Objective: To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival.
Methods: A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed.
Results: For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×104 copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×109/L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×104 copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005).
Conclusion: The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×104 copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.
题目: 异基因造血干细胞移植术后巨细胞病毒感染的临床研究.
目的: 探讨异基因造血干细胞移植后巨细胞病毒（CMV）和难治性CMV感染（RCI）发生的危险因素及对生存的影响。.
方法: 回顾性分析2015-2020年在重庆医科大学附属第一医院行异基因造血干细胞移植的246例患者的临床资料，根据是否感染CMV将患者分为CMV组（67例）和non-CMV组（179例），再根据是否发生RCI将CMV患者进一步分为RCI组（18例）和non-RCI组（49例）。分析CMV感染和RCI的危险因素，并用ROC曲线验证Logistic回归模型的诊断意义，同时分析组间的总生存期（OS）和无进展生存期差异，以及影响OS的危险因素。.
结果: 发生CMV感染的患者，首次CMV感染的中位时间为移植后48（7-183）d，感染持续的中位时间为21（7-158）d。患者年龄偏大、合并EB病毒（EBV）血症或者发生Ⅱ-Ⅳ度急性移植物抗宿主病均能显著增加CMV感染风险（P=0.032，<0.001和0.037），RCI的危险因素为EBV血症和诊断时的CMV-DNA峰值≥1×104 copies/ml（P=0.039，0.006），而移植后14 d的白细胞≥4×109/L是CMV感染和RCI的保护因素（P=0.013，0.014）。CMV组的OS率显著低于non-CMV组（P=0.033），RCI组的OS率亦显著低于non-RCI组（P=0.043）。造血重建是OS的有利因素（P<0.001），而移植后60 d内CMV-DNA≥1.0×104 copies/ml是OS的危险因素（P=0.005）。.
结论: 移植后白细胞数量恢复较晚以及合并EBV血症是CMV感染和RCI的共同危险因素；CMV-DNA载量1×104 copies/ml是重要临界值，高于该值可导致高RCI及低OS风险。.
Keywords: allogeneic hematopoietic stem cell transplantation; cytomegalovirus infection; refractory; risk factor.