HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis.
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.
Henter
Jan-Inge
JI
Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. Jan-Inge.Henter@ki.se
Horne
Annacarin
A
Aricó
Maurizio
M
Egeler
R Maarten
RM
Filipovich
Alexandra H
AH
Imashuku
Shinsaku
S
Ladisch
Stephan
S
McClain
Ken
K
Webb
David
D
Winiarski
Jacek
J
Janka
Gritta
G
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