Rooney C M, Smith C A, Ng C Y, Loftin S, Li C, Krance R A, Brenner M K, Heslop H E
Department of Virology and Molecular Biology, St Jude Children's Research Hospital, Memphis, TN 38105.
Lancet. 1995 Jan 7;345(8941):9-13. doi: 10.1016/s0140-6736(95)91150-2.
Reactivation of Epstein-Barr virus (EBV) after bone-marrow transplantation leads in many cases to lymphoproliferative disease that responds poorly to standard therapy and is usually fatal. To prevent or control this complication, we prepared EBV-specific cytotoxic T-lymphocyte (CTL) lines from donor leucocytes and infused them into ten allograft recipients. Three of the patients had shown signs of EBV reactivation, with or without overt lymphoproliferation, and the others received CTL infusions as prophylaxis. No patient developed any complication that could be attributed to the CTL infusions. In the three patients with EBV reactivation, EBV DNA concentrations (measured by semiquantitative polymerase chain reaction [PCR]), which had increased 1000-fold or more, returned to the control range within 3-4 weeks of immunotherapy. The most striking consequence was the resolution of immunoblastic lymphoma in a 17-year-old patient who received four CTL infusions (two 1 x 10(7)/m2 and two 5 x 10(7)/m2). Because the CTL had been genetically marked before infusion, we were able to show by PCR analysis that they persisted for 10 weeks after administration. EBV-specific donor-type T-cell lines seem to offer safe and effective therapy for control of EBV-associated lymphoproliferation.
骨髓移植后爱泼斯坦-巴尔病毒（EBV）再激活在许多情况下会导致淋巴增殖性疾病，这种疾病对标准治疗反应不佳，通常是致命的。为了预防或控制这种并发症，我们从供体白细胞中制备了EBV特异性细胞毒性T淋巴细胞（CTL）系，并将其输注给10名同种异体移植受者。其中3例患者已出现EBV再激活迹象，伴有或不伴有明显的淋巴增殖，其他患者接受CTL输注作为预防措施。没有患者出现任何可归因于CTL输注的并发症。在3例EBV再激活患者中，通过半定量聚合酶链反应（PCR）测量的EBV DNA浓度增加了1000倍或更多，在免疫治疗的3 - 4周内恢复到对照范围。最显著的结果是一名17岁患者的免疫母细胞淋巴瘤得到缓解，该患者接受了4次CTL输注（两次1×10⁷/m²和两次5×10⁷/m²）。由于CTL在输注前已进行基因标记，我们能够通过PCR分析表明它们在给药后持续存在10周。EBV特异性供体型T细胞系似乎为控制EBV相关的淋巴增殖提供了安全有效的治疗方法。
