Objective: To evaluate and compare the efficacies of ganciclovir plus foscarnet and a single agent for the treatment of cytomegalovirus (CMV) infection after haploidentical hematopoietic stem cell transplantation. Methods: This study was a non-randomized clinical controlled trial. The data of patients who underwent haploidentical transplantation and developed CMV infection between January 1, 2021, and June 30, 2021, were retrospectively analyzed. Follow-up was conducted through telephone, inpatient consultations, and the review of outpatient medical records. The observed indicators included the incidence of CMV infection (including CMV disease), rate of recurrence of CMV infection, overall survival (OS), and disease-free survival (DFS). Results: A total of 242 patients were diagnosed with post-transplantation CMV infection; 116 patients tested positive for CMV DNA for more than 14 days (P=0.011). Of the 242 patients with CMV infection, 65 were treated with ganciclovir plus foscarnet, and 156 patients were treated with a single antiviral drug; the median durations of CMV seroconversion were 21 (3-60) and 14 (3-32) days for the combination and single-drug groups, respectively. There were no significant differences between their incidence of CMV infections and 1-year OS and DFS. Of the patients with refractory CMV infections, 53 (45.7%) were treated with ganciclovir plus foscarnet, and 63 (54.3%) were treated with a single antiviral agent. The median durations of CMV seroconversion for the combination and single-drug groups were 21 (15-60) days and 20 (15-45) days, respectively (P=0.472). Two patients in each group progressed to CMV disease (P=0.860). During follow-up, 12 patients (22.6%) in the combination group and 8 patients (12.7%) in the single-drug group experienced recurrent episode(s) of CMV infection (P=0.158). The 1-year OS of the combination and single-drug groups were 92.0% and 87.1%, respectively (P=0.543); the 1-year DFS were 90.3% and 85.7%, respectively (P=0.665). Univariate analysis revealed no associations between the antiviral agents used and OS and DFS (OS: HR=0.644, P=0.547; DFS: HR=0.757, P=0.666). Conclusions: There were no significant differences in the duration of CMV infection, incidence of CMV disease, rate of recurrence of CMV infection, and survival of the patients treated with the combination of antiviral drugs and a single antiviral drug.
目的： 评估在单倍型造血干细胞移植后发生巨细胞病毒（CMV）血症的患者中，采用更昔洛韦、膦甲酸钠两种药物进行联合治疗，或采用其中一种药物进行单药治疗的疗效。 方法： 非随机对照研究。回顾性分析2021年1月1日至2021年6月30日北京大学人民医院接受单倍型造血干细胞移植、并在移植后发生CMV血症的患者。通过电话或查阅住院及门诊病历的方式进行随访。观测指标包括： CMV感染（包括CMV病）的发生率、CMV感染再发率、总体生存（OS）和无疾病生存（DFS）等。生存率采用Kaplan-Meier法分析，并进行log-rank检验。 结果： 共纳入血浆CMV DNA阳性的患者242例，其中221例接受抗病毒药物治疗，65例接受联合治疗，156例接受单药治疗。两组CMV血症转阴中位时间分别为21（3~60）及14（3~32） d（P=0.011）。两组在CMV病发生率、预计1年总体生存及无复发生存等方面差异均无统计学意义。CMV DNA阳性持续超过14 d（即难治性CMV感染）的患者共116例，53例（45.7%）在CMV阳性2周内接受了联合抗病毒治疗，63例（54.3%）则接受了单药抗病毒治疗。联合组和单药组中CMV DNA转阴的中位时间分别为21（15~60）及20（15~45） d（P=0.472）。两组中各有2例患者进展为CMV病（P=0.860）。在随访中，联合用药组有12例患者（22.6%）再次出现CMV血症；单药治疗组中，8例患者（12.7%）再次出现CMV血症（P=0.158）。联合用药组及单药治疗组预计1年OS率分别为92.0%及87.1%（P=0.543）；预计1年DFS分别为90.3%及85.7%（P=0.665）。单因素分析提示，OS、DFS与是否联合用药无相关性（OS：HR=0.644，P=0.547；DFS：HR=0.757，P=0.666）。 结论： 在难治性CMV感染中，联合应用抗病毒药物对比单药治疗，在CMV血症持续时间、CMV病发生率及CMV再发率、总体生存及无病生存等方面差异无统计学意义。.