Prognostic factors of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children: report of the Japan Histiocytosis Study Group

Pediatr Blood Cancer. 2014 Jul;61(7):1257-62. doi: 10.1002/pbc.24980. Epub 2014 Feb 17.

Abstract

Background: Despite several advances in the treatment of Epstein-Barr virus (EBV) in recent years, patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) do not always show satisfactory outcomes. We here conducted a nationwide survey in Japan to identify prognostic factors of EBV-HLH in children with this disease in an effort to improve the management and the outcomes of these patients.

Procedure: Between January 2003 and June 2008, we enrolled 98 children younger than 18 years of age who were diagnosed with EBV-HLH. We then studied the clinical characteristics and laboratory findings at the time of diagnosis with the aim to identify prognostic factors for EBV-HLH.

Results: The mean age of onset of EBV-HLH was 3.9 ± 2.8 years. Most of our patients presented with fever, hepatosplenomegaly, lymphadenopathy, and hemophagocytosis of bone marrow. Sixty-two percent of patients showed T cell clonality, and 97% had EBV infection in either T or natural killer cells. Most patients (60%) were treated with a multi-agent chemotherapeutic regimen, including corticosteroid, etoposide, and cyclosporine. After initial treatment, 90.3% of patients were in remission, and 7 patients (8.2%) experienced recurrence of EBV infection. Among several prognostic factors, patients with both hyperbilirubinemia (>1.8 mg/dl) and hyperferritinemia (>20,300 ng/ml) at the time of diagnosis had significantly poorer outcomes than those with low serum bilirubin and ferritin levels.

Conclusions: These findings suggest that the therapeutic strategy for children with EBV-HLH could be tailored according to the laboratory findings at diagnosis.

Keywords: Epstein-Barr virus; Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis; hyperbilirubinemia; hyperferritinemia.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Age of Onset
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Asian People
  • Bilirubin / blood
  • Child
  • Child, Preschool
  • Cyclosporine / administration & dosage
  • Data Collection*
  • Disease-Free Survival
  • Epstein-Barr Virus Infections* / blood
  • Epstein-Barr Virus Infections* / diagnosis
  • Epstein-Barr Virus Infections* / drug therapy
  • Epstein-Barr Virus Infections* / mortality
  • Etoposide / administration & dosage
  • Herpesvirus 4, Human*
  • Humans
  • Hyperbilirubinemia / blood
  • Hyperbilirubinemia / diagnosis
  • Hyperbilirubinemia / drug therapy
  • Hyperbilirubinemia / mortality
  • Immunosuppressive Agents / administration & dosage
  • Infant
  • Japan / epidemiology
  • Lymphohistiocytosis, Hemophagocytic* / blood
  • Lymphohistiocytosis, Hemophagocytic* / diagnosis
  • Lymphohistiocytosis, Hemophagocytic* / drug therapy
  • Lymphohistiocytosis, Hemophagocytic* / mortality
  • Remission Induction
  • Retrospective Studies
  • Survival Rate

Substances

  • Adrenal Cortex Hormones
  • Antineoplastic Agents, Phytogenic
  • Immunosuppressive Agents
  • Etoposide
  • Cyclosporine
  • Bilirubin