Tuberculosis poses a rare but life-threatening complication for patients undergoing hematopoietic stem cell transplantation. In a case series spanning January 2020 to January 2024, we evaluated the application of metagenomic Next-Generation Sequencing in the early diagnosis of tuberculosis in patients following allogeneic hematopoietic stem cell transplantation. We identified 9 cases of post-transplant tuberculosis, predominantly pulmonary, with 1 case of disseminated disease. In early fluid samples from patients with post-transplant active tuberculosis, metagenomic next-generation sequencing detected Mycobacterium tuberculosis complex earlier than conventional tests, enabling rapid diagnosis. In this study, metagenomic next-generation sequencing showed a sensitivity of 66.6% and specificity of 100%, higher than TB-DNA and Xpert (55.6%). Concurrently, among mNGS-positive samples, 4 (44.4%) were from peripheral blood and 3 (33.3%) from bronchoalveolar lavage fluid. The combination of metagenomic Next-Generation sequencing and Xpert may enhance the capacity for detecting Mycobacterium tuberculosis complex in extrapulmonary specimens from post-transplant patients. The time from symptom onset to Next-Generation Sequencing positivity was 2 to 76 days, and from transplantation to TB diagnosis was 30 to 485 days. Despite some fatalities, the majority of patients completed extended anti-tuberculosis treatment and are under regular follow-up, highlighting the value of Next-Generation Sequencing in diagnosing tuberculosis in this high-risk population.
