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血液恶性肿瘤患者行单倍体相合与同胞相合 PBSCT 后 EBV-DNA 血症和移植后淋巴增殖性疾病的危险因素和临床结局。

Risk factors and clinical outcomes of Epstein-Barr virus DNAemia and post-transplant lymphoproliferative disorders after haploidentical and matched-sibling PBSCT in patients with hematologic malignancies.

机构信息

Department of Hematology, Chinese PLA General Hospital, Medical School of Chinese PLA, 28 Fuxing Road, Beijing, 100853, China.

Institute of Basic Medicine, Chinese PLA General Hospital, Medical School of Chinese PLA, 28 Fuxing Road, Beijing, 100853, China.

出版信息

Ann Hematol. 2019 Sep;98(9):2163-2177. doi: 10.1007/s00277-019-03742-7. Epub 2019 Jun 26.

Abstract

In allogeneic hematopoietic stem cell transplantation recipients, reactivation of Epstein-Barr virus (EBV) can cause post-transplantation lymphoproliferative disorder (PTLD), which may rapidly progress to multiorgan failure and even death. Development of EBV PTLD correlates very closely with use of anti-thymocyte globulin (ATG) and type of transplant. To assess the incidences and clinical features of EBV DNAemia and PTLD in the setting of stem cell transplantation using unmanipulated G-CSF-primed allogeneic peripheral blood stem cells as graft, we performed a retrospective analysis of stem cell transplantation from HLA-matched sibling donors (MSD-SCT, n = 90) or HLA-haploidentical related donors (HID-SCT, n = 110) in patients with hematological malignancies. All of HID-SCT recipients and 27.8% of MSD-SCT recipients received an ATG-containing conditioning regimen. One-year cumulative incidence of EBV DNAemia was 44.1%, ranging from 4.8% in MSD-SCT recipients not using ATG to 20.0% in MSD-SCT recipients using ATG, and 73.7% in HID-SCT recipients. Risk factors for EBV reactivation included use of ATG (p = 0.008), male donor (p = 0.034), and cytomegalovirus DNAemia (p < 0.001). One-year incidence of EBV PTLD was 11.9%, ranging from 1.8% in recipients of MSD-SCT not using ATG to 4.4% in recipients of MSD-SCT using ATG, and 23.5% in recipients of HID-SCT. Risk factors for PTLD after HID-SCT included in fludarabine-containing conditioning regimen (p = 0.010), cytomegalovirus DNAemia (p = 0.036), and patient's age < 40-yr (p = 0.032). Two-year non-relapse mortality was higher for patients with EBV DNAemia than those without EBV DNAemia (35.8% vs. 15.3%, p = 0.002). One-year relapse-free survival and overall survival among patients with PTLD were 40.2% and 44.9%, respectively, as opposed to 63.4% and 68.4% among patients without PTLD (both p < 0.05). In multivariate analyses, EBV DNAemia predicted a lower risk of relapse (p = 0.025), while PTLD was a marginally significant predictor of relapse (p = 0.092). This study identified patients at risk of EBV reactivation and PTLD after unmanipulated allogeneic peripheral blood stem cell transplantation.

摘要

在异基因造血干细胞移植受者中,EB 病毒(EBV)的再激活可导致移植后淋巴组织增生性疾病(PTLD),其可能迅速进展为多器官衰竭,甚至死亡。EBV PTLD 的发展与使用抗胸腺细胞球蛋白(ATG)和移植类型密切相关。为了评估未经过处理的 G-CSF 预处理的同种异体外周血造血干细胞作为移植物的干细胞移植中 EBV DNAemia 和 PTLD 的发生率和临床特征,我们对来自 HLA 匹配的同胞供体(MSD-SCT,n=90)或 HLA 单倍体相关供体(HID-SCT,n=110)的血液系统恶性肿瘤患者的干细胞移植进行了回顾性分析。所有 HID-SCT 受者和 27.8%的 MSD-SCT 受者接受了含 ATG 的预处理方案。EBV DNAemia 的 1 年累积发生率为 44.1%,范围从未使用 ATG 的 MSD-SCT 受者的 4.8%到使用 ATG 的 MSD-SCT 受者的 20.0%,以及 HID-SCT 受者的 73.7%。EBV 再激活的危险因素包括使用 ATG(p=0.008)、男性供者(p=0.034)和巨细胞病毒 DNAemia(p<0.001)。EBV PTLD 的 1 年发生率为 11.9%,范围从未使用 ATG 的 MSD-SCT 受者的 1.8%到使用 ATG 的 MSD-SCT 受者的 4.4%,以及 HID-SCT 受者的 23.5%。HID-SCT 后发生 PTLD 的危险因素包括含氟达拉滨的预处理方案(p=0.010)、巨细胞病毒 DNAemia(p=0.036)和患者年龄<40 岁(p=0.032)。与无 EBV DNAemia 的患者相比,有 EBV DNAemia 的患者 2 年非复发死亡率更高(35.8%比 15.3%,p=0.002)。PTLD 患者的 1 年无复发生存率和总生存率分别为 40.2%和 44.9%,而无 PTLD 患者分别为 63.4%和 68.4%(均 p<0.05)。多变量分析表明,EBV DNAemia 预测复发风险较低(p=0.025),而 PTLD 是复发的边缘显著预测因素(p=0.092)。这项研究确定了未经过处理的同种异体外周血造血干细胞移植后 EBV 再激活和 PTLD 的高危患者。

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