Targeted next-generation sequencing has comparable clinical value to metagenomic NGS for pulmonary infections in hematological malignancy patients: a real-world propensity score-matched study

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is widely recognized in immunocompromised populations due to its unbiased ability to identify pathogens, while targeted next-generation sequencing (tNGS) combines PCR amplification with high-throughput sequencing technology, with advantages of lower costs and shorter turnaround times. However, it remains unclear whether tNGS can be applied in the same way as mNGS for immunodeficient patients with hematologic malignances (HM). METHODS: This retrospective study analyzed clinical data from 245 HM patients suspected of pneumonia between April 2019 and April 2024. Bronchoalveolar lavage fluid (BALF) samples were tested using either tNGS or mNGS. Propensity score matching (PSM) (1:1) balanced the groups. RESULTS: tNGS and mNGS showed comparable sensitivity, specificity, and accuracy for pathogen detection (97.3% vs 94.2%, 26.3% vs 26.1%, 82.6% vs 77.2%; all P > 0.05), with similar accuracy across immunodeficiency states (severe immunodeficiency: 80.0% vs 81.8%; non-severe immunodeficiency: 64.7% vs 86.7%; both P > 0.05). For non-severe pneumonia, tNGS was comparable to mNGS (accuracy: 77.9% vs 86.3%, P > 0.05), but mNGS was significantly superior in severe cases (accuracy: 50.0% vs 100.0%, P = 0.002). Both groups improved rate of correct antibiotic use (tNGS: 50.9% to 84.3%; mNGS: 57.1% to 77.8%, P < 0.01) and reduced overuse rates (tNGS: 25.9% to 2.8%; mNGS: 4.8% to 25.4%; P < 0.01), with no difference in chemotherapy intervals (37.5 ± 22.9 days vs 41.0 ± 38.4 days; P = 0.89). CONCLUSION: In HM patients suspected of pulmonary infection, BALF-tNGS showed comparable diagnostic efficacy as BALF-mNGS, with similar clinical value across varying immunodeficiency states. tNGS is a viable alternative for non-severe pneumonia, while mNGS is superior in severe cases. Collectively, the findings of this study highlight tNGS as an alternative diagnostic approach for HM patients.