Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes
Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes
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DOI：
10.1182/blood-2010-04-281873
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发表时间：
2010-12-02
期刊：
影响因子：
20.3
通讯作者：
O'Reilly, Richard J.
中科院分区：
文献类型：
--
作者：
Barker, Juliet N.;Doubrovina, Ekaterina;O'Reilly, Richard J.
脐带血移植（CBT）受者中Epstein-Barr病毒（EBV）（+）移植后淋巴组织增生性疾病（PTLD）的细胞治疗受到缺乏供体途径和供体的幼稚新生儿免疫系统的限制。因此，我们使用部分人类白细胞抗原匹配的第三方体外扩增的EBV特异性细胞毒性T淋巴细胞（CTL）治疗2例在移植物抗宿主病背景下发生的危及生命的供体来源单克隆EBV（+）弥漫性大B细胞淋巴瘤的CBT受者。两名患者均失败免疫抑制锥度和利妥昔单抗。分别输注5次和9次106 EBV-CTL/kg后，每例患者均获得持续完全缓解，无毒性或移植物抗宿主病。在EBV-PTLD诊断后的20个月和15个月，每个人都活着，没有复发。这种方法证明了使用“现成的”病毒特异性第三方CTL（其受肿瘤表达的人白细胞抗原限制）治疗其他致命EBV-PTLD的功效。这种疗法也可适用于治疗其他感染和CBT后残留或复发的恶性肿瘤。（血。2010;116（23）：5045-5049）
Cellular therapy of Epstein-Barr virus (EBV)(+) posttransplantation lymphoproliferative diseases (PTLD) in cord blood transplant (CBT) recipients is limited by lack of donor access and the donor's naive neonatal immune system. We therefore used partially human leukocyte antigen-matched third-party in vitro expanded EBV-specific cytotoxic T lymphocytes (CTLs) to treat 2 CBT recipients with life-threatening, donor-derived monoclonal EBV(+) diffuse large B-cell lymphomas with extranodal involvement developing in the context of graft-versus-host disease. Both patients had failed immunosuppression taper and Rituximab. After 5 and 9 infusions of 106 EBV-CTL/kg, respectively, each patient achieved a sustained complete remission without toxicity or graft-versus-host disease. Each is alive without recurrence at 20 and 15 months, respectively, post-EBV-PTLD diagnosis. This approach demonstrates the efficacy of using "off-the-shelf," virus-specific third-party CTLs restricted by human leukocyte antigens expressed by the tumor to treat otherwise lethal EBV-PTLD. Such therapy may also be applicable to the treatment of other infections and residual or recurrent malignancy after CBT. (Blood. 2010;116(23):5045-5049)