title: Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes.
abstract: Cellular therapy of Epstein-Barr virus (EBV)(+) posttransplantation lymphoproliferative diseases (PTLD) in cord blood transplant (CBT) recipients is limited by lack of donor access and the donor's naive neonatal immune system. We therefore used partially human leukocyte antigen-matched third-party in vitro expanded EBV-specific cytotoxic T lymphocytes (CTLs) to treat 2 CBT recipients with life-threatening, donor-derived monoclonal EBV(+) diffuse large B-cell lymphomas with extranodal involvement developing in the context of graft-versus-host disease. Both patients had failed immunosuppression taper and Rituximab. After 5 and 9 infusions of 10(6) EBV-CTL/kg, respectively, each patient achieved a sustained complete remission without toxicity or graft-versus-host disease. Each is alive without recurrence at 20 and 15 months, respectively, post-EBV-PTLD diagnosis. This approach demonstrates the efficacy of using "off-the-shelf," virus-specific third-party CTLs restricted by human leukocyte antigens expressed by the tumor to treat otherwise lethal EBV-PTLD. Such therapy may also be applicable to the treatment of other infections and residual or recurrent malignancy after CBT.
authors.affiliation: Department of Medicine, Allogeneic Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. barkerj@mskcc.org
authors.forename: Juliet N
authors.initials: JN
authors.lastname: Barker
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Doubrovina
authors.forename: Craig
authors.initials: C
authors.lastname: Sauter
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Jaroscak
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Perales
authors.forename: Mikhail
authors.initials: M
authors.lastname: Doubrovin
authors.forename: Susan E
authors.initials: SE
authors.lastname: Prockop
authors.forename: Guenther
authors.initials: G
authors.lastname: Koehne
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
mesh_terms: D000328:Adult; D002648:Child; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects*; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000628:therapy; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008223:Lymphoma / Q000601:surgery; D016403:Lymphoma, Large B-Cell, Diffuse / Q000628:therapy* / Q000821:virology; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*
chemical_list: D006680:HLA Antigens
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