Review of hemophagocytic lymphohistiocytosis (HLH) in children with focus on Japanese experiences

Eiichi Ishii, Shoichi Ohga, Shinsaku Imashuku, Nobuhiro Kimura, Ikuyo Ueda, Akira Morimoto, Ken Yamamoto, Masaki Yasukawa

Research output: Contribution to journalReview article

62 Citations (Scopus)

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever and hepatosplenomegaly associated with pancytopenia, hypertriglyceridemia and hypofibrinogenemia. Increased levels of cytokines and impaired natural killer activity are biological markers of HLH. HLH can be classified into two distinct forms, including primary HLH, also referred to as familial hemophagocytic lymphohistiocytosis (FHL), and secondary HLH. Although FHL is an autosomal recessive disorder typically occurring in infancy, it is important to clarify that the disease may also occur in older patients. It is now considered that FHL is a disorder of T-cell function; moreover, clonal proliferation of T lymphocytes is observed in a few FHL patients, and cytotoxicity of these T lymphocytes for target cells is usually impaired. In 1999, perforin gene (PRF1) mutation was identified as a cause of 20-30% of FHL (FHL2) cases. In Japan, two specific mutations of PRF1 were also detected. Furthermore, in 2003, MUNC13-4 mutations were identified in some non-FHL2 patients (FHL3). Identification of other genes responsible for remaining cases is a major concern. Hematopoietic stem cell transplantation (HSCT) has been established as the only accepted curative therapy for FHL. Thus, appropriate diagnosis and prompt treatment with HSCT are necessary for FHL patients. Genetic analysis for PRF1 and MUNC13-4 and functional assay of cytotoxic T lymphocytes are recommended to be performed in each patient. In those patients displaying impaired cytotoxic function but lacking genetic defects, samples should be employed for identification of unknown genes. In the near future, an entire pathogenesis should be clarified in order to establish appropriate therapies including immunotherapy, HSCT and gene therapy.

Original languageEnglish
Pages (from-to)209-223
Number of pages15
JournalCritical Reviews in Oncology/Hematology
Volume53
Issue number3
DOIs
Publication statusPublished - Jan 1 2005

Fingerprint

Hemophagocytic Lymphohistiocytosis
Hematopoietic Stem Cell Transplantation
T-Lymphocytes
Mutation
Genes
Perforin
Pancytopenia
Hypertriglyceridemia
Cytotoxic T-Lymphocytes
Cell- and Tissue-Based Therapy
Genetic Therapy
Immunotherapy
Japan
Fever

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Geriatrics and Gerontology

Cite this

Review of hemophagocytic lymphohistiocytosis (HLH) in children with focus on Japanese experiences. / Ishii, Eiichi; Ohga, Shoichi; Imashuku, Shinsaku; Kimura, Nobuhiro; Ueda, Ikuyo; Morimoto, Akira; Yamamoto, Ken; Yasukawa, Masaki.

In: Critical Reviews in Oncology/Hematology, Vol. 53, No. 3, 01.01.2005, p. 209-223.

Research output: Contribution to journalReview article

Ishii, Eiichi ; Ohga, Shoichi ; Imashuku, Shinsaku ; Kimura, Nobuhiro ; Ueda, Ikuyo ; Morimoto, Akira ; Yamamoto, Ken ; Yasukawa, Masaki. / Review of hemophagocytic lymphohistiocytosis (HLH) in children with focus on Japanese experiences. In: Critical Reviews in Oncology/Hematology. 2005 ; Vol. 53, No. 3. pp. 209-223.
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