A PHASE III MULTICENTER STUDY OF VALGANCICLOVIR

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定是研究者机构。本研究的目的是确定缬更昔洛韦是否能有效预防晚期巨细胞病毒感染。在目前有效的预防性或先发制人的更昔洛韦治疗的时代，巨细胞病毒感染继续对异基因造血干细胞移植后的患者构成重大危害。在HSCT后CMV疾病的最高风险期，更昔洛韦导致CMV疾病的大幅减少。从历史上看，这些“早期CMV疾病”的病例被定义为移植后前100天内发生的病例。更昔洛韦在移植时给药或用于pp 65抗原血症或PCR检测CMV DNA时有效预防CMV疾病，并提高选定高危患者的生存率。晚期CMV疾病主要发生在移植后100天至365天之间。晚期CMV感染和疾病都是HSCT后死亡率的独立预测因素，即使晚期CMV感染和疾病风险最高的患者可以在第100天确定。这是因为几乎没有预防选择;更昔洛韦只能作为静脉注射制剂或作为吸收不良的口服药物。缬更昔洛韦是更昔洛韦的口服前体药物，吸收良好，产生的曲线下面积（AUC）与IV更昔洛韦相似，可以每天给药一次。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to determine whether valganciclovir is effective in the prevention of late CMV infection. In the current era of effective prophylactic or preemptive ganciclovir therapy, cytomegalovirus infections continue to pose a significant hazard for patients after alloegeneic hematopoietic stem cell transplantation. Ganciclovir has led to a major reduction of CMV disease during the period of highest risk for CMV disease after HSCT. Historically, these cases of "early CMV disease" were defined as those occurring during the first 100 days after transplantation. Ganciclovir effectively prevents CMV disease when given at engraftment or for pp65 antigenemia or detection of CMV DNA by PCR and improves survival in selected high-risk. Late CMV disease occurs primarily between day 100 and day 365 after transplant. Both late CMV infection and disease are independent predictors for mortality after HSCT, even though patients at highest risk for late CMV infection and disease can be identified by day 100. This is because few prophylactic options existed; ganciclovir was only available as intravenous formulation or as a poorly absorbed oral drug. Valganciclovir is an oral prodrug of ganciclovir that is well absorbed, produces an area under the curve (AUC) similar to that of IV ganciclovir and can be given once daily.