Complete regression of posttransplant lymphoproliferative disease using partially HLA-matched Epstein Barr virus-specific cytotoxic T cells
Complete regression of posttransplant lymphoproliferative disease using partially HLA-matched Epstein Barr virus-specific cytotoxic T cells
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DOI：
10.1097/00007890-200110270-00012
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发表时间：
2001-10-27
期刊：
影响因子：
6.2
通讯作者：
Crawford, DH
中科院分区：
文献类型：
--
作者：
Haque, T;Taylor, C;Crawford, DH
背景。自体和供体来源的细胞毒性T淋巴细胞（CTL）的过继免疫疗法最近被用于治疗eb病毒（EBV）阳性的移植后淋巴细胞增生性疾病（PTLD）。方法与结果。我们报道了一名18个月大的小肠和肝脏移植受体在输注部分人白细胞抗原（HLA）匹配的EBV特异性CTL后，EBV阳性PTLD完全消退。CTL来自EBV血清阳性的无血缘关系的献血者。没有观察到输注相关的毒性或移植物抗宿主病的证据。肿瘤在1周内出现消退迹象，外周血EBV载量降至检测不到的水平。限制性稀释分析（LDA）在输注前未检测到ebv特异性CTL前体（CTLp）细胞，而在CTL输注后4小时和24小时检测到大量CTLp细胞。外周血中CD4/8比例逆转，HLA-DR阳性CD8细胞增加。患者已完全缓解24个月。如果在更多的PTLD患者中重复这一成功，那么储存的CTL可以用于免疫功能低下患者的抗病毒和抗肿瘤治疗。
Background. Adoptive immunotherapy with autologous and donor-derived cytotoxic T lymphocytes (CTL) has recently been used to treat Epstein Barr virus (EBV)-positive posttransplant lymphoproliferative disease (PTLD).Methods and results. We report complete regression of EBV-positive PTLD in an 18-month-old small bowel and liver transplant recipient after one infusion of partially human leukocyte antigen (HLA)-matched EBV-specific CTL grown ex vivo from an EBV seropositive unrelated blood donor. No infusion-related toxicity or evidence of graft-versus-host disease was observed. The tumor showed signs of regression within 1 week and EBV load in peripheral blood dropped to undetectable levels. Limiting dilution analyses (LDA) detected no EBV-specific CTL precursor (CTLp) cells before the infusion, and high numbers of CTLp at 4 hr and 24 hr post-CTL infusion. There was a reversal of the CD4/8 ratio in peripheral blood and an increase in HLA-DR positive CD8 cells. The patient has been in complete remission for 24 months.Conclusion. If this success is repeated in more PTLD patients, then stored CTL could be used for antiviral and antitumor therapies in immunocompromised patients.