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

• Published in: Pediatric blood & cancer Vol. 61; no. 7; pp. 1257 - 1262
• Main Authors: Kogawa, Kazuhiro, Sato, Hiroki, Asano, Takeshi, Ohga, Shouichi, Kudo, Kazuko, Morimoto, Akira, Ohta, Shigeru, Wakiguchi, Hiroshi, Kanegane, Hirokazu, Oda, Megumi, Ishii, Eiichi
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2014; Wiley Subscription Services, Inc
• Subjects: Adrenal Cortex Hormones - administration & dosage; Age of Onset; Antineoplastic Agents, Phytogenic - administration & dosage; Asian Continental Ancestry Group; Bilirubin - blood; Child; Child, Preschool; Cyclosporine - administration & dosage; Data Collection; Disease-Free Survival; Epstein-Barr virus; Epstein-Barr Virus Infections - blood; Epstein-Barr Virus Infections - diagnosis; Epstein-Barr Virus Infections - drug therapy; Epstein-Barr Virus Infections - mortality; Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis; Etoposide - administration & dosage; Hematology; Herpesvirus 4, Human; Humans; hyperbilirubinemia; Hyperbilirubinemia - blood; Hyperbilirubinemia - diagnosis; Hyperbilirubinemia - drug therapy; Hyperbilirubinemia - mortality; hyperferritinemia; Immunosuppressive Agents - administration & dosage; Infant; Japan - epidemiology; Lymphohistiocytosis, Hemophagocytic - blood; Lymphohistiocytosis, Hemophagocytic - diagnosis; Lymphohistiocytosis, Hemophagocytic - drug therapy; Lymphohistiocytosis, Hemophagocytic - mortality; Oncology; Pediatrics; Remission Induction; Retrospective Studies; Survival Rate; Japan; Epstein-Barr virus; Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis; hyperbilirubinemia; hyperferritinemia
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.24980

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. Pediatr Blood Cancer 2014;61:1257–1262. © 2014 Wiley Periodicals, Inc.