异基因造血干细胞移植后血巨细胞病毒定量监测及临床意义

Quantitative monitoring of blood cytomegalovirus after allogeneic hematopoietic stem cell transplantation and its clinical significance

目的 探讨异基因造血干细胞移植（allo-HSCT）后巨细胞病毒（CMV）的易感因素及CMV血症对allo-HSCT患者生存的影响。方法 Allo-HSCT患者从预处理开始至移植后3个月内，采用荧光定量PCR方法每周检测1次外周血单个核细胞CMV DNA拷贝数，应用单因素分析及多因素回归分析发生CMV血症的危险因素，比较并分析CMV血症与无CMV血症患者5年总生存率的差别。结果 183例患者中有132例（72.1%）发生CMV血症，其中78例（59.1%）发生在回输干细胞1个月后，54例（40.9%）发生在回输干细胞1个月内，回输干细胞后3个月内血中CMV检测持续阴性者51例（27.9%）。183例患者中只有2例明确诊断为CMV病，发生率为1.1%。单因素分析及多因素回归分析均显示，发生CMV血症的危险因素为移植方式和环孢素A（CsA）浓度＞300 μg/L。不同移植方式间两两比较显示亲缘相合移植与亲缘不全相合、无关供者及脐带血移植组之间CMV血症发生率差异均有统计学意义（P〈0.05），而亲缘不全相合、无关供者和脐带血移植组两两比较差异均无统计学意义，进一步将患者分为使用抗胸腺细胞球蛋白（ATG）组和未用ATG组进行统计分析，结果显示两组间CMV血症差异存在统计学意义（P〈0.001）。Kaplan-Meier生存曲线显示CMV血症与无CMV血症患者5年总生存率之间差异无统计学意义（P=0.387）。结论 Allo-HSCT后CMV血症发生率高达72.1%，使用ATG以及CsA浓度〉300 μg/L是发生CMV血症的主要危险因素。CMV血症对allo-HSCT患者的累计总生存率无显著影响，及时治疗CMV血症对防止CMV病有重要意义。

Objective To investigate the risk factor for cytomegalovirus （CMV） viremia and its impact on the survival of patients after allogeneic hematological stem cell transplantation （allo-HSCT）. Methods Quantitative fluorescence PCR was used to examine the quantity of CMV in mononuclear cells. All patients were tested weekly after allo-HSCT within 3 months. Univariate and multivariate analysis were used to determine the risk factors of CMV viremia. Five-year overall survival rate was compared and analyzed between the patients with or without CMV viremia. Results The incidence of CMV viremia was 72.1%（132/183）. Of which, 59.1%（78/132） occurred post one month after transplantation, 40.9%（54/132） occurred within one month and 27.9%（51/183） sustained negative within three months. Two cases were clearly diagnosed as CMV disease with a incidence of 1.1%. Both univariate and multivariate analysis indicated that transplant methods and blood cyclosporine A （CsA） concentration were significantly correlated with CMV viremia. When pairwise compared the results between the different transplant methods, significant differences of CMV viremia were found between human leukocyte antigen （HLA） matched sibling and HLA mismatched relatives, unrelatived donor or cord blood （all P values 〈0.05）. There was no significant difference between HLA mismatched relatives and unrelatived donor or cord blood. Further analysis showed that the incidence of CMV viremia was much higher in those who had used antithymocyte globulin （ATG） then those not used ATG. The Kaplan-Meier survival curve showed there was no significant difference between the groups with and without CMV viremia. Conclusions The incidence of CMV viremia after allo-HSCT is 72.1%. Administration of ATG during conditioning regimen and blood CsA concentration 〉300 μg/L are the main risk factors for CMV viremia. There is no significant effect of CMV viremia on the cumulative overall survival, while prompt treatment of CMV viremia is a crucial way to prevent CMV disease.