也未显示出显著作用。多因素分析显示，恶性疾病和高铁蛋白水平与不良生存结局相关。在非恶性疾病亚组中，高龄、EBV相关性及低NK细胞毒性与不良生存相关。
结论
伴有血细胞减少的发热性疾病与NK细胞毒性降低有关，尤其是成人HLH患者；然而，其对成人HLH的诊断作用仍存在争议。成人HLH的诊断标准应进一步探讨。
试验注册
临床研究信息服务[互联网]；韩国忠清北道峨山，疾病控制与预防中心，卫生与福利部（大韩民国）；https://cris.nih.go.kr/cris/index.jsp；2016年2月16日；KCT0001886（KC15TISE0936）
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