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使用抗胸腺细胞球蛋白会消除无关供体造血干细胞移植后急性髓系白血病患者因巨细胞病毒再激活带来的抗白血病效应。

The use of ATG abrogates the antileukemic effect of cytomegalovirus reactivation in patients with acute myeloid leukemia receiving grafts from unrelated donors.

机构信息

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.

出版信息

Am J Hematol. 2015 Jun;90(6):E117-21. doi: 10.1002/ajh.23998. Epub 2015 Apr 1.

Abstract

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.

摘要

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。

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