Background: Immunocompromised children with malignancies or after hematopoietic cell transplantation (HCT) often deteriorate before conventional cultures identify a pathogen. Next-generation sequencing (NGS) promises faster, broader detection, yet its clinical impact in pediatric oncology remains unclear. This review aimed to assess the diagnostic performance and clinical utility of NGS in this population. Methods: We searched PubMed, Embase, and Scopus from January 2010 to April 2025 for studies evaluating NGS (metagenomic, targeted, or whole-genome sequencing) in pediatric oncology or HCT patients meeting predefined eligibility criteria. Duplicate screening, data extraction, and Joanna Briggs Institute risk-of-bias appraisal were performed. Heterogeneity precluded formal meta-analysis; findings were synthesized using narrative synthesis complemented by limited quantitative analyses. The protocol was not registered. Results: Twenty-four studies (≥2700 children; 2019–2025) met inclusion criteria. Metagenomic NGS (mNGS) was the most common approach, applied to blood/plasma (46%), bronchoalveolar fluid (BALF) (21%), and other fluids. In culture-negative sepsis or persistent febrile neutropenia, mNGS detected pathogens in 69–86% of episodes versus 18–56% for culture/polymerase chain reaction (PCR). Described in limited studies, early (<48 h) testing shortened fever by ~1.5 days and cut antimicrobial costs by 25–30%. Across studies, treatment was escalated, de-escalated, or discontinued in a median of 63% of mNGS-positive cases. Whole-genome sequencing (WGS) identified 18 silent transmission clusters and resolved a multidrug-resistant Acinetobacter baumannii outbreak within hours. Conclusions: NGS benefits pediatric hemato-oncology by accelerating pathogen-directed therapy, supporting antimicrobial stewardship, and enhancing outbreak surveillance. Despite cost and standardization barriers, evidence supports its use in selected high-risk patients.
Jabłońska et al. (2025) studied this question.