INFUSIONS OF DONOR LEUKOCYTES TO TREAT EPSTEIN-BARR VIRUS-ASSOCIATED LYMPHOPROLIFERATIVE DISORDERS AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION
INFUSIONS OF DONOR LEUKOCYTES TO TREAT EPSTEIN-BARR VIRUS-ASSOCIATED LYMPHOPROLIFERATIVE DISORDERS AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION
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DOI：
10.1056/nejm199404283301703
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发表时间：
1994-04-28
影响因子：
158.5
通讯作者：
OREILLY, RJ
中科院分区：
文献类型：
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作者：
PAPADOPOULOS, EB;LADANYI, M;OREILLY, RJ
背景与EB病毒（EBV）相关的淋巴瘤是骨髓移植的并发症，对标准形式的治疗反应不佳。淋巴瘤通常是供体来源的。我们假设输注供体白细胞（其中含有对EBV致敏的细胞毒性T细胞）治疗可能是一种有效的治疗方法。我们研究了5例接受去除T细胞的异基因骨髓移植后发生EBV相关淋巴组织增生性疾病的患者。活检标本进行免疫分型，进行聚合酶链反应，以确定淋巴瘤的起源（供体或宿主），并检测EBV的存在，并通过Southern印迹分析克隆EBV基因组和免疫球蛋白基因重排的存在。患者接受未照射的供体白细胞输注治疗，剂量计算为每公斤体重提供约1.0x10（6）CD 3 + T细胞。所有5例患者的活检标本的组织学检查均显示为单形性B细胞来源的恶性淋巴瘤。可以评价的四个标本均为供体细胞来源。在足以进行研究的三个样品中的两个中发现了克隆性的证据。聚合酶链反应检测EB病毒DNA在所有五个样本。在所有5名患者中，均存在完全的病理学或临床反应。在输注后8至21天内首次在组织学上记录反应。在输注后14 - 30天内达到临床缓解，3例存活患者在10、16和16个月内未接受进一步治疗。在少数患者中，输注未经辐照的供体白细胞是异基因骨髓移植后出现的EBV相关淋巴组织增生性疾病的有效治疗方法。
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 1.0x10(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.