Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
Biol Blood Marrow Transplant. 2017 Oct;23(10):1759-1766. doi: 10.1016/j.bbmt.2017.06.008. Epub 2017 Jun 28.
Recipients of ex vivo T cell-depleted (TCD) hematopoietic cell transplantation (HCT) are at risk of infection by double-stranded (ds) DNA viruses. We report rates of dsDNA viremia, end-organ disease (EOD), infection-related mortality, and overall survival (OS) in a contemporary cohort of adult TCD HCT recipients routinely monitored for cytomegalovirus (CMV), adenovirus (ADV), human herpesvirus 6 (HHV6), and Epstein-Barr virus (EBV). Healthcare utilization in the first 6 months post-HCT was compared between patients with dsDNA viremia versus no viremia. This was an observational study of adult patients with acute leukemia and myelodysplastic syndrome who received CD34 selected, peripheral blood HCT at Memorial Sloan Kettering Cancer Center from March 2012 through December 2014. Patients were prospectively monitored by quantitative PCR assays for CMV, ADV, HHV6, and EBV in whole blood or plasma. The cumulative incidence of viremia(s) at day +180, EOD at 1 year, and OS at 1 year were estimated by the Kaplan-Meier method and compared by the log-rank test among patient with and without viremia/EOD. Standardized incidence ratios were used to compare overall length of hospital stay (LOS), number of readmissions after HCT, and length of readmissions through day +180. Of 156 patients, 96 (62%) were CMV recipient seropositive. Forty-two patients received grafts from matched related (27%), 86 from matched unrelated (55%), and 28 from mismatched (18%) donors. Overall, 132 patients (85%) had ≥1 viremia and 52 (33%) ≥2 viremias by day +180. The cumulative incidences for CMV, HHV6, ADV, and EBV viremia were 44%, 61%, 7%, and 16%, respectively, with median times of onset 28 days (interquartile range [IQR], 25 to 33), 33 days (IQR, 25 to 47), 60 days (IQR, 19 to 84), and 79 days (IQR, 54 to 106) post-HCT, respectively. Twenty-eight patients (18%) developed EOD by dsDNA viruses at 1 year post-HCT. Treatment for CMV accounted for 91% total antiviral treatment-days. Compared with patients with no viremia, patients with CMV viremia, HHV6 viremia, or ≥2 viremias experienced longer LOS (P <.001) and a higher number of readmissions (P <.001) by day +180. OS rate at 1 year was 79% and was similar between patients with or without dsDNA viremias. EOD was associated with lower 1-year OS rates (63.4%) versus without EOD (81.1%) (P = .02). Of 33 patients who died, 10 died due to infection, and 7 of these infection-related deaths were due to dsDNA viruses. Viremia by dsDNA viruses occurred in 85% of TCD HCT recipients by day +100 and 33% of patients experienced ≥2 viremias by day +180. CMV accounted for most antiviral use. CMV, HHV6, or ≥2 viremias were associated with more readmissions and longer LOS. One year OS rate was 78%. EOD by dsDNA viruses was associated with decreased 1-year OS. Infections by dsDNA viruses pose a substantial burden after TCD HCT.
受者在体外 T 细胞耗竭（TCD）造血细胞移植（HCT）后有感染双链 DNA 病毒（dsDNA 病毒）的风险。我们报告了在接受常规监测巨细胞病毒（CMV）、腺病毒（ADV）、人类疱疹病毒 6（HHV6）和 Epstein-Barr 病毒（EBV）的 TCD HCT 成年受者中，dsDNA 病毒血症、终末器官疾病（EOD）、感染相关死亡率和总生存率（OS）的发生率。在 HCT 后 6 个月内，比较了有 dsDNA 病毒血症与无病毒血症患者的医疗保健利用情况。这是一项对在 Memorial Sloan Kettering Cancer Center 接受 CD34 选择的外周血 HCT 的急性白血病和骨髓增生异常综合征成年患者进行的前瞻性观察研究。患者通过定量 PCR 检测法在全血或血浆中对 CMV、ADV、HHV6 和 EBV 进行监测。用 Kaplan-Meier 法估计第 180 天的病毒血症发生率（s）、1 年的 EOD 发生率和 1 年的 OS 发生率，并通过 log-rank 检验比较病毒血症/EOD 患者和无病毒血症/EOD 患者的差异。采用标准化发病率比比较总的住院时间（LOS）、HCT 后再入院的次数以及再入院至第 180 天的时间。在 156 例患者中，96 例（62%）为 CMV 受者血清阳性。42 例患者接受了匹配的亲缘供体（27%）、86 例接受了匹配的无关供体（55%）和 28 例接受了不匹配供体（18%）。总体而言，132 例患者（85%）在第 180 天有≥1 次病毒血症，52 例患者（33%）有≥2 次病毒血症。CMV、HHV6、ADV 和 EBV 病毒血症的累积发生率分别为 44%、61%、7%和 16%，发病中位时间分别为 28 天（四分位距[IQR]，25 至 33）、33 天（IQR，25 至 47）、60 天（IQR，19 至 84）和 79 天（IQR，54 至 106）。28 例患者（18%）在 HCT 后 1 年发生 EOD。CMV 的抗病毒治疗占总抗病毒治疗天数的 91%。与无病毒血症患者相比，CMV 病毒血症、HHV6 病毒血症或≥2 次病毒血症患者的 LOS 更长（P<.001），且在第 180 天前再入院的次数更多（P<.001）。1 年的 OS 率为 79%，且病毒血症患者与无病毒血症患者相似。EOD 与较低的 1 年 OS 率（63.4%）相关，而无 EOD 的 1 年 OS 率为 81.1%（P=.02）。在 33 例死亡患者中，有 10 例死于感染，其中 7 例与 dsDNA 病毒相关感染相关死亡（P=.02）。第 100 天，TCD HCT 受者中 85%有 dsDNA 病毒血症，第 180 天有 33%的患者有≥2 次病毒血症。CMV 导致了大多数抗病毒药物的使用。CMV、HHV6 或≥2 次病毒血症与更多的再入院和更长的 LOS 相关。1 年 OS 率为 78%。dsDNA 病毒引起的 EOD 与 1 年 OS 率降低相关。TCD HCT 后，dsDNA 病毒感染给患者带来了沉重的负担。
