title: HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis.
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.
authors.affiliation: Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. Jan-Inge.Henter@ki.se
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.forename: Annacarin
authors.initials: A
authors.lastname: Horne
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricó
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
authors.forename: Stephan
authors.initials: S
authors.lastname: Ladisch
authors.forename: Ken
authors.initials: K
authors.lastname: McClain
authors.forename: David
authors.initials: D
authors.lastname: Webb
authors.forename: Jacek
authors.initials: J
authors.lastname: Winiarski
authors.forename: Gritta
authors.initials: G
authors.lastname: Janka
mesh_terms: D003937:Diagnosis, Differential; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis* / Q000188:drug therapy / Q000628:therapy*; D017410:Practice Guidelines as Topic