Department of Oncology and Hematology, Stem Cell Transplant Center, AOU Città Della Salute E Della Scienza, Turin, Italy.
Division of Nuclear Medicine, AOU Città Della Salute E Della Scienza, Turin, Italy.
Am J Hematol. 2015 Jun;90(6):E117-21. doi: 10.1002/ajh.23998. Epub 2015 Apr 1.
Several studies provided evidence of a consistent antileukemic effect induced by cytomegalovirus (CMV) replication in acute myeloid leukemia (AML) patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), however the use of antithymocyte globulin (ATG) as graft-versus-host disease prophylaxis, may potentially abrogate the protective effect of CMV infection. To address this issue, we retrospectively analyzed the risk of relapse in a cohort of 101 patients with AML who received grafts from an unrelated donor after a conditioning regimen including ATG. The cumulative incidence of CMV reactivation, evaluated by RT qPCR, was 59% at 12 months, and 93% of CMV reactivations occurred within the first 100 days post HSCT. The 5-year cumulative incidence of relapse in patients with CMV reactivation was 29% compared with 37% for patients without CMV reactivation, and the only factor associated with a reduced 5-year cumulative incidence of relapse was the disease status at HSCT (P < 0.001). In the multivariable model adverse cytogenetics (HR 2.42, 95% CI 1.02-5.72; P = 0.044) and acute GVHD (HR 3.36, 95% CI 1.32-8.54; P = 0.011) were independent risk factors for reducing overall survival (OS), while the presence of chronic GVHD was associated with a better OS (HR 0.37, 95% CI 0.15-0.89; P = 0.027). CMV replication was not an independent risk factor for OS (HR 1.06, 95% CI 0.07-15.75; P = 0.965). In Conclusion, the results of present study suggest that relapse prevention in patients with AML receiving T-cell depleted HSCT using ATG do not benefit from CMV reactivation.
几项研究提供了证据,表明在接受异基因造血干细胞移植(HSCT)的急性髓系白血病(AML)患者中,巨细胞病毒(CMV)复制可产生一致的抗白血病效应,然而,使用抗胸腺细胞球蛋白(ATG)作为移植物抗宿主病(GVHD)预防,可能会消除 CMV 感染的保护作用。为了解决这个问题,我们回顾性分析了一组 101 例接受无关供体移植的 AML 患者的风险,这些患者在包括 ATG 的预处理方案后接受了移植。通过 RT-qPCR 评估,CMV 再激活的累积发生率在 12 个月时为 59%,93%的 CMV 再激活发生在 HSCT 后 100 天内。CMV 再激活患者的 5 年累积复发率为 29%,而无 CMV 再激活患者的 5 年累积复发率为 37%,与复发率降低相关的唯一因素是 HSCT 时的疾病状态(P<0.001)。在多变量模型中,不良细胞遗传学(HR 2.42,95%CI 1.02-5.72;P=0.044)和急性 GVHD(HR 3.36,95%CI 1.32-8.54;P=0.011)是降低总生存(OS)的独立危险因素,而慢性 GVHD 的存在与更好的 OS 相关(HR 0.37,95%CI 0.15-0.89;P=0.027)。CMV 复制不是 OS 的独立危险因素(HR 1.06,95%CI 0.07-15.75;P=0.965)。总之,本研究结果表明,在接受 ATG 进行 T 细胞耗竭 HSCT 的 AML 患者中,预防复发不应受益于 CMV 再激活。