Metagenomic Next-Generation Sequencing for Pathogens in Bronchoalveolar Lavage Fluid Improve the Survival of Patients with Pulmonary Complications after Allogeneic Hematopoietic Stem Cell Transplantation

Background：The incidence and mortality of pulmonary complications after allogeneic Hematopoietic stem cell transplantation (allo-HSCT) are high. In clinical practice, diagnosis of post-allogeneic HSCT pulmonary complications is usually challenging, which may lead to antibiotic abuse and the high mortality. Unbiased metagenomic next generation sequencing (mNGS) has been used for infection diagnosis. In this study, we aimed to explore the real-world clinical application value of mNGS for pulmonary complications diagnosis after allo-HSCT.Method: From August 2019 to June 2021, We retrospectively investigated the results of mNGS in bronchoalveolar lavage fluid (BALF) and conventional tests from 134 hospitalized cases after allo-HSCT with suspected pulmonary complication and compared the diagnostic performance of pathogens. The effect of clinical management of overall survival were also assessed.Results: Total 134 cases of 101 patients with pulmonary complications were enrolled into the study. More pathogens were identified by mNGS compared by conventional tests (226 vs 120). Among the positive pathogens by mNGS (n= 266), there were 87(87/266,32.71%)strains of bacteria, 33(33/266,12.41%) stains of fungi and 146(146/266,54.89%) strains of viruses. Compared to conventional tests, mNGS had a higher diagnostic sensitivity (80.99% vs 59.50%, P<0.001) and no significant differences were found in specificity (61.54% vs 92.31%, P=0.125). Furthermore, the sensitivity can be elevated with the combination of two tests. The sensitivity of mNGS outperformed in virus (93.94% vs 69.70%, P=0.021), while it was opposite in fungi (36% vs 80%, P=0.013). For bacteria, there were no significant difference in the diagnostic sensitivity (65.85% vs 52.44%, P=0.144). As for Pneumocysti jiroveci, both sensitivity (100%) and specificity (99.12%) of mNGS were very high. Among all 101 patients who were followed up for 6 months, there were 18 patients died, 11 of whom died due to pulmonary complications. In addition, The six-month overall survival(OS) of 88.89% in early group (received mNGS≤7days) was significantly higher than that of OS (65.52%)（HR=0.287, 95%CI：0.101-0.819，P=0.006）in late group(received mNGS＞7 days) and no-relapse mortality(NRM) of 9.72% in early group was significantly lower than that of NRM(27.59%)( HR=0.313, 95%CI：0.099-0.986，P=0.019) in late group.Conclusions: mNGS shows high sensitivity for pathogen identification, which is helpful for clinical management. At the same time, mNGS has the potential to detect potential pathogens in these immunosuppressed patients. Early mNGS can improve prognosis of patients with pulmonary complications after allo-HSCT. Thereby it could be a promising technology for clinical first-line diagnosis of patients with pulmonary complications after allo-HSCT.

No relevant conflicts of interest to declare.