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

Academic Article


  • 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.
  • Published In


  • Epstein-Barr virus, haemophagocytic lymphohistiocytosis, macrophage activation syndrome, rituximab, x-linked lymphoproliferative disease, Adolescent, Adult, Aged, Antibodies, Monoclonal, Murine-Derived, Antiviral Agents, Child, Child, Preschool, Drug Administration Schedule, Drug Evaluation, Drug Therapy, Combination, Epstein-Barr Virus Infections, Female, Herpesvirus 4, Human, Humans, Immunologic Factors, Lymphohistiocytosis, Hemophagocytic, Male, Middle Aged, Prognosis, Retrospective Studies, Rituximab, Survival Analysis, Treatment Outcome, Viral Load, Young Adult
  • Digital Object Identifier (doi)

    Author List

  • Chellapandian D; Das R; Zelley K; Wiener SJ; Zhao H; Teachey DT; Nichols KE; EBV-HLH Rituximab Study Group
  • Start Page

  • 376
  • End Page

  • 382
  • Volume

  • 162
  • Issue

  • 3