Objective: Donor cytomegalovirus (CMV) serological negative status may have an adverse effect on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT), while there is inadequate data for Chinese people. This study is to explore the impact of donor CMV serological status on the outcome of CMV seropositive patients receiving allo-HSCT. Methods: Our study retrospectively analyzed 16 CMV seropositive patients with hematological malignancies receiving allogeneic grafts from CMV seronegative donors (antibody IgG negative) at Peking University People's Hospital from March 2013 to March 2020, which was defined as D-/R+ group. The other 64 CMV seropositive patients receiving grafts from CMV seropositive donors at the same period of time were selected as matched controls through a propensity score with 1∶4 depending on age, disease state and donor-recipient relationship (D+/R+ group). Results: Patients in D-/R+ group developed CMV DNAemia later than patients in the D+/R+ group (+37 days vs. +31 days after allo-HSCT, P=0.011), but the duration of CMV DNAemia in D-/R+ group was longer than that of D+/R+ group (99 days vs. 34 days, P=0.012). The rate of CMV reactivation 4 times or more in D-/R+ group was 4/16, significantly higher than that of D+/R+ group (4.7%, 3/64, P=0.01). The incidences of refractory CMV DNAemia (14/16 vs. 56.3%, P=0.021) and CMV disease (4/16 vs. 4.7%, P=0.01) in D-/R+ group were both higher than those in D+/R+ group. In addition, the application of CMV-CTL as the second-line antiviral treatment in D-/R+ group was more than that in D+/R+ group. Univariate analysis and multivariate analysis suggested that CMV serological negativity is an independent risk factor for refractory CMV DNAemia and the duration of CMV infection. The cumulative incidence of aGVHDⅡ-Ⅳ, cGVHD, 3-year probability of NRM, overall survival, and the cumulative incidence of relapse were all comparable in two groups. Conclusions: Although there is no significant effect on OS and NRM, the incidence of refractory CMV DNAemia, the frequency of virus reactivation, and the development of CMV disease in D-/R+ group are higher than those in controls. Therefore, CMV seropositive donors are preferred for CMV seropositive patients.
目的: 研究巨细胞病毒(CMV)血清学阴性供者对CMV血清学阳性患者移植预后的影响。 方法: 回顾性分析2013年3月至2020年3月在北京大学人民医院血液科接受CMV血清学阴性供者(CMV IgG阴性)移植物的16例行异基因造血干细胞移植的恶性血液肿瘤患者,定义为CMV血清学阴性供者组(D-/R+组)。从同一时间段的其他患者中选择(以年龄、患者疾病状态和供受者关系为因素,按1∶4进行倾向得分匹配)64例作为对照组,即CMV血清学阳性供者组(D+/R+组),比较分析两组的CMV感染相关情况、总生存期(OS)、非复发相关病死(NRM)率和累计复发率。 结果: D-/R+组患者移植后首次出现CMV血症的中位时间稍晚于D+/R+组(移植后+37 d比+31 d,P=0.011),但移植后D-/R+组患者外周血CMV DNA首次和最终转阴中位时间要长于D+/R+组(首次:29 d比18 d,P<0.01;最终:99 d比34 d,P=0.012)。D-/R+组移植后CMV激活次数≥4次的比例为4/16,明显高于D+/R+组(4.7%,3/64,P=0.01)。D-/R+组难治性CMV血症(14/16 比56.3%,P=0.021)和CMV病的发生率(4/16比4.7%,P=0.01)均高于D+/R+组。经过抗病毒治疗后D-/R+组外周血CMV DNA转阴时间明显晚于D+/R+组,且该组启动二线治疗[CMV特异性细胞毒性T细胞(CMV-CTL)治疗]的比例明显升高。单因素分析和多因素分析均提示CMV血清学阴性供者是难治性CMV血症和CMV感染时长的独立危险因素。两组急性移植物抗宿主病(aGVHD)Ⅱ~Ⅳ、慢性移植物抗宿主病(cGVHD)的累积发生率、3年NRM率、累积复发率、总生存期差异均无统计学意义。 结论: 尽管对OS、NRM率无明显影响,CMV血清学阴性供者组的难治性CMV血症发生率、CMV感染持续时长、病毒激活次数和CMV病发生率均明显高于CMV血清学阳性供者组。因此CMV血清学阳性患者应优先考虑CMV血清学阳性供者。.