title: Prognostic factors of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children: report of the Japan Histiocytosis Study Group.
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.
  
  
  METHODS
  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.
authors.affiliation: Tsuchiya Children's Hospital, Kuki, Saitama, Japan; HLH/LCH Committees in the Japanese Society of Pediatric Hematology, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kogawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Asano
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakiguchi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Megumi
authors.initials: M
authors.lastname: Oda
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D017668:Age of Onset; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D044466:Asian People; D001663:Bilirubin / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage; D003625:Data Collection; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D005047:Etoposide / Q000008:administration & dosage; D004854:Herpesvirus 4, Human; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007223:Infant; D007564:Japan / Q000453:epidemiology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000305:Adrenal Cortex Hormones; D000972:Antineoplastic Agents, Phytogenic; D007166:Immunosuppressive Agents; D005047:Etoposide; D016572:Cyclosporine; D001663:Bilirubin
keywords: Epstein-Barr virus; Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis; hyperbilirubinemia; hyperferritinemia