PF319 A DUAL CENTRE EXPERIENCE OF HAEMOPHAGOCYTOSIS REVEALS ULTRA-HIGH FERRITIN (&gt;50,000 NG/ML) AND NEUTROPENIA AS PREDICTORS OF MORTALITY
Authors: C. Hockings, J.-S. Shin, F.-E. Sin, J. Manson, C. McNamara
Journal: HemaSphere (2019)

Background: Haemophagocytic lymphohistiocytosis (HLH) is a poorly understood entity, characterised by a diffuse array of underlying precipitants and frequent delayed diagnosis despite scoring systems. Patients may be assessed for possible HLH by various specialties including infectious diseases, haematology and rheumatology who have different approaches and familiarity with available treatments and diagnostic tools. Aims: To identify factors in HLH presentation and care correlating to outcomes. Methods: Patients of interest were identified by key phrases “histiocytosis”, “HLH” or “haemophagocytosis” on SIHMDS reports or by diagnostic coding for HLH from 2014–2018. Clinical data was collected from electronic case notes on patients in whom a diagnosis of HLH had been made. Results: Only 29 of 81 bone marrow aspirates reported as having haemophagocytosis had a subsequent HLH diagnosis (PPV 36%). Conversely 5 of 34 patients in whom the diagnosis was made had no evidence of histiocytosis on BM sampling (sensitivity 85%). Clinical data was available on 27 patients diagnosed with HLH. 10 patients had an underlying diagnosis of lymphoma with other precipitants including malignancies and infection. Outcomes were poor with 48% survival at 100 days post presentation. All patients had serum ferritin >500ng/ml on presentation. Peak ferritins of >50,000ng/ml were seen in 9 patients (33%), >10,000ng/ml in 22 (81%). Hyperferritinaemia correlated with mortality: 39% where peak ferritin <50,000ng/ml, 78% if >50,000ng/ml. Cytopenias were defined as Hb<90 g/dl, Neutrophils <1 x 109 or platelets <100 x 109. All patients with monocytopenia survived (n = 4). 10 of 12 patients with trilineage cytopenia died (83%) compared to 4 of 15 patients with 2 or fewer cytopenias (27%). NK cell activity and soluble CD25 quantification were not available on any patients. HLH-2004 scores ranged from 3–6; mean 4.64. Internal referrals had no difference in survival to those transferred from other centres (46 vs 50% respectively) but showed a higher mean HLH-2004 score (4.9 vs 3.8). The most common treatment given was steroids (n = 27, 63%). Only 4 patients (15%) received Anakinra, all having received at least one line of prior therapy. Other treatments were from the HLH-2004 protocol: Etoposide n = 11, 41%; Ciclosporin n = 9, 33%. 4 patients died before any treatment was given. Summary/Conclusion: Haemophagocytosis on bone marrow had a very poor positive predictive value. Sensitivity was also not significantly superior to serum ferritin >10,000 (85 vs 81%). Ferritin was also shown to have a value in outcome prediction as well as diagnosis. Neutropenia was always seen in association with trilineage cytopenias and was predictive of poor outcomes (83 vs 27% mortality). Diagnoses of HLH are being made clinically at scores of <5 (HLH-2004 threshold) due to the lack of availability of tests such as soluble CD25. Although patients not immediately centrally referred had equivalent outcomes this is likely biased by fitness for transfer, and difference in HLH-2004 criteria in these patients. It appears patients are being referred on for diagnostic uncertainty rather than to improve outcomes by centralisation of care and greater availability of targeted therapy and clinical expertise. We are currently collaborating as part of HASC (HLH across speciality collaboration), a national group working to improve knowledge of HLH amongst the general medical population. By encouraging earlier diagnosis and centralised referral we hope to improve outcomes and further establish the role of Anakinra in treating these patients.