Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation Journal Article


Authors: Papadopoulos, E. B.; Ladanyi, M.; Emanuel, D.; Mackinnon, S.; Boulad, F.; Carabasi, M. H.; Castro-Malaspina, H.; Childs, B. H.; Gillio, A. P.; Small, T. N.; Young, J. W.; Kernan, N. A.; O'Reilly, R. J.
Article Title: Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation
Abstract: Lymphoma associated with Epstein-Barr virus (EBV) is a complication of bone marrow transplantation that responds poorly to standard forms of therapy. The lymphoma is usually of donor origin. We hypothesized that treatment with infusions of donor leukocytes, which contain cytotoxic T cells presensitized to EBV, might be an effective treatment. We studied five patients in whom EBV-associated lymphoproliferative disorders developed after they received a T-cell-depleted allogeneic bone marrow transplant. Biopsy specimens were immunophenotyped, subjected to the polymerase chain reaction to determine the origin of the lymphoma (donor or host) and to detect the presence of EBV, and analyzed by Southern blotting for the presence of the clonal EBV genome and immunoglobulin-gene rearrangement. Patients were treated with infusions of unirradiated donor leukocytes at doses calculated to provide approximately 1.0 × 106 CD3+ T cells per kilogram of body weight. Histopathological examination of biopsy specimens from all five patients demonstrated monomorphic, malignant lymphomas of B-cell origin. Each of the four specimens that could be evaluated was of donor-cell origin. Evidence of clonality was found in two of the three samples adequate for study. EBV DNA was detected by the polymerase chain reaction in all five samples. In all five patients there were complete pathological or clinical responses. The responses were first documented histologically within 8 to 21 days after infusion. Clinical remissions were achieved within 14 to 30 days after the infusions and were sustained without further therapy in the three surviving patients for 10, 16, and 16 months. In a small number of patients, infusions of unirradiated donor leukocytes were an effective treatment for EBV-associated lymphoproliferative disease that arose after allogeneic bone marrow transplantation. © 1994, Massachusetts Medical Society. All rights reserved.
Keywords: adult; clinical article; middle aged; leukemia; histopathology; polymerase chain reaction; disease association; allogenic bone marrow transplantation; b cell lymphoma; tissue donors; immunotherapy; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; remission; immunophenotyping; dna, viral; tumor virus infections; bone marrow transplantation; leukocyte; burkitt lymphoma; epstein barr virus; cell transfer; virus detection; herpesvirus 4, human; southern blotting; herpesviridae infections; humans; human; male; female; priority journal; article
Journal Title: New England Journal of Medicine
Volume: 330
Issue: 17
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 1994-04-28
Start Page: 1185
End Page: 1191
Language: English
DOI: 10.1056/nejm199404283301703
PROVIDER: scopus
PUBMED: 8093146
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Nancy Kernan
    512 Kernan
  2. Trudy Small
    234 Small
  3. Farid Boulad
    329 Boulad
  4. Barrett H Childs
    74 Childs
  5. Marc Ladanyi
    1326 Ladanyi
  6. James W Young
    318 Young
  7. Richard O'Reilly
    747 O'Reilly
  8. Alfred P. Gillio
    89 Gillio
  9. David J. Emanuel
    28 Emanuel