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Blood. 2019 Jun 6;133(23):2465-2477. doi: 10.1182/blood.2018894618. Epub 2019 Apr 16.

Recommendations for the management of hemophagocytic lymphohistiocytosis in adults.

Author information

Klinik für Innere Medizin II, Schwarzwald-Baar-Klinikum, Villingen-Schwenningen, Germany.
Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, and Theme of Children's and Women's Health, Karolinska University Hospital, Stockholm, Sweden.
Division of Critical Care Medicine, St. Jude Children's Research Hospital, Memphis, TN.
Department of Hematology, Oncology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.
Division of Immunology, Hospital General Universitario and Health Research Institute Gregorio Marañón, Madrid, Spain.
Internal Medicine I, Ordensklinikum Linz Elisabethinen, Linz, Austria.
Division of Immunobiology and Bone Marrow Transplantation and.
Division of Immune Deficiency, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH.
Section of Clinical Immunology, Department of Internal Medicine and Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Anesthesiology and Operative Intensive Care Medicine (Charité Campus Mitte, Charité Virchow-Klinikum), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Division of Cancer Predisposition, St. Jude Children's Research Hospital, Memphis, TN.
University Hospitals Bristol National Health Service Foundation Trust and Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; and.
Clinic of Pediatric Hematology and Oncology, University Medical Center Eppendorf, Hamburg, Germany.


Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic T cells. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults. Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory/autoimmune disorders, in which case it is called macrophage activation syndrome (MAS; or MAS-HLH). Most information on the diagnosis and treatment of HLH comes from the pediatric literature. Although helpful in some adult cases, this raises several challenges. For example, the HLH-2004 diagnostic criteria developed for children are commonly applied but are not validated for adults. Another challenge in HLH diagnosis is that patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome. Treatment algorithms targeting hyperinflammation are frequently based on pediatric protocols, such as HLH-94 and HLH-2004, which may result in overtreatment and unnecessary toxicity in adults. Therefore, dose reductions, individualized tailoring of treatment duration, and an age-dependent modified diagnostic approach are to be considered. Here, we present expert opinions derived from an interdisciplinary working group on adult HLH, sponsored by the Histiocyte Society, to facilitate knowledge transfer between physicians caring for pediatric and adult patients with HLH, with the aim to improve the outcome for adult patients affected by HLH.

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