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Previous Volume 330:1185-1191 April 28, 1994 Number 17 Next

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ABSTRACT

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 10⁶ 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.

Source Information

From the Bone Marrow Transplantation Service of the Departments of Medicine (E.B.P., S.M., M.H.C., H.C.-M., B.H.C., J.W.Y.) and Pediatrics (D.E., F.B., A.P.G., T.N.S., N.A.K., R.J.O.) and the Department of Pathology (M.L.), Memorial Sloan-Kettering Cancer Center, New York.

Address reprint requests to Dr. Papadopoulos at Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.

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Donor T Cells to Treat EBV-Associated Lymphoma
Heslop H. E., Brenner M. K., Rooney C. M., Papadopoulos E. B., O'Reilly R. J.
Extract | Full Text  
N Engl J Med 1994; 331:679-680, Sep 8, 1994. Correspondence

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