Reactivation of multi-drug resistant tuberculosis following allogeneic stem cell transplantation in a UK centre

Background: Current data indicate a rising incidence of tuberculosis in the UK, affecting both UK-born and non-UK-born individuals. Although infrequent, reactivation of TB post-stem cell transplantation can be devastating. Due to limitations and paucity of available data, there is currently no evidence-based strategy for screening and prophylaxis as part of transplant work-up. 

Case Report: A 44-year old female of Filipino origin underwent chemotherapy treatment of an intermediate risk acute myeloid leukaemia (AML) in a UK centre. She was treated multiply for persistent fevers associated with new inflammatory changes in the right upper lung, although chest radiograph at diagnosis was normal. The patient was not screened for latent tuberculosis on entry to the UK, falling outside current age criteria for inclusion. Extensive investigation for tuberculosis was undertaken, with collaboration between haematology and infection teams, yielding negative results. The patient was therefore empirically treated for invasive fungal infection. In first complete remission, an allogenic stem cell transplant was performed. Throughout, the patient experienced unremitting high-grade fevers, treated with both antifungal and antibacterial agents. Computerised tomography showed a peri-hilar mass, with mediastinal and hilar lymphadenopathy. A spontaneous sputum sample later became smear positive for alcohol acid fast bacilli, confirmed with bronchoalveolar lavage the same week. Whole genome sequencing identified multi-drug resistance. A slow but steady clinical improvement was seen with anti-tuberculous treatment, with no evidence of AML recurrence to date. 

Conclusion: A multi-disciplinary team approach resulted in a favourable outcome, highlighting the value of an integrated approach to diagnosis and management of reactivation. Going forward, further research is crucial to forming evidence-based guidelines for latent tuberculosis screening and prophylaxis in stem cell transplant. Co-development of research with experts in higher burden settings, and a collaborative approach to guideline development, are essential to addressing the potential impact of changing epidemiology on clinical practice.