Hemophagocytic Lymphohistiocytosis Associated with Malignancies and with Epstein-Barr Virus

  • Kai Lehmberg
  • Fumihiro Ochi
  • Kim E. Nichols
  • Eiichi Ishii


Hemophagocytic lymphohistiocytosis (HLH) represents an often life-threatening syndrome associated with the uncontrolled activation of immune cells and the overproduction of pro-inflammatory cytokines. HLH can occur as the result of several underlying conditions in which there is excess stimulation of the immune system, in combination with inadequate downregulation of the immune response. Among the stimuli commonly associated with HLH are underlying malignancies, most often lymphomas, and certain viruses, including Epstein-Barr virus (EBV), a member of the herpesvirus family. In recent years, increased awareness has led to improved recognition as well as research into these as yet poorly understood disorders. We discuss current insights into the clinical manifestations, prognostic features, biology, and treatment approaches for malignancy- and EBV-associated HLH.


Hemophagocytic lymphohistiocytosis Hemophagocytic syndrome Macrophage activation syndrome Epstein-Barr virus T cell lymphoma Diffuse large B cell lymphoma Hodgkin lymphoma Etoposide Clonality Rituximab 



Chronic active EBV infection




Cytotoxic T cells


Epstein-Barr nuclear antigen


Epstein-Barr virus


Familial HLH


Fulminant mononucleosis


Human immune deficiency virus


Hemophagocytic lymphohistiocytosis


Hematopoietic stem cell transplantation




Infectious mononucleosis


Inducible T cell kinase


Myeloablative conditioning


Magnesium transporter 1


Magnetic resonance imaging


Natural killer


Peripheral blood mononuclear cells


Post-transplantation lymphoproliferative disorder


Reduced intensity conditioning


Soluble IL2 receptor


Total body irradiation


T cell receptor


Transforming growth factor


Unrelated donor cord blood transplantation


Virus capsid antigen


X-linked lymphoproliferative disease


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Kai Lehmberg
    • 1
  • Fumihiro Ochi
    • 2
  • Kim E. Nichols
    • 3
  • Eiichi Ishii
    • 2
  1. 1.Department of Pediatric Hematology and OncologyUniversity Medical Center Hamburg EppendorfHamburgGermany
  2. 2.Department of PediatricsEhime University Graduate School of MedicineToonJapan
  3. 3.Department of OncologySt. Jude Children’s Research HospitalMemphisUSA

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