应用宏基因组二代测序诊断异基因造血干细胞移植后早期侵袭性真菌病患者的临床分析

姬玉涵; 潘明月; 来晓瑜; 刘丽珍; 施继敏; 赵妍敏; 余建; 杨露欣; 罗依

doi:10.16016/j.2097-0927.202310087

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应用宏基因组二代测序诊断异基因造血干细胞移植后早期侵袭性真菌病患者的临床分析

专题报道：血液肿瘤诊治前沿 | 更新时间：2026-01-09

- 应用宏基因组二代测序诊断异基因造血干细胞移植后早期侵袭性真菌病患者的临床分析
- Clinical analysis of metagenome next-generation sequencing for diagnosing invasive fungal disease in patients with early stage of hematopoietic stem cell transplantation
- 陆军军医大学学报 2024年46卷第4期页码：311-318
- 作者机构：
  
  1.310000 杭州，浙江大学医学院附属第一医院骨髓移植中心
  2.473000 南阳，南阳市第二人民医院血液内科
- 作者简介：
  
  [罗依，E-mail: luoyijr@zju.edu.cnLUO Yi, E-mail: luoyijr@zju.edu.cn
- 基金信息：
- DOI：10.16016/j.2097-0927.202310087
  中图分类号： R446.9;R519.04;R552.05
- 收稿：2023-10-23，
  
  修回：2023-12-26，
  
  纸质出版：2024-02-28
- 稿件说明：
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姬玉涵, 潘明月, 来晓瑜, 等. 应用宏基因组二代测序诊断异基因造血干细胞移植后早期侵袭性真菌病患者的临床分析[J]. 陆军军医大学学报, 2024,46(4):311-318.

Yuhan JI, Mingyue PAN, Xiaoyu LAI, et al. Clinical analysis of metagenome next-generation sequencing for diagnosing invasive fungal disease in patients with early stage of hematopoietic stem cell transplantation[J]. Journal of Army Medical University, 2024, 46(4): 311-318.
姬玉涵, 潘明月, 来晓瑜, 等. 应用宏基因组二代测序诊断异基因造血干细胞移植后早期侵袭性真菌病患者的临床分析[J]. 陆军军医大学学报, 2024,46(4):311-318. DOI： 10.16016/j.2097-0927.202310087.

Yuhan JI, Mingyue PAN, Xiaoyu LAI, et al. Clinical analysis of metagenome next-generation sequencing for diagnosing invasive fungal disease in patients with early stage of hematopoietic stem cell transplantation[J]. Journal of Army Medical University, 2024, 46(4): 311-318. DOI： 10.16016/j.2097-0927.202310087.

摘要

目的

分析异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation

allo-HSCT)后早期应用宏基因组二代测序(metagenomic next-generation sequencing

mNGS)诊断侵袭性真菌病(invasive fungal disease

IFD)患者的临床转归。

方法

回顾性分析2021年7月至2022年10月在浙江大学医学院附属第一医院接受allo-HSCT患者

移植后早期(100 d内)出现以下情况之一: ①经验性抗细菌治疗72 h及以上持续发热

且血培养阴性患者; ②既往抗感染有效后再次出现不明原因高热; ③下呼吸道症状合并肺部CT病灶

经验性抗感染治疗无效。送检移植后外周血或支气管镜肺泡灌洗液行mNGS检测

并分析患者的总体生存率(overall survival

OS)和非复发死亡率(non-relapse mortality

NRM)。

结果

纳入60例患者

送检外周血标本47例

肺泡灌洗液标本13例。mNGS检测病原学阴性组19例

非真菌阳性组30例

真菌阳性组11例; 真菌阳性组中曲霉菌3例、毛霉菌5例、热带念珠菌2例、阿萨丝孢酵母菌1例。11例真菌阳性患者经调整抗真菌治疗8例获完全缓解。60例患者1年OS和1年NRM分别为70.0%(95%

: 64.1%~75.9%)和20.0%(95%

: 11.9%~32.5%)。真菌阳性组1年OS为54.5%(95%

: 49.5%~69.5%)

1年NRM为36.4%(95%

: 15.5%~70.3%); 阴性组、真菌阳性组和非真菌阳性组1年OS (

=0.487)和1年NRM (

=0.358)差异无统计学意义。真菌阳性组与非真菌阳性组OS (

=0.238)和NRM (

=0.154)上的差异亦无统计学意义。

结论

mNGS可快速诊断allo-HSCT后早期IFD

有利于及时有效治疗

改善患者的预后。

Abstract

Objective

To analyze the clinical outcomes of early invasive fungal disease (IFD) in patients after allogenetic hematopoietic stem cell transplantation (allo-HCST) with metagenomic next-generation sequencing (mNGS).

Methods

A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation: ① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer; ② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past; ③ Symptoms in lower respiratory tract associated with lung lesions on CT scan

and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS

and overall survival (OS) and non-relapse mortality (NRM) were analyzed.

Results

There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases

mNGS found that 19 cases were negative to pathogens

30 cases were non-fungal positive

and 11 case were fungal positive

including 3 cases of aspergillus

5 cases of mucor

2 cases of

Candida tropicalis

and 1 case of

Trichosporon asahii

.Of the 11 patients with fungal positive

8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0%(95%

: 64.1%~75.9%) and 20.0%(95%

: 11.9%~32.5%)

respectively

while those of the fungal infection patients were 54.5%(95%

: 49.5%~69.5%) and 36.4%(95%

: 15.5%~70.3%)

respectively.No significant differences were seen in 1-year O

S (

=0.487) and 1-year NRM (

=0.358) among the negative

fungal infection and non-fungal infection patients

neither OS (

=0.238) and NRM (

=0.154) between the fungal infection and the non-fungal infection patients.

Conclusion

mNGS can rapidly diagnose the early IFD after allo-HSCT

which is helpful for timely and effective treatment and improves the prognosis of patients.

关键词

Keywords

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