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Prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplants.
Clinical Microbiology Reviews ( IF 36.8 ) Pub Date : 2003-10-15 , DOI: 10.1128/cmr.16.4.647-657.2003
Ellen Meijer 1 , Greet J Boland , Leo F Verdonck
Affiliation  

The main risk factors for cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants (SCT) are recipient CMV seropositivity and acute graft-versus-host disease. Currently, two antiviral strategies, prophylactic or preemptive antiviral treatment, are used for prevention of CMV disease. Preemptive treatment is most favorable when short-term (14-day) treatment is applied. Several methods are available for monitoring of CMV reactivation. PCR-based CMV DNA detection assays are the most sensitive methods; however, the clinical benefit of this high sensitivity is unclear. Even more, there is lack of clarity whether PCR tests can better be performed with plasma, whole blood, or peripheral blood leukocyte samples. Recovery of a CMV-specific CD8(+) cytotoxic-T-lymphocyte (CTL) response is necessary for preventing CMV reactivation and disease. Reconstitution of absolute CMV-specific CTL counts to values above 10 x 10(6) to 20 x 10(6) CTLs/liter is associated with protection from CMV disease. In the near future, preemptive therapy might be withheld in patients with CMV reactivation who are shown to have adequate CMV-specific cytotoxic T-cell levels. Antiviral therapy with (val)acyclovir has been studied only as prophylactic treatment for prevention of CMV infection. High-dose oral valacyclovir is more effective than acyclovir when used in addition to preemptive treatment of CMV reactivation with ganciclovir or foscarnet. Three antiviral drugs have been tested for preemptive therapy of CMV reactivation and/or treatment of CMV disease. Although intravenous ganciclovir is considered the drug of choice, foscarnet has similar efficacy and less toxicity, especially hematologic toxicity. Cidofovir has not been tested extensively, but so far the results are disappointing. Oral valganciclovir for preemptive treatment of SCT recipients is currently being studied. In addition to antiviral therapy, adoptive immunotherapy with CMV-specific cytotoxic T cells as prophylactic or preemptive therapy is a very elegant strategy; however, generation of these cells is expensive and time-consuming, and therefore the therapy is not available at every transplantation center. Magnetic selection of CMV-specific CD8(+) T cells from peripheral blood by using HLA class I-peptide tetramers may be very promising, making this strategy more accessible.

中文翻译:

异基因干细胞移植受者中巨细胞病毒疾病的预防。

同种异体干细胞移植(SCT)接受者中巨细胞病毒(CMV)疾病的主要危险因素是接受者CMV血清反应阳性和急性移植物抗宿主病。当前,预防性或先发性抗病毒治疗的两种抗病毒策略被用于预防CMV疾病。当应用短期(14天)治疗时,抢先治疗是最有利的。有几种方法可用于监视CMV重新激活。基于PCR的CMV DNA检测方法是最灵敏的方法。但是,这种高敏感性的临床益处尚不清楚。甚至还不清楚是否可以用血浆,全血或外周血白细胞样本更好地进行PCR测试。恢复CMV特异性CD8(+)细胞毒性T淋巴细胞(CTL)反应对于预防CMV激活和疾病是必需的。将特定于CMV的绝对CTL计数重构为高于10 x 10(6)至20 x 10(6)CTL /升的值与保护CMV疾病无关。在不久的将来,对于具有巨细胞病毒特异性细胞毒性T细胞水平的巨细胞病毒再激活患者,可能会放弃先发疗法。(val)acyclovir的抗病毒治疗仅作为预防CMV感染的预防方法进行了研究。当使用更昔洛韦或膦甲膦酸抢先治疗CMV活化时,大剂量口服伐昔洛韦比阿昔洛韦更有效。已经测试了三种抗病毒药物用于CMV活化的先发治疗和/或CMV疾病的治疗。尽管静脉注射更昔洛韦被认为是首选药物,但膦甲酸具有相似的功效且毒性较小,尤其是血液学毒性。西多福韦尚未经过广泛测试,但到目前为止结果令人失望。目前正在研究口服缬更昔洛韦用于SCT受体的抢先治疗。除抗病毒治疗外,采用CMV特异性细胞毒性T细胞作为预防性或抢先性疗法的过继免疫疗法是一种非常出色的策略。然而,这些细胞的产生是昂贵且费时的,因此并非在每个移植中心都可获得该疗法。通过使用HLA I类肽四聚体从外周血中磁选择CMV特异性CD8(+)T细胞可能是非常有前途的,使这种策略更容易获得。膦甲酸具有相似的功效,毒性较小,尤其是血液学毒性。西多福韦尚未经过广泛测试,但到目前为止结果令人失望。目前正在研究口服缬更昔洛韦用于SCT受体的抢先治疗。除抗病毒治疗外,采用CMV特异性细胞毒性T细胞作为预防性或抢先性疗法的过继免疫疗法是一种非常出色的策略。然而,这些细胞的产生是昂贵且费时的,因此并非在每个移植中心都可获得该疗法。通过使用HLA I类肽四聚体从外周血中磁选择CMV特异性CD8(+)T细胞可能是非常有前途的,使这种策略更容易获得。膦甲酸具有相似的功效,毒性较小,尤其是血液学毒性。西多福韦尚未经过广泛测试,但到目前为止结果令人失望。目前正在研究口服缬更昔洛韦用于SCT受体的抢先治疗。除抗病毒治疗外,采用CMV特异性细胞毒性T细胞作为预防性或抢先性疗法的过继免疫疗法是一种非常出色的策略。然而,这些细胞的产生是昂贵且费时的,因此并非在每个移植中心都可获得该疗法。通过使用HLA I类肽四聚体从外周血中磁选择CMV特异性CD8(+)T细胞可能是非常有前途的,使这种策略更容易获得。但到目前为止,结果令人失望。目前正在研究口服缬更昔洛韦用于SCT受体的抢先治疗。除抗病毒治疗外,采用CMV特异性细胞毒性T细胞作为预防性或抢先性疗法的过继免疫疗法是一种非常出色的策略。然而,这些细胞的产生是昂贵且费时的,因此并非在每个移植中心都可获得该疗法。通过使用HLA I类肽四聚体从外周血中磁选择CMV特异性CD8(+)T细胞可能是非常有前途的,使这种策略更容易获得。但到目前为止,结果令人失望。目前正在研究口服缬更昔洛韦用于SCT受体的抢先治疗。除抗病毒治疗外,采用CMV特异性细胞毒性T细胞作为预防性或抢先性疗法的过继免疫疗法是一种非常出色的策略。然而,这些细胞的产生是昂贵且费时的,因此并非在每个移植中心都可获得该疗法。通过使用HLA I类肽四聚体从外周血中磁选择CMV特异性CD8(+)T细胞可能是非常有前途的,使这种策略更容易获得。以CMV特异性细胞毒性T细胞作为预防性或抢先性疗法的过继免疫疗法是一种非常巧妙的策略;然而,这些细胞的产生是昂贵且费时的,因此并非在每个移植中心都可获得该疗法。通过使用HLA I类肽四聚体从外周血中磁选择CMV特异性CD8(+)T细胞可能是非常有前途的,使这种策略更容易获得。以CMV特异性细胞毒性T细胞作为预防性或抢先性疗法的过继免疫疗法是一种非常巧妙的策略;然而,这些细胞的产生是昂贵且费时的,因此并非在每个移植中心都可获得该疗法。通过使用HLA I类肽四聚体从外周血中磁选择CMV特异性CD8(+)T细胞可能是非常有前途的,使这种策略更容易获得。
更新日期:2019-11-01
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