Treatment of Newly Diagnosed HLH and Refractory Disease

  • Jan-Inge Henter
  • Rebecca A Marsh
  • Tatiana von Bahr Greenwood


To diagnose and treat a patient with hemophagocytic lymphohistiocytosis (HLH) is a challenge. Nevertheless, since the clinical course may be rapidly fatal and since the presentation may be variable, in particular for secondary HLH, it is important for clinicians in many medical fields to be aware of HLH and its treatment. Here, we review the treatment of patients with newly diagnosed HLH including therapy with corticosteroids, etoposide, cyclosporine A, and intravenous immunoglobulin (used in the HLH-94 and HLH-2004 protocols) as well as T-cell antibody-directed regimens with antithymocyte globulin (ATG) and alemtuzumab. We also report on anti-infectious and supportive therapy, prognostic factors, as well as the challenging treatment of secondary HLH, including infection-associated HLH, malignancy-associated HLH, and rheuma-/autoimmune-associated HLH. Finally, a literature review on salvage therapy for patients that fail to respond to standard HLH treatment is presented, including treatments with ATG, anakinra, and alemtuzumab.


Familial hemophagocytic lymphohistiocytosis Hemophagocytic lymphohistiocytosis Epstein-Barr virus Treatment Etoposide Dexamethasone Cyclosporine A Antithymocyte globulin Refractory disease Alemtuzumab 



Antithymocyte globulin


Cyclosporine A


Doxorubicin, etoposide, and methylprednisolone


Epstein-Barr virus


Familial hemophagocytic lymphohistiocytosis


Hemophagocytic lymphohistiocytosis






Intravenous immunoglobulin


Macrophage activation syndrome


Hematopoietic stem cell transplantation


Secondary HLH


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Jan-Inge Henter
    • 1
  • Rebecca A Marsh
    • 2
  • Tatiana von Bahr Greenwood
    • 1
  1. 1.Childhood Cancer Research Unit, Department of Women’s and Children’s HealthKarolinska Institutet, and Theme of Children’s and Women’s Health, Karolinska University HospitalStockholmSweden
  2. 2.Division of Bone Marrow Transplantation and Immune DeficiencyCincinnati Children’s Hospital Medical CenterCincinnatiUSA

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