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

TitleFatal Epstein-Barr-virus-associated proliferation of donor B cells after treatment of acute graft-versus-host disease with a murine anti-T-cell antibody
Publication TypeJournal Article
Year of Publication1984
AuthorsMartin PJ, Shulman HM, Schubach WH, Hansen JA, Fefer A, Miller G, Thomas ED
JournalAnn Intern Med
Volume101
Issue3
Pagination310 - 5
Date PublishedSep
ISSN0003-4819 (Print) 0003-4819 (Linking)
Accession Number6087703
KeywordsAdult, Animals, Antibodies, Monoclonal / *adverse effects, B-Lymphocytes / *pathology, Bone Marrow Transplantation, Child, Preschool, DNA, Viral / analysis, Female, Graft vs Host Disease / *therapy, Herpesvirus 4, Human / analysis, Humans, Leukemia, Myeloid, Acute / therapy, Lymphoproliferative Disorders / *etiology / pathology, Male, Mice, T-Lymphocytes / *immunology, Tumor Virus Infections / *etiology / pathology
Abstract

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.

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