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
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
N Engl J Med. 1994 Apr 28;330(17):1185-91. doi: 10.1056/NEJM199404283301703.
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 x 10(6) 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.
与爱泼斯坦-巴尔病毒（EBV）相关的淋巴瘤是骨髓移植的一种并发症，对标准治疗形式反应不佳。这种淋巴瘤通常起源于供体。我们推测，输注含有对EBV预先致敏的细胞毒性T细胞的供体白细胞可能是一种有效的治疗方法。
我们研究了5例在接受T细胞去除的异基因骨髓移植后发生EBV相关淋巴增殖性疾病的患者。对活检标本进行免疫表型分析，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印迹分析来检测克隆性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，剂量经计算为每千克体重提供约1.0×10⁶个CD3⁺T细胞。
对所有5例患者的活检标本进行组织病理学检查，均显示为B细胞起源的单形性恶性淋巴瘤。4例可评估的标本均起源于供体细胞。在3例适合研究的样本中，有2例发现了克隆性证据。所有5个样本中均通过聚合酶链反应检测到EBV DNA。所有5例患者均有完全的病理或临床反应。反应首先在输注后8至21天通过组织学记录。输注后14至30天实现临床缓解，3例存活患者在未进一步治疗的情况下分别维持缓解10、16和16个月。
在少数患者中，输注未照射的供体白细胞是治疗异基因骨髓移植后出现的EBV相关淋巴增殖性疾病的有效方法。
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