INFUSIONS OF DONOR LEUKOCYTES TO TREAT EPSTEIN-BARR VIRUS-ASSOCIATED LYMPHOPROLIFERATIVE DISORDERS AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

Background. Lymphoma associated with Epstein-Barr virus (EBV) is a com plication of bone marrow transplantation that responds poorly to stand ard forms of therapy. The lymphoma is usually of donor origin. We hypo thesized that treatment with infusions of donor leukocytes, which cont ain cytotoxic T cells presensitized to EBV, might be an effective trea tment. Methods. We studied five patients in whom EBV-associated lympho proliferative disorders developed after they received a T-cell-deplete d allogeneic bone marrow transplant. Biopsy specimens were immunopheno typed, subjected to the polymerase chain reaction to determine the ori gin 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 wi th infusions of unirradiated donor leukocytes at doses calculated to p rovide approximately 1.0x10(6) CD3+ T cells per kilogram of body weigh t. 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 don or-cell origin. Evidence of clonality was found in two of the three sa mples adequate for study. EBV DNA was detected by the polymerase chain reaction in all five samples. In all five patients there were complet e pathological or clinical responses, The responses were first documen ted histologically within 8 to 21 days after infusion. Clinical remiss ions were achieved within 14 to 30 days after the infusions and were s ustained without further therapy in the three surviving patients for 1 0, 16, and 16 months. Conclusions. In a small number of patients, infu sions of unirradiated donor leukocytes were an effective treatment for EBV-associated lymphoproliferative disease that arose after allogenei c bone marrow transplantation.