Metagenomics Next-Generation Sequencing for Identifying Pathogens in Central Nervous System Complications after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract:

Objective: Central nervous system (CNS) infections are severe neurological complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical usefulness of metagenomic next-generation sequencing (mNGS) remains underdiscussion in diagnosis of CNS infections after allo-HSCT. We conducted a prospective study to compare mNGS and conventional testing in investigating the pathogens of CNS infections in allo-HSCT recipients.

Methods: Patients with CNS manifestations accompanying with viruses associated diseases or viremia and patients with unexplainable CNS manifestations were enrolled in this study. Pathogens detected by mNGS only were further confirmed by validated testing.

Results: Of 53 patients enrolled in this study, 36 episodes of CNS infections were diagnosed in 35 patients including 35 clinical and microbiologic confirmed infections and 1 clinical confirmed infection.Among these 36 episodes, mNGS identified 5 that were not identified by conventional testing and 4 of the 5 obtained a clinical effect with adjusting treatments. Among the remaining 31 infections, metagenomic NGS made concurrent diagnoses with conventional testing in 30 and 1 diagnosed without etiological evidence both by conventinal testing and mNGS. Viruses were the most common pathogens with EBV(12/34) was the most frequent, followed by HHV-6(9/34), HSV-1(4/34), CMV(3/34), adenovirus(3/34), VZV(2/34), HHV-7(1/34). The 2-year cumulative incidence of overall CNS infections and CNS viral infections post-transplantation were 7.4±0.01% and 6.2%±0.01%, respectively.