Diagnostic value of plasma microbial cell-free DNA sequencing in hematopoietic stem cell transplant recipients: A systematic review and meta-analysis

Hematopoietic stem cell transplant (HSCT) recipients are at increased risk for a wide spectrum of infections, including opportunistic infections with atypical presentations. Diagnosis can be challenging and often requires extensive testing and invasive procedures. Sequencing of plasma microbial cell-free DNA (mcfDNA) allows non-invasive untargeted detections of human pathogens, making this modality appealing for this patient population. The purpose of this study was to perform a meta-analysis to evaluate the diagnostic value of sequencing of plasma mcfDNA for infections in HSCT recipients. We searched for relevant articles in BASE, PubMed, and ClinicalTrials.gov from January 1996 to November 2022. Studies were eligible for inclusion if they assessed the diagnostic performance of sequencing of plasma mcfDNA and included HSCT recipients with sufficient data to assign plasma mcfDNA test results as true positive, true negative, false positive, or false negative, which were used to calculate diagnostic test accuracy. A total of 6 studies and 69 patients were included. All included studies were published in 2019 or later and were conducted in the United States. Three studies were exclusively pediatric, two exclusively adult, and one a mixture of both adult and pediatric patients. The pooled sensitivity was 0.90 (95% CI 0.71-0.97) and the pooled specificity was 0.75 (0.49-0.90). The high pooled diagnostic odds ratio suggests that sequencing of plasma mcfDNA may have a unique diagnostic role in HSCT recipients. Its high sensitivity and capability to detect a broad array of pathogens makes it a promising adjunct to traditional diagnostic testing.