Risk factors for early death in children with haemophagocytic lymphohistiocytosis

Acta Paediatr. 2012 Mar;101(3):313-8. doi: 10.1111/j.1651-2227.2011.02501.x. Epub 2011 Nov 17.

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 × 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.

Conclusion: There seem to be easily available clinical predictors of early mortality in HLH patients, which may help guide treatment decisions.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Inflammatory Agents / therapeutic use
  • Child
  • Cyclosporine / therapeutic use
  • Dexamethasone / therapeutic use
  • Drug Therapy, Combination
  • Etoposide / therapeutic use
  • Female
  • Ferritins / blood
  • Fever / etiology
  • Humans
  • Hyperbilirubinemia / etiology
  • Immunosuppressive Agents / therapeutic use
  • Leukocytosis / cerebrospinal fluid
  • Leukocytosis / etiology
  • Lymphohistiocytosis, Hemophagocytic / complications
  • Lymphohistiocytosis, Hemophagocytic / drug therapy
  • Lymphohistiocytosis, Hemophagocytic / metabolism
  • Lymphohistiocytosis, Hemophagocytic / mortality*
  • Male
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • Thrombocytopenia / etiology

Substances

  • Anti-Inflammatory Agents
  • Immunosuppressive Agents
  • Etoposide
  • Dexamethasone
  • Cyclosporine
  • Ferritins