A PHASE III MULTICENTER STUDY OF VALGANCICLOVIR

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的目的是确定缬更昔洛韦是否有效预防晚期巨细胞病毒感染。在当前更昔洛韦有效预防或先发制人治疗的时代，巨细胞病毒感染继续对异体造血干细胞移植后患者构成重大危害。更昔洛韦在造血干细胞移植后巨细胞病毒疾病风险最高的时期导致巨细胞病毒疾病的重大减少。历史上，这些“早期巨细胞病毒疾病”的病例被定义为在移植后的前100天内发生的病例。更昔洛韦在移植或pp65抗原血症或PCR检测CMV DNA时可有效预防CMV疾病，并提高选定高危患者的生存率。晚期巨细胞病毒疾病主要发生在移植后100天至365天之间。晚期巨细胞病毒感染和疾病都是HSCT后死亡率的独立预测因素，尽管晚期巨细胞病毒感染和疾病风险最高的患者可以在第100天确定。这是因为当时的预防措施很少；更昔洛韦仅作为静脉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药，吸收良好，产生与静脉更昔洛韦相似的曲线下面积（AUC），可每日服用一次。

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.