title: Use of rituximab and irradiated donor-derived lymphocytes to control Epstein-Barr virus-associated lymphoproliferation in patients undergoing related haplo-identical stem cell transplantation.
abstract: Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) is an uncommon but potentially fatal complication of allogeneic stem cell transplantation. We report here two patients who underwent T cell-depleted mismatched-related stem cell transplantation for hematologic malignancies and required aggressive post-transplant immunosuppression for graft-versus host disease (GVHD). Both patients subsequently developed markedly elevated EBV-DNA titers in association with monoclonal, light chain-restricted B cell populations in the blood. Although immunosuppressive medications were rapidly tapered, neither patient could receive potentially curative therapy with unmanipulated donor-derived lymphocyte infusions (DLI) because of the substantial risk of severe GVHD. Therefore, both patients received repeated courses of rituximab, an anti-CD20 monoclonal antibody, in combination with irradiated DLI. This therapeutic strategy resulted in normalization of the elevated EBV-DNA titers and disappearance of the monoclonal B cell populations. Our results suggest that rituximab and possibly irradiated DLI played an important role in controlling early EBV-LPD in these two patients and may be an effective alternative therapeutic strategy for patients who develop EBV-LPD post transplant and are unable to receive unmanipulated DLI.
authors.affiliation: Blood and Marrow Transplant Program, Yale University School of Medicine, New Haven, Connecticut 06520-8032, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: McGuirk
authors.forename: S
authors.initials: S
authors.lastname: Seropian
authors.forename: G
authors.initials: G
authors.lastname: Howe
authors.forename: B
authors.initials: B
authors.lastname: Smith
authors.forename: L
authors.initials: L
authors.lastname: Stoddart
authors.forename: D L
authors.initials: DL
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000956:Antigens, Viral / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016913:Blood Component Transfusion; D001782:Blood Donors; D004279:DNA, Viral / Q000097:blood; D006086:Graft vs Host Disease / Q000188:drug therapy; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D008214:Lymphocytes / Q000276:immunology / Q000528:radiation effects* / Q000821:virology*; D008232:Lymphoproliferative Disorders / Q000821:virology*; D008297:Male; D016133:Polymerase Chain Reaction; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000956:Antigens, Viral; D000970:Antineoplastic Agents; D004279:DNA, Viral; D000069283:Rituximab