E035 An evaluation of the causes and outcomes of haemophagocytic lymphohistiocytosis in Sheffield Teaching Hospitals: 2016 to 2021

Abstract

Abstract Background/Aims Haemophagocytic lymphiohistiocytosis (HLH) is a rare, underrecognised hyperinflammatory syndrome, characterised by immune dysregulation. Without treatment, the ensuing cytokine storm leads to high mortality. Secondary HLH (sHLH) is triggered by malignancy, infection, autoimmunity and medicines; treatment with immunosuppression is consensus- rather than evidence-based and extrapolated from primary HLH. Sheffield hosts a mature HLH multidisciplinary advisory group (MDAG). Here we evaluate the cause, treatment, requirement for critical care and mortality of people with HLH managed through the MDAG in a period including the coronavirus pandemic but prior to NHS England approval of anakinra (IL-1 antagonist) for HLH. Methods This retrospective evaluation (approved locally STH 10850) identified patients from MDAG records 1st October 2016 to 30th September 2021. Data from electronic/paper records was analysed using Microsoft Excel. Results HLH triggers were infection (viral 34%, bacterial 10%), haematological (35%), rheumatological (13%) and other (8%). Rheumatological causes were Still’s disease (n = 5); antiphospholipid syndrome (n = 2); JO1 dermatomyositis (n = 1); SLE (n = 1); and rheumatoid arthritis (n = 1). Other causes included unknown (n = 3); combined systemic JIA and sickle cell crisis (n = 1); medication (alemtuzumab) (n = 1); and primary HLH (n = 1). Overall mortality was 53% and highest in HLH with a haematological malignancy trigger (82%) Prior to the COVID19 pandemic (pre-March 2020), the commonest trigger of HLH was haematological malignancy (47%); after March 2020, the commonest trigger was infection (64%); COVID-19 explained 42% of cases. Mortality fell from 72% to 31%. Conclusion In this real-world series of people with HLH, mortality and critical care requirement was high. HLH triggers reflect published evidence as does poor prognosis in haematological malignancy-associated HLH. No-HLH associated with non-haematological malignancy was identified; we may need to improve MDAG reach into oncology. Seeming reduction in mortality following the COVID-19 pandemic may reflect increased recognition of COVID-19 induced hyperinflammation along with locally-agreed access to anakinra for COVID-19-induced HLH. The increase in infection related HLH cases since March 2020 is explained largely by COVID-19 cases. This has led to a relative reduction in cases related to haematological malignancy. HLH requires multidisciplinary management and better research to improve treatment. Disclosure B. Awdas: None. T. Nadin: None. R. Tattersall: None.