Metagenomic Next-Generation Sequencing for Pathogens in Bronchoalveolar Lavage Fluid Improves the Survival of Patients with Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation

Zaihong Shen; Ying Wang; Aihua Bao; Jun Yang; Xi Sun; Yu Cai; Liping Wan; Chongmei Huang; Xiaowei Xu; Jiahua Niu; Xinxin Xia; Chang Shen; Yu Wei; Huiying Qiu; Kun Zhou; Min Zhang; Yin Tong; Xianmin Song

doi:10.1007/s40121-023-00850-w

Metagenomic Next-Generation Sequencing for Pathogens in Bronchoalveolar Lavage Fluid Improves the Survival of Patients with Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation

Infect Dis Ther. 2023 Aug;12(8):2103-2115. doi: 10.1007/s40121-023-00850-w. Epub 2023 Aug 4.

Authors

Zaihong Shen^#^{1

2}, Ying Wang^#¹, Aihua Bao^#³, Jun Yang¹, Xi Sun¹, Yu Cai¹, Liping Wan¹, Chongmei Huang¹, Xiaowei Xu¹, Jiahua Niu¹, Xinxin Xia¹, Chang Shen¹, Yu Wei¹, Huiying Qiu¹, Kun Zhou¹, Min Zhang^#³, Yin Tong^#¹, Xianmin Song^#⁴

Affiliations

¹ Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
² Department of Hematology, Taizhou First People's Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou City, 318020, Zhejiang Province, China.
³ Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
⁴ Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. shongxm@sjtu.edu.cn.

^# Contributed equally.

Abstract

Introduction: Unbiased metagenomic next-generation sequencing (mNGS) has been used for infection diagnosis. In this study, we explored the clinical diagnosis value of mNGS for pulmonary complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: From August 2019 to June 2021, a prospective study was performed to comparatively analyze the pathogenic results of mNGS and conventional tests for bronchoalveolar lavage fluid (BALF) from 134 cases involving 101 patients with pulmonary complications after allo-HSCT.

Results: More pathogens were identified by mNGS than with conventional tests (226 vs 120). For bacteria, the diagnostic sensitivity (P = 0.144) and specificity (P = 0.687) were similar between the two methods. For fungus except Pneumocystis jirovecii (PJ), conventional tests had a significantly higher sensitivity (P = 0.013) with a similarly high specificity (P = 0.109). The sensitivities for bacteria and fungi could be increased with the combination of the two methods. As for PJ, both the sensitivity (100%) and specificity (99.12%) of mNGS were very high. For viruses, the sensitivity of mNGS was significantly higher (P = 0.021) and the negative predictive value (NPV) was 95.74% (84.27-99.26%). Pulmonary infection complications accounted for 90.30% and bacterium was the most common pathogen whether in single infection (63.43%) or mixed infection (81.08%). The 6-month overall survival (OS) of 88.89% in the early group (mNGS ≤ 7 days) was significantly higher than that of 65.52% (HR 0.287, 95% CI 0.101-0.819, P = 0.006) in the late group (mNGS > 7 days).

Conclusions: mNGS for BALF could facilitate accurate and fast diagnosis for pulmonary complications. Early mNGS could improve the prognosis of patients with pulmonary complications after allo-HSCT.

Trial registration: ClinicalTrials.gov identifier, NCT04051372.

Keywords: Allogeneic hematopoietic stem cell transplantation; Bronchoalveolar lavage fluid; Metagenomic next-generation sequencing (mNGS); Pulmonary complication.

Associated data

ClinicalTrials.gov/NCT04051372

Abstract

Associated data

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