Treatment of Epstein Barr virus-induced haemophagocytic lymphohistiocytosis with rituximab-containing chemo-immunotherapeutic regimens

Br J Haematol. 2013 Aug;162(3):376-82. doi: 10.1111/bjh.12386. Epub 2013 May 21.

Abstract

Haemophagocytic lymphohistiocytosis (HLH) is a life threatening complication of Epstein-Barr virus (EBV) infection. The anti-CD20 antibody rituximab depletes B cells, leading to improved outcomes for patients with EBV-associated B-lymphoproliferative disorders. To gather data on the use of rituximab in EBV-HLH, we performed a retrospective investigation involving 42 EBV-HLH patients who had received treatment with rituximab-containing regimens. On average, patients received 3 rituximab infusions (range 1-10) at a median dose of 375 mg/m(2) . In all patients, rituximab was administered with other HLH-directed medications, including steroids, etoposide and/or ciclosporin. Rituximab-containing regimens appeared well tolerated and improved clinical status in 43% of patients. Examination of laboratory data obtained prior to and within 2-4 weeks after the first rituximab dose revealed significant reductions in EBV load (median load pre-rituximab: 114,200 copies/ml, median post-rituximab: 225 copies/ml, P = 0.0001) and serum ferritin levels (median ferritin pre-rituximab: 4260 μg/l, median post-rituximab: 1149 μg/l, P = 0.001). Thus, when combined with conventional HLH-directed therapies, rituximab improves symptoms, reduces viral load and diminishes inflammation. These data support the incorporation of rituximab into future prospective clinical trials for patients with EBV-HLH.

Keywords: Epstein-Barr virus; haemophagocytic lymphohistiocytosis; macrophage activation syndrome; rituximab; x-linked lymphoproliferative disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antiviral Agents / therapeutic use
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Drug Evaluation / methods
  • Drug Therapy, Combination
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / drug therapy
  • Epstein-Barr Virus Infections / virology
  • Female
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Lymphohistiocytosis, Hemophagocytic / drug therapy*
  • Lymphohistiocytosis, Hemophagocytic / virology*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Rituximab
  • Survival Analysis
  • Treatment Outcome
  • Viral Load / drug effects
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antiviral Agents
  • Immunologic Factors
  • Rituximab