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

• Published in: British journal of haematology Vol. 162; no. 3; pp. 376 - 382
• Main Authors: Chellapandian, DeepakBabu, Das, Rupali, Zelley, Kristin, Wiener, Susan J., Zhao, Huaqing, Teachey, David T., Nichols, Kim E., Hale, Gregory, Minkov, Milen, Karlhuber, Susanne, Weinstein, Joanna L., Weitzman, Sheila, Moshous, Despina, Fischer, Alain, Jeng, Michael, Henry, Michael, Haupt, Riccardo, Svahn, Joanna, Zapotocka, Ester, Wolfson, Julie, Yacobovich, Joanne, Van Laar, Jan A.M., Talano, Julie, Astigarraga, Itziar, Beutel, Karin, Berglöf, Elisabet, Henter, Jan‐Inge, Imashuku, Shinsaku, Ho, Marco Hok‐kung, Fraser, Chris, Greene Welch, Jennifer, Kitchen, Brenda, Jasty, Rama, Degar, Barbara A., Gunnes, Maria Winther, McMahon, Corrina, Garrington, Timothy, Filipovich, Alexandra H., Jordan, Michael B., Bleesing, Jacob J., Marsh, Rebecca A.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.08.2013
• Subjects: 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; Biological and medical sciences; Child; Child, Preschool; Drug Administration Schedule; Drug Evaluation - methods; Drug Therapy, Combination; Epstein-Barr virus; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - drug therapy; Epstein-Barr Virus Infections - virology; Female; haemophagocytic lymphohistiocytosis; Hematologic and hematopoietic diseases; 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; macrophage activation syndrome; Male; Medical sciences; Middle Aged; Other diseases. Hematologic involvement in other diseases; Prognosis; Retrospective Studies; Rituximab; Survival Analysis; Treatment Outcome; Tumors; Viral Load - drug effects; x‐linked lymphoproliferative disease; Young Adult; Antineoplastic agent; Hemopathy; Epstein Barr virus; Monoclonal antibody; Hemophagocytic lymphohistiocytosis; Cancerology; Immunotherapy; Epstein-Barr virus; Gammaherpesvirinae; Immunopathology; Hematology; Herpesviridae; Rituximab; haemophagocytic lymphohistiocytosis; macrophage activation syndrome; Histiocytosis; Immune deficiency; x-linked lymphoproliferative disease; Genetic disease; Infection; Virus; Hemophagocytic syndrome; Treatment; Viral disease; Therapeutic protocol; Duncan disease; rituximab
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.12386

Summary 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/m2. 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.