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Recommendations for the management of hemophagocytic lymphohistiocytosis in adults

Paul La Rosée, AnnaCarin Horne, Melissa Hines, Tatiana von Bahr Greenwood, Rafal Machowicz, Nancy Berliner, Sebastian Birndt, Juana Gil-Herrera, Michael Girschikofsky, Michael B. Jordan, Ashish Kumar, Jan A. M. van Laar, Gunnar Lachmann, Kim E. Nichols, Athimalaipet V. Ramanan, Yini Wang, Zhao Wang, Gritta Janka and Jan-Inge Henter

Abstract

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.

  • Submitted December 31, 2018.
  • Accepted April 12, 2019.
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