Nationwide Survey of Hemophagocytic Lymphohistiocytosis in Japan

  • Eiichi Ishii
  • Shouichi Ohga
  • Shinsaku Imashuku
  • Masaki Yasukawa
  • Hiroyuki Tsuda
  • Ikuo Miura
  • Ken Yamamoto
  • Hisanori Horiuchi
  • Kenzo Takada
  • Koichi Ohshima
  • Shigeo Nakamura
  • Naoko Kinukawa
  • Kazuo Oshimi
  • Keisei Kawa
Progress in Hematology


Hemophagocytic lymphohistiocytosis (HLH), a disorder of the mononuclear phagocyte system, can be classified into two distinct forms: primary HLH (FHL) and secondary HLH. To clarify the epidemiology and clinical outcome for each HLH subtype, we conducted a nationwide survey of HLH in Japan. Since 799 patients were diagnosed in 292 institutions of Japan between 2001 and 2005, the annual incidence of HLH was estimated as 1 in 800,000 per year. Among them, 567 cases were actually analyzed in this study. The most frequent subtype was Epstein-Barr virus (EBV)-associated HLH, followed by other infection- or lymphoma-associated HLH. Age distribution showed a peak of autoimmune disease- and infection-associated HLH in children, while FHL and lymphoma-associated HLH occurred almost exclusively in infants and the elderly, respectively. The 5-year overall survival rate exceeded 80% for patients with EBV- or other infection-associated HLH, was intermediate for those with FHL or B-cell lymphoma-associated HLH, and poor for those with T/NK cell lymphoma-associated HLH (<15%). Although this nationwide survey establishes the heterogeneous characteristics of HLH, the results should be useful in planning prospective studies to identify the most effective therapy for each HLH subtype.

Key words

Hemophagocytic lymphohistiocytosis Epstein-Barr virus lymphoma Autoimmune disease Prognostic factor 


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Copyright information

© The Japanese Society of Hematology 2007

Authors and Affiliations

  • Eiichi Ishii
    • 1
  • Shouichi Ohga
    • 2
  • Shinsaku Imashuku
    • 3
  • Masaki Yasukawa
    • 4
  • Hiroyuki Tsuda
    • 5
  • Ikuo Miura
    • 6
  • Ken Yamamoto
    • 7
  • Hisanori Horiuchi
    • 8
  • Kenzo Takada
    • 9
  • Koichi Ohshima
    • 10
  • Shigeo Nakamura
    • 11
  • Naoko Kinukawa
    • 12
  • Kazuo Oshimi
    • 13
  • Keisei Kawa
    • 14
  1. 1.Department of PediatricsEhime University Graduate School of MedicineEhimeJapan
  2. 2.Department of Pediatrics, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of PediatricsTakasago Seibu HospitalTakasagoJapan
  4. 4.Department of Bioregulatory MedicineEhime UniversityEhimeJapan
  5. 5.Division of Hematology/ImmunologyKumamoto City HospitalKumamotoJapan
  6. 6.Department of Hematology and OncologySt. Marianna University School of MedicineKawasakiJapan
  7. 7.Division of Molecular Population Genetics, Department of Molecular Genetics, Medical Institute of BioregulationKyushu UniversityFukuokaJapan
  8. 8.Department of Cardiovascular MedicineKyoto UniversityKyotoJapan
  9. 9.Department of VirologyHokkaido UniversityHokkaidoJapan
  10. 10.Department of PathologyKurume UniversityKurumeJapan
  11. 11.Department of PathologyNagoya UniversityNagoyaJapan
  12. 12.Division of Medical InformaticsKyushu UniversityFukuokaJapan
  13. 13.Department of Internal MedicineJuntendo UniversityTokyoJapan
  14. 14.Department of PediatricsOsaka Medical Center and Research Institute for Maternal and Child HealthOsakaJapan

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