Clinical value of metagenomic next-generation sequencing in screening oropharyngeal colonization in patients undergoing allogeneic hematopoietic stem cell transplantation: a prospective observational study

宏基因组二代测序在接受异基因造血干细胞移植患者口咽部定植筛查中的临床价值:一项前瞻性观察研究

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Abstract

Screening for colonization is an essential procedure in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although metagenomic next-generation sequencing (mNGS) has played an important role in the diagnosis of complex and challenging infections, its effectiveness in screening oropharyngeal colonization is not yet fully assessed. We performed a prospective analysis (ChiCTR2300069450) involving 128 allo-HSCT patients between June 2022 and June 2023. Before the conditioning regimen, all patients underwent oropharyngeal and anal swab tests to detect colonizing pathogens. In addition to culture-based methods, we also analyzed oropharyngeal swab samples using mNGS. Among the allo-HSCT patients, the overall colonization rate from cultures was 15.6%, while mNGS identified an oropharyngeal colonization rate of 49.2%. Patients with oropharyngeal Enterobacteriaceae colonization had a higher incidence of post-transplant bloodstream infection (BSI) (39.1% vs 19.0%, P = 0.034) and thrombotic microangiopathy (17.4% vs 8.5%, P = 0.04). Multivariate analysis confirmed oropharyngeal Enterobacteriaceae colonization as an independent risk factor for non-relapse mortality (NRM), overall survival (OS), and progression-free survival (PFS) (P = 0.024, 0.030, and 0.021, respectively). The individuals with carbapenem-resistant Enterobacteriaceae (CRE) colonization experienced delayed platelet engraftment (P = 0.018). Moreover, they had significantly worse OS (P = 0.002), higher NRM (P = 0.00015), and poorer PFS (P = 0.00095). Screening for oropharyngeal colonization using mNGS provides critical clinical value in predicting transplant prognosis. Clinicians should closely monitor patients with oropharyngeal Enterobacteriaceae or CRE colonization. IMPORTANCE: Screening for colonization is essential for predicting infection risk in allo-HSCT patients. Traditional microbiological testing methods, however, are time-consuming and have low sensitivity. In this paper, we examine the impact of oropharyngeal colonization on outcomes following allo-HSCT while also evaluating the utility of mNGS for detecting colonization. Our investigation reveals that screening for oropharyngeal colonization using mNGS provides critical clinical value in predicting transplant outcomes and prognosis. Additionally, not all colonization has clinical relevance, but oropharyngeal Enterobacteriaceae colonization has negative impacts on transplant prognosis. Colonization by CRE had particularly severe consequences, which warrants serious attention. CLINICAL TRIALS: This study is registered as a single-center clinical trial (Registration No. ChiCTR2300069450).

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