【摘要】 目的:探讨宏基因二代测序(metagenomic next-generation sequencing, mNGS)技术在异基因造血干细胞移植后结核分枝杆菌(mycobacterium tuberculosis, MTB)感染中的应用。方法:收集2018年1月至2020年5月采用mNGS诊断的11例异基因造血干细胞移植后MTB感染患者的临床资料，回顾性分析患者的临床特征及治疗转归。结果:11例患者中男6例，女5例；中位年龄45(28～56)岁；结核类型主要为肺结核(9例，81.8%),另外结核性脑膜炎和结核菌血症各1例；移植后并发MTB感染的中位时间为4.1(1.1～12.1)个月。临床表现：以发热和呼吸道症状最常见，其中发热7例，呼吸道症状8例，1例结核性脑膜炎患者表现为发热、头痛和癫痫。实验室检查：11例患者中3例(27.3%)涂片抗酸染色阳性(2例肺泡灌洗液，1例脑脊液);9例(81.8%)外周血T-SPOT阳性；5例(45.5%)Xpert阳性(4例肺泡灌洗液，1例脑脊液);1例(9.1%)外周血MTB-PCR阳性。通过mNGS均检测出MTB序列数(1～154)。影像学表现：肺部CT表现为斑片状渗出影7例，纵隔旁团块影1例，多发粟粒状结节影1例，头颅MRI发现1例结核性脑膜炎患者大脑多发结节病灶。预后：经过积极治疗后9例患者获得MTB感染的治愈；1例患者MTB感染经积极治疗后未获得病情控制，死于肺部严重混合感染；另外1例患者死亡原因为MTB感染，总体治愈率为81.8%(9/11)。结论:mNGS技术可以明显提高异基因造血干细胞移植后MTB的检出率，为临床早期精准治疗提供重要的病原学依据。更多还原

【Abstract】 Objective: To explore the application of metagenomic next-generation sequencing(mNGS) technology in mycobacterium tuberculosis(MTB) infection after allogeneic hematopoietic stem cell transplantation. Methods: The clinical data of 11 patients with MTB infection after allogeneic hematopoietic stem cell transplantation diagnosed by mNGS from January 2018 to May 2020 were retrospectively analyzed. Results: Of the 11 patients, there were 6 males and 5 females. The median age was 45(28-56) years old. The main type of tuberculosis was pulmonary tuberculosis(9 cases, 81.8%). Other types included 1 case of tuberculous meningitis and 1 case of tuberculous bacteremia. The median duration of MTB presentation after transplantation was 4.1 months(range 1.1-12.1 months). The clinical manifestations were mainly fever and respiratory symptoms, including 7 cases of fever, 8 cases of respiratory symptoms, and 1 case of tuberculous meningitis with fever, headache and epilepsy. Laboratory examination: Three out of 11 patients(27.3%) showed positive acid-fast staining on smears(2 cases of bronchoalveolar lavage fluid and 1 case of cerebrospinal fluid); 9 cases(81.8%) were T-SPOT positive in peripheral blood; 5 cases(45.5%) were Xpert positive(4 cases of bronchoalveolar lavage fluid and 1 case of cerebrospinal fluid); 1 case(9.1%) had positive peripheral blood MTB-PCR. The MTB sequence number of all the patients were detected by mNGS(between 1-154). Image findings: The chest CT showed patched shadow in 7 cases, mass shadow near mediastinum in 1 case, multiple miliary nodular shadow in 1 case. Brain MRI revealed multiple nodular lesions in one patient with tuberculous meningitis. After active treatment, 9 patients were cured of MTB infection, and 1 patient died of severe mixed infection in the lungs without control, the other one died of MTB infection, with an overall cure rate of 81.8%(9/11). Conclusion: mNGS technology can significantly improve the detection rate of MTB after allogeneic hematopoietic stem cell transplantation, providing important pathogenic basis for early and precise clinical treatment.更多还原