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

## TL;DR

This study shows that metagenomic sequencing can detect oropharyngeal colonization in stem cell transplant patients more effectively than traditional methods, and that certain bacterial colonizations predict worse transplant outcomes.

## Contribution

The study demonstrates the clinical value of metagenomic next-generation sequencing in predicting transplant prognosis through oropharyngeal colonization screening.

## Key findings

- mNGS detected a 49.2% oropharyngeal colonization rate compared to 15.6% with traditional culture methods.
- Oropharyngeal Enterobacteriaceae colonization was linked to higher infection and mortality risks after transplantation.
- CRE colonization was associated with delayed engraftment and significantly worse survival outcomes.

## 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.

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.

This study is registered as a single-center clinical trial (Registration No. ChiCTR2300069450).