Tuberculosis After Allogeneic Hematopoietic Cell Transplant: A 15-Year Case Series Highlighting Diagnostic Challenges

Tuberculosis (TB) is an uncommon but potentially fatal complication after allogeneic hematopoietic cell transplant (HCT). Diagnosis is often delayed due to nonspecific clinical presentations, limited sensitivity of screening tests for latent TB infection, and slow turnaround of conventional TB diagnostic methods. The study aim is to describe the clinical and diagnostic characteristics of allogeneic HCT recipients with TB in the era of molecular and sequence based diagnostic methods. We conducted a retrospective review of microbiologically confirmed TB cases among HCT recipients at a tertiary cancer center from 2010 to 2025. We detail clinical, demographic, and diagnostic characteristics including metagenomic next-generation sequencing (mNGS) testing of bronchoalveolar lavage (BAL) and blood (Eurofins Viracor, Lenexa, KS) for 2 individuals. Ten patients were diagnosed with active TB at a median of 122 days post-HCT (range: 36 to 2557). The median age was 53 yr, and 6 were male. Except for 1 patient, all patients were foreign-born. Pre-HCT TB screening was performed in 7 patients; however, only 3 had positive (tuberculin skin test, n = 1; interferon-gamma release assay [IGRA], n = 2), and 1 had indeterminate IGRA results. All patients had abnormal CT chest findings compatible with latent TB. Nine of 10 patients presented with either fever or cough, while 1 patient was asymptomatic with incidental radiographic abnormalities. TB was diagnosed by Mycobacterium tuberculosis (MTB) complex PCR in 8 cases, 4 patients had disseminated TB, and 3 died. mNGS results were available in 2 patients. In both cases MTB was detected in BAL, and in 1, MTB was detected in the blood. Among 9 patients with available susceptibility testing data, moxifloxacin resistance was identified in 1 case. In our cohort, post-HCT TB occurred mainly in foreign-born patients. Infection was diagnosed early after transplant and was frequently disseminated, with high mortality. These results underscore the limitations of current screening methods, and the diagnostic challenges of post-HCT TB.