Haemophagocytic lymphohistiocytosis (HLH) comprises a rare group of disorders typified by activation of CD8+ T cells and macrophages and secretion of high levels of pro-inflammatory cytokines (Lykens et al, 2011; Janka, 2012; Risma & Jordan, 2012). HLH occurs as a hereditary condition caused by germline mutations that impair lymphocyte cytotoxic function or as a nonhereditary disorder triggered by infection, malignancy or autoimmune disease (Coffey et al, 1998; Nichols et al, 1998; Stepp et al, 1999; Feldmann et al, 2003; Zur Stadt et al, 2005, 2009; Rigaud et al, 2006; Cote et al, 2009; Janka, 2012). Currently, a two-tiered approach is used to treat HLH: chemo-immunotherapeutic agents are administered to dampen inflammation and targeted therapies are given to eliminate HLH trigger(s) (Janka, 2012).
Epstein–Barr virus (EBV) is a common trigger of HLH, particularly in Asian individuals (Kawaguchi et al, 1993; Imashuku, 2002; Yachie et al, 2003) and in patients with congenital or acquired immunodeficiencies (McClain et al, 1988; Pasic et al, 2003; Rezaei et al, 2011). EBV is poorly responsive to antiviral agents; however, it resides in B lymphocytes, which can be rapidly depleted using the B cell-targeting monoclonal antibody rituximab. Based on its efficacy in lowering disease burden in patients with B-lymphoproliferative disorders (DiNardo & Tsai, 2010; Maloney, 2012), some investigators are using rituximab to treat EBV-HLH. It is not known whether this is an effective strategy for this disorder.
To understand current practice and prepare for the possible incorporation of rituximab into future HLH protocols, we performed this retrospective investigation, which describes 42 patients with EBV-induced disease, who were treated with regimens containing rituximab, steroids, etoposide and/or ciclosporin. Rituximab-containing regimens improved clinical status in most patients, exhibited no toxicities beyond those normally encountered and significantly reduced EBV load and serum ferritin levels. These data suggest that rituximab can be safely added to standard therapies and provide the evidence needed to move forward with a prospective clinical trial.