Fatal Epstein-Barr-virus-associated proliferation of donor B cells after treatment of acute graft-versus-host disease with a murine anti-T-cell antibody.
Two patients with acute leukemia were treated with chemoradiotherapy and allogeneic bone marrow transplantation. Despite the prophylactic use of methotrexate after grafting, both patients developed severe graft-versus-host disease that was refractory to treatment with methylprednisolone. The graft-versus-host disease was then treated with a monoclonal antibody, 64.1, that reacts with a p19 antigen on human T cells. The disease responded dramatically to this treatment, but both patients subsequently developed a fatal polyclonal lymphoproliferative disorder arising in donor-derived B cells. Hybridization studies showed Epstein-Barr virus in both tumors. The combined effect of severe end-stage graft-versus-host disease and potent immunosuppressive therapy probably resulted in a progressive immunodeficiency syndrome that abrogated the T-cell-mediated surveillance mechanism that normally modulates the proliferation of Epstein-Barr-virus-infected B lymphocytes.
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D001402:B-Lymphocytes / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006086:Graft vs Host Disease / Q000628:therapy*; D004854:Herpesvirus 4, Human / Q000032:analysis; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D014412:Tumor Virus Infections / Q000209:etiology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D004279:DNA, Viral