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Infusions of Donor Leukocytes to Treat Epstein-Barr Virus-Associated Lymphoproliferative Disorders after Allogeneic Bone Marrow Transplantation
Open accessAbstract
BACKGROUND: 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. METHODS: 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 x 10(6) CD3+ T cells per kilogram of body weight. RESULTS: 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. CONCLUSIONS: 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.
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Cited by
Walter, E. A., Greenberg, P. D., Gilbert, M. J., Finch, R. J., Watanabe, K. S., Thomas, E. D., & Riddell, S. R. (1995) · New England Journal of Medicine · doi:10.1056/nejm199510193331603 · Cited by 1,771
Einsele, H., Roosnek, E., Rufer, N., Sinzger, C., Riegler, S., Löffler, J., Grigoleit, U., Moris, A., Rammensee, H.-G., Kanz, L., et al. (2002) · Blood · doi:10.1182/blood.v99.11.3916 · Cited by 699
Brentjens, R. J., Latouche, J.-B., Santos, E., Marti, F., Gong, M. C., Lyddane, C., King, P. D., Larson, S., Weiss, M., Rivière, I., et al. (2003) · Nature Medicine · doi:10.1038/nm827 · Cited by 669
A Re-Evaluation of the Frequency of CD8+ T Cells Specific for EBV in Healthy Virus Carriers
Tan, L. C., Gudgeon, N., Annels, N. E., Hansasuta, P., O’Callaghan, C. A., Rowland-Jones, S., McMichael, A. J., Rickinson, A. B., & Callan, M. F. C. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.3.1827 · Cited by 499
Cobbold, M., Khan, N., Pourgheysari, B., Tauro, S., McDonald, D., Osman, H., Assenmacher, M., Billingham, L., Steward, C., Crawley, C., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20040613 · Cited by 480
Metadata
- 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.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1994-04-28
- Volume
- 330
- Issue
- 17
- Pages
- 1185-1191
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1977635228
- Cited by
- 1,043
- References
- 0
- FWCI
- 20.95
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Infusions of Donor Leukocytes to Treat Epstein-Barr Virus-Associated Lymphoproliferative Disorders after Allogeneic Bone Marrow Transplantation. https://app.cochat.ai/papers/10.1056/nejm199404283301703
- The paper
- 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. (1994). Infusions of Donor Leukocytes to Treat Epstein-Barr Virus-Associated Lymphoproliferative Disorders after Allogeneic Bone Marrow Transplantation. New England Journal of Medicine. https://doi.org/10.1056/nejm199404283301703
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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