E004 Infection risk in adults with haemophagocytic lymphohistiocytosis (HLH): experience from a specialist centre

Abstract Background/Aims Secondary haemophagocytic lymphohistiocytosis (sHLH) is a rare and severe hyperinflammatory condition with high morbidity and mortality, caused by an abnormal immune response to various triggers, requiring multispecialty management across rheumatology, haematology and infectious diseases. Infections are an established trigger for sHLH and infection can also arise as a complication during the disease course; however, there are sparse published data in relation to the latter. Increasing recognition of infection-related morbidity at a specialist tertiary hospital prompted the development of a HLH antimicrobial prophylaxis guideline (available online). Here, we describe infective complications in adults with sHLH. Methods A retrospective single-centre cohort study was conducted at University College London Hospital (UCLH) in two phases. Adults (≥ 18 years) with confirmed sHLH (HScore 169 or multidisciplinary team diagnosis) admitted between April 2019 and April 2021 were included in phase A (pre-guideline), and following implementation of HLH antimicrobial prophylaxis guidelines in October 2021, equivalent data were collected in phase B between January 2022 and January 2024. Demographics, triggers, immunosuppression, antimicrobial prophylaxis, infective complications, intensive care admission and hospital mortality were extracted from clinical records. Fisher’s exact test and Mann-Whitney tests were applied to categorical and continuous comparisons, respectively. Results 98 adults were included in the analysis, with 40 in phase A (pre-guideline) and 58 in phase B (post-guideline). Median age was similar across both cohorts (37 - 43 years) and corticosteroids and anakinra were widely used. Antimicrobial prophylaxis use increased markedly post-guideline, from patients receiving antivirals (52.5%), antifungals (37.5%) or specifically anti-Pneumocystis jirovecci (PCP) prophylaxis (42.5%) in phase A, to over 85% in all categories in phase B. 60% (24/40) in phase A and 62.1% (36/58) of patients in phase B developed at least one infection during admission, with some patients developing multiple infections. Bacterial infections were most frequent in both cohorts (50%), followed by fungal and viral infections. Mortality amongst those with fungal disease was lower in phase B (63.4% phase B vs 88.9% phase A), and there were no HSV infections after guideline introduction. Mortality remained high overall (30%) and in both phases, patients without infective complications were more likely to survive. This was statistically significant for phase A (OR = 5.92, 95% CI 1.10 - 31.95, Fisher’s exact p-value 0.04) but not for phase B (OR = 2.43, 95% CI 0.73-8.04, Fisher’s exact p-value 0.17). Conclusion Infective complications occur in most adults with sHLH and are associated with poorer survival. Fungal infections carry the greatest mortality risk, highlighting a high-need subgroup. Introduction of a formalised antimicrobial prophylaxis guideline was associated with fewer deaths among those with fungal disease, despite more intensive immunosuppression regimens. These findings underscore the importance of proactive infection prevention and support further optimisation of antimicrobial prophylaxis strategies. Disclosure P. Saha: None. N. McCann: None. M. Chowdhury: None. A.M. Holloway: Grants/research support; A.H. was supported by UCLH Charity Grant 2024 (7253). D. Shah: None. N. Sah: None. N. Kvam: None. A. Jones: None. M. Brown: None. J. Manson: None.