Fred Hutchinson Cancer Center, Seattle, WA.
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA.
Blood Adv. 2023 Apr 25;7(8):1394-1403. doi: 10.1182/bloodadvances.2022009112.
The kinetics of early and late cytomegalovirus (CMV) reactivation after hematopoietic cell transplantation using various methods of graft-versus-host-disease (GVHD) prophylaxis are poorly defined. We retrospectively compared CMV reactivation and disease among 780 seropositive patients given HLA-matched peripheral blood stem cell (PBSC) grafts and calcineurin inhibitor plus posttransplantation cyclophosphamide (PTCy; n = 44), mycophenolate mofetil (MMF; n = 414), or methotrexate (MTX; n = 322). Transplantation occurred between 2007 and 2018; CMV monitoring/management followed uniform standard practice. Hazards of CMV reactivation at various thresholds were compared. Spline curves were fit over average daily viral load and areas under the curve (AUC) within 1 year were calculated. PTCy and MMF were associated with an increased risk of early (day ≤100) CMV reactivation ≥250 IU/mL after multivariate adjustment. The viral load AUC at 1 year was highest with MMF (mean difference = 0.125 units vs MTX group) and similar between PTCy and MTX (mean difference = 0.016 units vs MTX group). CMV disease risk was similar across groups. There was no interaction between GVHD prophylaxis and CMV reactivation on chronic GVHD risk. Despite PTCy-associated increased risk of early CMV reactivation, the CMV disease risk by 1 year was low in HLA-matched PBSC transplant recipients. In contrast, MMF was associated with higher overall CMV viral burden in the 1 year posttransplant. Although different mechanisms of immunosuppressive agents may affect CMV reactivation risk, effective prevention of GVHD may reduce corticosteroid exposure and mitigate infection risk over time.
造血细胞移植后，使用不同方法预防移植物抗宿主病（GVHD）时，早期和晚期巨细胞病毒（CMV）再激活的动力学特征尚未明确。我们回顾性比较了 HLA 匹配的外周血干细胞（PBSC）移植后，接受钙调磷酸酶抑制剂加移植后环磷酰胺（PTCy；n=44）、吗替麦考酚酯（MMF；n=414）或甲氨蝶呤（MTX；n=322）治疗的 780 例 CMV 血清阳性患者的 CMV 再激活和疾病情况。移植发生在 2007 年至 2018 年之间；CMV 监测/管理遵循统一的标准实践。比较了不同阈值下 CMV 再激活的风险。在 1 年内，对平均每日病毒载量和曲线下面积（AUC）进行样条曲线拟合。多变量调整后，PTCy 和 MMF 与早期（第≤100 天）CMV 再激活≥250 IU/mL 的风险增加相关。在 1 年内，MMF 的病毒载量 AUC 最高（与 MTX 组相比，平均差值为 0.125 单位），而 PTCy 与 MTX 相似（与 MTX 组相比，平均差值为 0.016 单位）。各组间 CMV 疾病风险相似。GVHD 预防与 CMV 再激活对慢性 GVHD 风险无相互作用。尽管 PTCy 相关的早期 CMV 再激活风险增加，但 HLA 匹配的 PBSC 移植受者在 1 年内 CMV 疾病风险较低。相比之下，MMF 在移植后 1 年内与更高的 CMV 总病毒负荷相关。尽管免疫抑制剂的不同作用机制可能影响 CMV 再激活的风险，但有效的 GVHD 预防可能会随着时间的推移减少皮质类固醇的暴露并降低感染风险。
