HLH‐2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis

Pediatric Blood & CancerVolume 48, Issue 2 p. 124-131 Review Article HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis Jan-Inge Henter MD, PhD, Corresponding Author Jan-Inge Henter MD, PhD Jan-Inge.Henter@ki.se Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, SwedenChildhood Cancer Research Unit, Karolinska Hospital Q6:05, SE-171 76 Stockholm, Sweden.===Search for more papers by this authorAnnaCarin Horne MD, AnnaCarin Horne MD Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorMaurizio Aricó MD, Maurizio Aricó MD Pediatric Hematology/Oncology, Ospetale dei Bambini, Palermo, ItalySearch for more papers by this authorR. Maarten Egeler MD, PhD, R. Maarten Egeler MD, PhD Department of Pediatrics IHOBA, Leiden University Medical Center, Leiden, The NetherlandsSearch for more papers by this authorAlexandra H. Filipovich MD, Alexandra H. Filipovich MD Children's Hospital Medical Center, Cincinnati OhioSearch for more papers by this authorShinsaku Imashuku MD, Shinsaku Imashuku MD Department of Pediatrics, Takasago-Seibu Hospital, JapanSearch for more papers by this authorStephan Ladisch MD, Stephan Ladisch MD Children's Research Institute, Washington, District of ColumbiaSearch for more papers by this authorKen McClain MD, PhD, Ken McClain MD, PhD Pediatric Hematology/Oncology, Texas Children's Hospital, Houston, TexasSearch for more papers by this authorDavid Webb MD, David Webb MD Great Ormond Street Hospital, London, UKSearch for more papers by this authorJacek Winiarski MD, PhD, Jacek Winiarski MD, PhD Department of Pediatrics, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorGritta Janka MD, PhD, Gritta Janka MD, PhD Department of Hematology Oncology, Children's University Hospital, Hamburg, GermanySearch for more papers by this author Jan-Inge Henter MD, PhD, Corresponding Author Jan-Inge Henter MD, PhD Jan-Inge.Henter@ki.se Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, SwedenChildhood Cancer Research Unit, Karolinska Hospital Q6:05, SE-171 76 Stockholm, Sweden.===Search for more papers by this authorAnnaCarin Horne MD, AnnaCarin Horne MD Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorMaurizio Aricó MD, Maurizio Aricó MD Pediatric Hematology/Oncology, Ospetale dei Bambini, Palermo, ItalySearch for more papers by this authorR. Maarten Egeler MD, PhD, R. Maarten Egeler MD, PhD Department of Pediatrics IHOBA, Leiden University Medical Center, Leiden, The NetherlandsSearch for more papers by this authorAlexandra H. Filipovich MD, Alexandra H. Filipovich MD Children's Hospital Medical Center, Cincinnati OhioSearch for more papers by this authorShinsaku Imashuku MD, Shinsaku Imashuku MD Department of Pediatrics, Takasago-Seibu Hospital, JapanSearch for more papers by this authorStephan Ladisch MD, Stephan Ladisch MD Children's Research Institute, Washington, District of ColumbiaSearch for more papers by this authorKen McClain MD, PhD, Ken McClain MD, PhD Pediatric Hematology/Oncology, Texas Children's Hospital, Houston, TexasSearch for more papers by this authorDavid Webb MD, David Webb MD Great Ormond Street Hospital, London, UKSearch for more papers by this authorJacek Winiarski MD, PhD, Jacek Winiarski MD, PhD Department of Pediatrics, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorGritta Janka MD, PhD, Gritta Janka MD, PhD Department of Hematology Oncology, Children's University Hospital, Hamburg, GermanySearch for more papers by this author First published: 25 August 2006 https://doi.org/10.1002/pbc.21039Citations: 2,881Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract In HLH-94, the first prospective international treatment study for hemophagocytic lymphohistiocytosis (HLH), diagnosis was based on five criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis). In HLH-2004 three additional criteria are introduced; low/absent NK-cell-activity, hyperferritinemia, and high-soluble interleukin-2-receptor levels. Altogether five of these eight criteria must be fulfilled, unless family history or molecular diagnosis is consistent with HLH. HLH-2004 chemo-immunotherapy includes etoposide, dexamethasone, cyclosporine A upfront and, in selected patients, intrathecal therapy with methotrexate and corticosteroids. Subsequent hematopoietic stem cell transplantation (HSCT) is recommended for patients with familial disease or molecular diagnosis, and patients with severe and persistent, or reactivated, disease. In order to hopefully further improve diagnosis, therapy and biological understanding, participation in HLH studies is encouraged. Pediatr Blood Cancer 2007;48:124–131. © 2006 Wiley-Liss, Inc. Citing Literature Volume48, Issue2February 2007Pages 124-131 RelatedInformation