HLH‐2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis

TLDR

HLH‑94 diagnosis relies on five criteria: fever, splenomegaly, bicytopenia, hypertriglyceridemia or hypofibrinogenemia, and hemophagocytosis. HLH‑2004 seeks to enhance diagnosis, therapy, and biological insight by adding three new criteria and encouraging study participation. The guideline requires fulfillment of five of eight criteria—fever, splenomegaly.

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.