Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
J Heart Lung Transplant. 2010 Sep;29(9):1014-20. doi: 10.1016/j.healun.2010.04.022. Epub 2010 Jul 3.
Valganciclovir prophylaxis is advocated for lung transplant recipients, but its efficacy is unknown.
Retrospective review was done of 109 donor-positive/recipient-negative lung transplant patients who received alemtuzumab induction and valganciclovir for cytomegalovirus prophylaxis.
Median duration of follow-up after transplant was 27 months. Valganciclovir dose reductions (< 900 mg/day or renal-equivalent) were required for 18 patients (17%) due to toxicity, most commonly for neutropenia (n = 15) or gastrointestinal symptoms (n = 2). Of the 109 patients, 34 (31%) had no CMV infections, 45 (41%) had asymptomatic viremia, and 30 (27%) had CMV disease. CMV disease developed off prophylaxis in 10 patients (18%) at a median of 8.7 months after transplant and 2 months after valganciclovir discontinuation. Breakthrough disease occurred during prophylaxis in 10 patients (9%) at a median of 6.7 months. Patients with asymptomatic viremia or no CMV infection received prophylaxis for median 8.6 and 8.7 months, respectively. Risk factors for CMV disease by univariate analysis were increased age (p = 0.01), single-lung transplant (p = 0.03), chronic obstructive pulmonary disease (p = 0.05), reduced-dose valganciclovir (p = 0.001), and less than 6 months of prophylaxis (p = 0.005). By multivariate analysis, advanced age (p = 0.01) and reduced-dose valganciclovir (p = 0.0006) were independent risk factors for CMV disease. CMV disease developed in 4 patients (4%) due to ganciclovir-resistant viruses. CMV-attributable mortality was 5% (5 of 109), including 100% (4 of 4) with ganciclovir-resistant disease.
Valganciclovir prophylaxis among donor-positive/recipient-negative lung transplant recipients delayed but did not eliminate CMV disease or CMV-related deaths and was limited by toxicity and ganciclovir-resistance. Our experience suggests that valganciclovir at reduced-doses or for less than 6 months is sub-optimal in preventing CMV disease.
虽然环丙沙星预防方案被推荐用于肺移植受者，但该方案的疗效尚不清楚。
对 109 例接受阿仑单抗诱导和更昔洛韦预防巨细胞病毒的供体阳性/受体阴性肺移植患者进行了回顾性研究。
移植后中位随访时间为 27 个月。由于毒性作用，18 例（17%）患者需要减少环丙沙星剂量（<900mg/天或等效肾剂量），最常见的原因是中性粒细胞减少（n=15）或胃肠道症状（n=2）。在 109 例患者中，34 例（31%）无 CMV 感染，45 例（41%）无症状病毒血症，30 例（27%）CMV 疾病。10 例（18%）患者在移植后 8.7 个月和环丙沙星停药后 2 个月时出现 CMV 疾病，该疾病在预防期之外发生。10 例（9%）患者在预防期间发生突破性疾病，中位时间为 6.7 个月。无症状病毒血症或无 CMV 感染的患者分别接受了中位 8.6 个月和 8.7 个月的预防治疗。单因素分析显示，CMV 疾病的危险因素为年龄较大（p=0.01）、单肺移植（p=0.03）、慢性阻塞性肺疾病（p=0.05）、减少剂量的环丙沙星（p=0.001）和预防治疗时间<6 个月（p=0.005）。多因素分析显示，年龄较大（p=0.01）和减少剂量的环丙沙星（p=0.0006）是 CMV 疾病的独立危险因素。由于耐更昔洛韦病毒，4 例（4%）患者发生 CMV 疾病。CMV 相关死亡率为 5%（109 例中有 5 例），包括 4 例（4 例）耐更昔洛韦病毒的患者。
供体阳性/受体阴性肺移植受者的环丙沙星预防方案虽然延迟了，但并未消除 CMV 疾病或 CMV 相关死亡，且受到毒性和耐更昔洛韦病毒的限制。我们的经验表明，减少剂量或预防治疗时间<6 个月的环丙沙星预防方案并不理想，无法预防 CMV 疾病。
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