National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Office of Patient Safety and Clinical Quality, Clinical Center, National Institutes of Health, Bethesda, Maryland.
Biol Blood Marrow Transplant. 2019 Mar;25(3):577-586. doi: 10.1016/j.bbmt.2018.10.011. Epub 2018 Oct 18.
Human cytomegalovirus (CMV) infection and disease remains a significant cause of morbidity and mortality for hematopoietic cell transplantation (HCT) recipients. Disruption of or weak reconstitution of virus-specific cellular immune function, such as with certain HCT approaches, poses significant risk for CMV-related complications. The incidence of and risk factors for CMV infection and the nature of CMV disease were evaluated retrospectively among 356 consecutive HCT recipients transplanted at the National Institutes of Health using all graft sources, including bone marrow, peripheral blood stem cell (PBSC), and umbilical cord blood (UCB), and a range of in vivo and ex vivo approaches for graft-versus-host disease (GVHD) prophylaxis. The cumulative incidence of CMV infection was higher for CMV-seropositive recipients at 33%, regardless of donor CMV serostatus. Patients transplanted with CMV-seropositive donors had a significantly shorter duration of antiviral therapy. Among graft sources UCB was associated with the highest cumulative incidence of CMV infection at 65% and significantly longer treatment duration at a median of 36days, whereas PBSC HCT was associated with the lowest incidence at 26% and the shortest CMV treatment duration at a median of 21days. There were significant differences in the cumulative incidence of CMV infection by T cell manipulation strategy when systemic steroids were included as a risk-modifying event. Over one-third of CMV infections occurred in the setting of systemic steroid administration. CMV disease occurred in 5% of HCT recipients, with 70% of cases in the setting of treatment for GVHD. Although factors related to serostatus, graft source, and GVHD prophylaxis were associated with varied CMV infection incidence, unplanned post-HCT corticosteroid therapy contributed greatly to the incidence of both CMV infection and disease across HCT approaches, highlighting this post-HCT intervention as a key time to potentially tailor the approach to monitoring, preemptive therapy, and even prophylaxis.
人巨细胞病毒(CMV)感染和疾病仍然是造血细胞移植(HCT)受者发病和死亡的重要原因。某些 HCT 方法会破坏或削弱病毒特异性细胞免疫功能,从而使 CMV 相关并发症的风险显著增加。本研究回顾性评估了在国立卫生研究院(NIH)接受所有移植物来源(包括骨髓、外周血干细胞[PBSC]和脐带血[UCB])以及一系列体内和体外方法预防移植物抗宿主病(GVHD)的 356 例连续 HCT 受者中 CMV 感染和疾病的发生率和危险因素。CMV 感染的累积发生率在 CMV 血清阳性受者中较高,为 33%,而与供者 CMV 血清状态无关。与 CMV 血清阳性供者移植的患者抗病毒治疗时间明显缩短。在移植物来源中,UCB 与最高的 CMV 感染累积发生率(65%)相关,且中位治疗时间显著延长(36 天),而 PBSC HCT 与最低的发生率(26%)和最短的 CMV 治疗时间(中位 21 天)相关。在包括全身类固醇作为风险修饰事件的情况下,T 细胞操作策略的累积 CMV 感染发生率存在显著差异。超过三分之一的 CMV 感染发生在全身类固醇给药的情况下。HCT 受者中有 5%发生 CMV 疾病,其中 70%的病例发生在 GVHD 治疗的情况下。虽然与血清状态、移植物来源和 GVHD 预防相关的因素与 CMV 感染发生率的变化有关,但计划外的 HCT 后皮质类固醇治疗对各种 HCT 方法的 CMV 感染和疾病的发生率都有很大影响,这突出了该 HCT 后干预措施作为一个潜在的关键时间点,以调整监测、预防性治疗甚至预防策略。