Risk factors for early death in children with haemophagocytic lymphohistiocytosis

Aim: Haemophagocytic lymphohistiocytosis (HLH) is a life‐threatening disturbance of immunoregulation. HLH comprises primary and acquired forms with different disease severity. A large proportion of deaths occur early into treatment. We investigated association with early death for laboratory and clinical parameters before the start of and 2 weeks into therapy. Methods: A total of 232 children from Scandinavia, Germany or Italy, fulfilling diagnostic criteria and/or with familial disease and/or HLH‐causing mutations, receiving HLH treatment 1994–2008 were included. The relation between clinical findings and early pre‐transplant death was examined using the Cox proportional hazards model, with a 4‐month right‐truncation of the outcome. Patients were censored at last follow‐up or transplant. Statistically significant predictors were adjusted for sex, age and each other. Results: The following features were significantly associated with adverse outcome: hyperbilirubinaemia (>50 μmol/L; adjusted hazard ratio (aHR) 3.2; 95% confidence interval 1.3–8.1, p = 0.011), hyperferritinaemia (>2000 μg/L; aHR 3.2; 1.2–8.6, p = 0.019), cerebrospinal fluid pleocytosis (>100 × 10⁶/L; aHR 5.1; 1.4–18.5, p = 0.012) at diagnosis, and thrombocytopenia (<40 × 10⁹/L; aHR 3.4; 1.1–10.7, p = 0.033), and hyperferritinaemia (>2000 μg/L; aHR 10.6; 1.2–96.4, p = 0.037) 2 weeks into therapy. Non‐improvement of fever, anaemia and/or thrombocytopenia also had adverse impact. Conclusion: There seem to be easily available clinical predictors of early mortality in HLH patients, which may help guide treatment decisions.