Risk factors for early death in children with haemophagocytic lymphohistiocytosis

Abstract

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. 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. 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 × 10(6) /L; aHR 5.1; 1.4-18.5, p = 0.012) at diagnosis, and thrombocytopenia (<40 × 10(9) /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. There seem to be easily available clinical predictors of early mortality in HLH patients, which may help guide treatment decisions.