Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida.
Department of Medicine, Jackson Memorial Hospital, Miami, Florida.
Biol Blood Marrow Transplant. 2018 Apr;24(4):806-814. doi: 10.1016/j.bbmt.2017.11.038. Epub 2017 Dec 5.
The optimal viral load threshold at which to initiate preemptive cytomegalovirus (CMV) therapy in hematopoietic cell transplantation (HCT) recipients remains to be defined. In an effort to address this question, we conducted a retrospective study of 174 allogeneic HCT recipients who underwent transplantation at a single center between August 2012 and April 2016. During this period, preemptive therapy was initiated at the discretion of the treating clinician. A total of 109 patients (63%) developed CMV viremia. The median time to reactivation was 17 days (interquartile range, IQR, 7-30 days) post-HCT. A peak viremia ≥150 IU/mL was strongly associated with a reduced probability of spontaneous clearance (relative risk, .16; 95% confidence interval, .1-.27), independent of established clinical risk factors, including CMV donor serostatus, exposure to antithymocyte globulin, and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV <350 IU/mL (19 days; IQR, 11-35 days) compared with those who started antiviral therapy at higher viremia thresholds (33 days; IQR, 21-42 days; P = .02). The occurrence of treatment-associated cytopenias was frequent but similar in patients who started preemptive therapy at CMV <350 IU/mL and those who started at CMV >350 IU/mL (44% versus 57%; P = .42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32% versus 0%; P = .001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74% reduction in 1-year nonrelapse mortality (NRM) (adjusted hazard ratio [HR], .26; 95% confidence interval [CI], .1-.8; P = .02), whereas therapeutic failure was associated with a significant increase in the probability of 1-year NRM (adjusted HR, 26; 95% CI, 8-87; P <.0001). We conclude that among allogeneic HCT patients, a peak CMV viremia ≥150 IU/mL is associated with a >80% reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for preemptive therapy. Delaying initiation of therapy until a CMV value ≥350 IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM.
启动 preemptive 治疗的最佳病毒载量阈值仍有待确定。为了解决这个问题，我们对 2012 年 8 月至 2016 年 4 月期间在一家中心接受同种异体造血细胞移植（HCT）的 174 名患者进行了回顾性研究。在此期间，根据治疗医生的判断启动 preemptive 治疗。共有 109 名患者（63%）发生 CMV 病毒血症。移植后 17 天（中位数，IQR，7-30 天）出现病毒血症再激活。病毒载量峰值≥150IU/mL 与自发清除率降低的概率显著相关（相对风险，.16；95%置信区间，.1-27），与包括 CMV 供体血清学状态、使用抗胸腺细胞球蛋白和潜在的淋巴恶性肿瘤在内的既定临床危险因素无关。与那些在 CMV<350IU/mL 时开始治疗的患者相比（19 天；IQR，11-35 天），那些在更高的病毒血症阈值时开始抗病毒治疗的患者（33 天；IQR，21-42 天；P=0.02）清除病毒血症的时间明显缩短。在 CMV<350IU/mL 时开始预防性治疗的患者和在 CMV>350IU/mL 时开始治疗的患者中，治疗相关血细胞减少症的发生率均较高且相似（44%对 57%；P=0.42）。治疗第 35 天未解决的 CMV 病毒血症与治疗失败风险增加相关（32%对 0%；P=0.001）。治疗第 35 天消除 CMV 病毒血症与 1 年非复发死亡率（NRM）降低 74%相关（校正后的危险比[HR]，.26；95%置信区间[CI]，.1-.8；P=0.02），而治疗失败与 1 年 NRM 概率显著增加相关（校正 HR，26；95% CI，8-87；P<.0001）。我们得出结论，在异基因 HCT 患者中，CMV 病毒血症峰值≥150IU/mL 与自发清除率降低的概率相关，其独立于 ATG 给药、CMV 供体血清学状态和淋巴恶性肿瘤，且是预防性治疗的合理阈值。延迟到 CMV 值≥350IU/mL 时才开始治疗会导致 CMV 病毒血症持续时间延长，而治疗第 35 天未解决的病毒血症与 NRM 显著增加相关。
