Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients
Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients
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DOI：
10.1182/blood.v92.5.1549.417k32_1549_1555
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发表时间：
1998-09-01
期刊：
影响因子：
20.3
通讯作者：
Heslop, HE
中科院分区：
文献类型：
--
作者：
Rooney, CM;Smith, CA;Heslop, HE
EB病毒（EBV）导致高达25%的接受无关或HLA不匹配供体骨髓移植的儿童发生潜在致命的免疫母细胞淋巴瘤。由于这种并发症似乎源于EBV特异性细胞毒性T细胞的缺乏，我们评估了供体来源的多克隆（CD 4（+）和CD 8（+））T细胞系作为EBV相关淋巴瘤的免疫预防和治疗的安全性和有效性。39名被认为是EBV诱导的淋巴瘤高风险的患者在接受来自HLA匹配的无关供体（n = 33）或不匹配的家庭成员（n = 6）的T细胞耗尽的骨髓后，各自接受2至4次来自供体的EBV特异性T淋巴细胞的静脉输注。在输注期间和输注后监测该疗法的免疫学效果。通过检测neo标记基因鉴定输注的细胞。除1例患者外，在所有患者中均鉴定出携带neo标志物的EBV特异性T细胞。DNA的系列分析在未经处理的外周血单核细胞中检测标记基因长达18周，在EBV特异性细胞毒性T细胞的再生系中检测标记基因长达38个月。6名患者（15.5%）在研究开始时EBV-DNA的量大大增加（> 2，000个基因组拷贝/10（6）个单核细胞），表明EBV复制不受控制，这是一种与随后明显淋巴瘤发展高度相关的并发症。所有这些患者在输注后2至3周内显示病毒DNA水平降低2至4个对数，并且没有发生淋巴瘤，证实了供体来源的细胞的抗病毒活性。没有可归因于预防性T细胞治疗的毒性作用。另外两名未接受预防治疗并发生明显免疫母细胞淋巴瘤的患者对T细胞输注完全应答。因此，对EBV蛋白特异性的多克隆供体来源的T细胞系可以安全地用于预防同种异体骨髓移植后的EBV相关免疫母细胞淋巴瘤，并且还可以有效治疗已建立的疾病。(C)1998年，美国血液学会。
Epstein-Barr virus (EBV) causes potentially lethal immunoblastic lymphoma in up to 25% of children receiving bone marrow transplants from unrelated or HLA-mismatched donors. Because this complication appears to stem from a deficiency of EBV-specific cytotoxic T cells, we assessed the safety and efficacy of donor-derived polyclonal (CD4(+) and CD8(+)) T-cell lines as immunoprophylaxis and treatment for EBV-related lymphoma. Thirty-nine patients considered to be at high risk for EBV-induced lymphoma each received 2 to 4 intravenous infusions of donor-derived EBV-specific T lymphocytes, after they had received T-cell-depleted bone marrow from HLA-matched unrelated donors (n = 33) or mismatched family members (n = 6). The immunologic effects of this therapy were monitored during and after the infusions. Infused cells were identified by detection of the neo marker gene. EBV-specific T cells bearing the neo marker were identified in all but 1 of the patients. serial analysis of DNA detected the marker gene for as long as 18 weeks in unmanipulated peripheral blood mononuclear cells and for as long as 38 months in regenerated lines of EBV-specific cytotoxic T cells. Six patients (15.5%) had greatly increased amounts of EBV-DNA on study entry (> 2,000 genome copies/10(6) mononuclear cells), indicating uncontrolled EBV replication, a complication that has had a high correlation with subsequent development of overt lymphoma. All of these patients showed 2 to 4 log decreases in viral DNA levels within 2 to 3 weeks after infusion and none developed lymphoma, confirming the antiviral activity of the donor-derived cells. There were no toxic effects that could be attributed to prophylactic T-cell therapy. Two additional patients who did not receive prophylaxis and developed overt immunoblastic lymphoma responded fully to T-cell infusion. Polyclonal donor-derived T-ceIl lines specific for EBV proteins can thus be used safely to prevent EBV-related immunoblastic lymphoma after allogeneic marrow transplantation and may also be effective in the treatment of established disease. (C) 1998 by The American Society of Hematology.