title: Treatment of Epstein Barr virus-induced haemophagocytic lymphohistiocytosis with rituximab-containing chemo-immunotherapeutic regimens.
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.
authors.affiliation: Department of Pediatrics, Einstein Medical Center, Philadelphia, PA, USA.
authors.forename: DeepakBabu
authors.initials: D
authors.lastname: Chellapandian
authors.forename: Rupali
authors.initials: R
authors.lastname: Das
authors.forename: Kristin
authors.initials: K
authors.lastname: Zelley
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Wiener
authors.forename: Huaqing
authors.initials: H
authors.lastname: Zhao
authors.forename: David T
authors.initials: DT
authors.lastname: Teachey
authors.forename: Kim E
authors.initials: KE
authors.lastname: Nichols
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004341:Drug Evaluation / Q000379:methods; D004359:Drug Therapy, Combination; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000188:drug therapy* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D007155:Immunologic Factors; D000069283:Rituximab
keywords: Epstein-Barr virus; haemophagocytic lymphohistiocytosis; macrophage activation syndrome; rituximab; x-linked lymphoproliferative disease