Epstein-Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease:: prophylactic infusion of EBV-specific cytotoxic T cells
Epstein-Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease:: prophylactic infusion of EBV-specific cytotoxic T cells
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DOI：
10.1182/blood.v95.3.807.003k24_807_814
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发表时间：
2000-02-01
期刊：
影响因子：
20.3
通讯作者：
Masucci, MG
中科院分区：
文献类型：
--
作者：
Gustafsson, Å;Levitsky, V;Masucci, MG
采用半定量聚合酶链反应检测9例异基因骨髓移植患者骨髓中EB病毒DNA水平。5例HLA不匹配的T细胞去除移植物的受者中有4例在BMT后1至3个月内表现出4至5个对数的EBV-DNA增加，从最大病毒负荷开始输注2至4次10（7）EBV特异性细胞毒性T淋巴细胞（CTL）/m2，导致3例患者病毒滴度下降2至3个对数。1例接受缺乏主要EBV特异性成分的T细胞培养的患者进展为致命性EBV阳性淋巴瘤。在EBV-DNA峰出现之前施用EBV-CTL导致第五名患者的病毒滴度稳定在高于正常水平2至3个对数内。在接受未经操作的HLA匹配移植物的4例患者中，也检测到病毒滴度的中度增加，而1例Wiskott-Aldrich综合征患者在BMT后70天内EBV-DNA载量达到5-log增加。我们的研究结果表明，循环EBV-DNA的快速增加发生在EBV特异性T细胞前体的情况下，或存在先天性免疫缺陷，阻止病毒特异性免疫的重建。BMT后早期预防性给予EBV-CTL似乎提供了最有效的保护，以防止EBV相关淋巴组织增生性疾病的发展。(C)2000年，美国血液学会。
A semiquantitative polymerase chain reaction assay was used to monitor the brood levels of Epstein-Barr virus (EBV)-DNA in 9 patients receiving allogeneic bone marrow transplants (BMT). Four of 5 recipients of HLA-mismatched T-cell-depleted grafts showed a 4- to 5-log increase of EBV-DNA within 1 to 3 months after BMT, Administration of 2 to 4 infusions of 10(7) EBV-specific cytotoxic T-lymphocytes (CTLs)/m(2) starting from the time of maximal virus load resulted in a 2- to 3-log decrease of virus titers in 3 patients. One patient, who received a T-cell culture lacking a major EBV-specific component, progressed to fatal EBV-positive lymphoma. Administration of EBV-CTLs before the onset of the EBV-DNA peak resulted in stabilization of the virus titers within 2 to 3 logs above the normal levels in the fifth patient. A moderate increase of virus titers was also detected in 3 of 4 patients receiving unmanipulated HLA-matched grafts, whereas 1 patient with Wiskott-Aldrich syndrome reached a 5-log increase of EBV-DNA load within 70 days after BMT. Our results suggest that a rapid increase of circulating EBV-DNA occurs in the absence of EBV-specific T-cell precursors or in the presence of congenital immune defects that prevent the reestablishment of virus-specific immunity. Prophylactic administration of EBV-CTLs early after BMT appears to provide the most effective protection against the development of EBV-associated lymphoproliferative disease.(C) 2000 by The American Society of Hematology.