Risk factors for early death in children with haemophagocytic lymphohistiocytosis
- 24 October 2011
- journal article
- research article
- Published by Wiley in Acta Paediatrica
- Vol. 101 (3), 313-318
- https://doi.org/10.1111/j.1651-2227.2011.02501.x
Abstract
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 (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.Keywords
This publication has 26 references indexed in Scilit:
- Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocolBlood, 2011
- Rate of decline of ferritin in patients with hemophagocytic lymphohistiocytosis as a prognostic variable for mortalityPediatric Blood & Cancer, 2010
- Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cellsJCI Insight, 2009
- Familial Hemophagocytic Lymphohistiocytosis Type 5 (FHL-5) Is Caused by Mutations in Munc18-2 and Impaired Binding to Syntaxin 11American Journal of Human Genetics, 2009
- Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosisBritish Journal of Haematology, 2007
- Defective cytotoxic lymphocyte degranulation in syntaxin-11–deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patientsBlood, 2007
- Familial and acquired hemophagocytic lymphohistiocytosisEuropean Journal of Pediatrics, 2006
- Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type IIBlood, 2006
- Munc13-4 Is Essential for Cytolytic Granules Fusion and Is Mutated in a Form of Familial Hemophagocytic Lymphohistiocytosis (FHL3)Cell, 2003
- Hemophagocytic lymphohistiocytosis in infancy and childhoodThe Journal of Pediatrics, 1997