Spivey John F, Singleton Dana, Sweet Stuart, Storch Gregory A, Hayashi Robert J, Huddleston Charles B, Danziger-Isakov Lara A
Division of Allergy/Pulmonary, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
Pediatr Transplant. 2007 May;11(3):312-8. doi: 10.1111/j.1399-3046.2006.00626.x.
CMV infection causes morbidity and mortality after transplantation. Despite a wide range of prevention strategies among pediatric lung transplant programs, the optimal duration of prophylactic therapy against CMV infection in pediatric lung transplantation is unknown. To assess the feasibility, safety, and short-term efficacy of extending intravenous ganciclovir administration from six wk duration to 12 wk duration in pediatric lung transplant recipients. An open-label pilot study was performed in primary pediatric lung transplant recipients with donor and/or recipient CMV seropositivity. Intravenous ganciclovir was given for 12 wk post-transplantation. Subjects were tracked for protocol completion. Toxicities monitored included renal dysfunction, myelosuppression, gastrointestinal and neurological complications, as well as infection related to indwelling catheter placement. Serial CMV levels were measured to determine short-term efficacy of the intervention. Nine of nine subjects enrolled completed the pilot study. Subjects' ages ranged from six to 18 yr. Indications for lung transplantation included cystic fibrosis (n = 7), idiopathic pulmonary hypertension (n = 1), and complex congenital heart disease with pulmonary hypertension (n = 1). Seven subjects underwent deceased donor bilateral lung transplantation and two subjects underwent heart-lung transplantation. No subjects had protocol-defined drug toxicity. No episodes of neutropenia, thrombocytopenia, or renal toxicity occurred. Five subjects had catheter-related infections (three after week 12 of ganciclovir). Seven of nine subjects had CMV detected by PCR (four prior to ganciclovir completion) with only one subject having a positive viral culture for CMV viremia (prior to ganciclovir completion). No subjects had UL-97 mutation for ganciclovir resistance detected. The use of prolonged prophylactic administration of ganciclovir for 12 wk duration is a feasible, safe, and effective treatment to prevent CMV viremia based on viral culture in at risk pediatric lung transplant recipients. Further clinical studies are underway to determine optimal CMV prevention strategies.
巨细胞病毒（CMV）感染会导致移植后发病和死亡。尽管小儿肺移植项目中有多种预防策略，但小儿肺移植中预防CMV感染的最佳治疗持续时间尚不清楚。为了评估在小儿肺移植受者中将静脉注射更昔洛韦的给药时间从6周延长至12周的可行性、安全性和短期疗效。对供体和/或受体CMV血清学阳性的原发性小儿肺移植受者进行了一项开放标签的试点研究。移植后给予静脉注射更昔洛韦12周。追踪受试者以完成方案。监测的毒性包括肾功能障碍、骨髓抑制、胃肠道和神经系统并发症，以及与留置导管放置相关的感染。测量系列CMV水平以确定干预的短期疗效。入组的9名受试者全部完成了试点研究。受试者年龄在6至18岁之间。肺移植的指征包括囊性纤维化（n = 7）、特发性肺动脉高压（n = 1）和伴有肺动脉高压的复杂先天性心脏病（n = 1）。7名受试者接受了脑死亡供体双侧肺移植，2名受试者接受了心肺移植。没有受试者出现方案定义的药物毒性。未发生中性粒细胞减少、血小板减少或肾毒性事件。5名受试者发生了与导管相关的感染（3例在更昔洛韦治疗12周后）。9名受试者中有7名通过PCR检测到CMV（4例在更昔洛韦治疗完成前），只有1名受试者CMV病毒血症的病毒培养呈阳性（在更昔洛韦治疗完成前）。未检测到任何受试者存在更昔洛韦耐药的UL - 97突变。基于病毒培养，在有风险的小儿肺移植受者中，延长更昔洛韦预防性给药12周是预防CMV病毒血症的一种可行、安全且有效的治疗方法。进一步的临床研究正在进行中，以确定最佳的CMV预防策略。
