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血液系统恶性肿瘤患者单倍体外周血干细胞移植后爱泼斯坦-巴尔病毒再激活:免疫重建及其对生存的影响

Epstein-Barr virus reactivation after haplo-peripheral blood stem cell transplantation in patients with hematological malignancies: immune reconstitution and influence on survival.

作者信息

Ma Ling, Zhang Ying, Wang Ting, Cai Yu, Yang Jun, Tong Yin, Huang Chongmei, Qiu Huiying, Zhou Kun, Xu Xiaowei, Niu Jiahua, Shen Chang, Xia Xinxin, Wei Yu, Shao Jie, Yang Min, Cao Jingjing, Song Xianmin, Wan Liping

机构信息

Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China.

出版信息

Ther Adv Hematol. 2025 May 6;16:20406207251335477. doi: 10.1177/20406207251335477. eCollection 2025.

Abstract

BACKGROUND

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a common alternative for patients with hematological malignancies. Epstein-Barr virus (EBV) reactivation is a common complication post-transplantation, but its impact on immune reconstitution and survival remains unclear.

OBJECTIVE

To compare immune reconstitution and survival between patients with and without EBV reactivation after haplo-HSCT.

DESIGN

A retrospective study was conducted involving 322 patients aged 18-60 years, diagnosed with hematological malignancies, who underwent haplo-HSCT at our center from January 2018 to December 2021.

METHODS

Data analysis was performed using SPSS (version 24.0) and R4.3.0 software. Statistical methods included Chi-square tests for qualitative variables, independent tests for continuous variables, Kaplan-Meier method for survival analysis, and logistic regression for risk factor analysis.

RESULTS

After a median of 58 days posttransplant, 176 patients (54.6%) had EBV reactivation, but only 5 patients developed posttransplant lymphoproliferative disorder. Logistics multivariate analysis showed EBV IgA-negative donor, cytomegalovirus (CMV) reactivation, and graft-versus-host disease (GVHD) prophylaxis with anti-thymocyte globulin (ATG) were independent risk factors of EBV reactivation. Then a risk factor prediction model for EBV reactivation after transplantation was established based on the multivariate regression. The analysis based on the generalized linear mixed model showed dramatic improvements in the reconstitution of CD8CD45RO memory T-cells and CD16CD56 NK cells of the EBV-reactivated group. There was no statistical difference in overall survival ( = 0.26), relapse-free survival ( = 0.72), GVHD-relapse free survival ( = 0.44), cumulative incidence of relapse (Gray's test = 0.72), and transplant-related mortality (Gray's test = 0.066) between patients with and without EBV reactivation.

CONCLUSION

Our study showed EBV IgA-negative donor, CMV reactivation, and GVHD prophylaxis with ATG were independent risk factors of EBV reactivation. Posttransplant EBV reactivation had no significant influence on the outcomes of patients, but its impact on immune reconstitution might be complicated. The predictive model based on the study could direct our attention toward patients at high risk of EBV reactivation.

摘要

背景

单倍体相合造血干细胞移植(haplo-HSCT)是血液系统恶性肿瘤患者常用的替代治疗方法。爱泼斯坦-巴尔病毒(EBV)激活是移植后常见的并发症,但其对免疫重建和生存的影响尚不清楚。

目的

比较单倍体相合造血干细胞移植后EBV激活患者与未激活患者的免疫重建和生存情况。

设计

进行一项回顾性研究,纳入2018年1月至2021年12月在本中心接受单倍体相合造血干细胞移植、年龄在18至60岁、诊断为血液系统恶性肿瘤的322例患者。

方法

使用SPSS(24.0版)和R4.3.0软件进行数据分析。统计方法包括定性变量的卡方检验、连续变量的独立样本t检验、生存分析的Kaplan-Meier法以及危险因素分析的逻辑回归。

结果

移植后中位58天,176例患者(54.6%)出现EBV激活,但仅5例发生移植后淋巴细胞增殖性疾病。多因素逻辑回归分析显示,EBV IgA阴性供者、巨细胞病毒(CMV)激活以及使用抗胸腺细胞球蛋白(ATG)预防移植物抗宿主病(GVHD)是EBV激活的独立危险因素。然后基于多因素回归建立了移植后EBV激活的危险因素预测模型。基于广义线性混合模型的分析显示,EBV激活组的CD8CD45RO记忆T细胞和CD16CD56自然杀伤细胞(NK细胞)重建有显著改善。EBV激活患者与未激活患者在总生存(P = 0.26)、无复发生存(P = 0.72)、无GVHD复发生存(P = 0.44)、累积复发率(Gray检验P = 0.72)和移植相关死亡率(Gray检验P = 0.066)方面无统计学差异。

结论

我们的研究表明,EBV IgA阴性供者、CMV激活以及使用ATG预防GVHD是EBV激活的独立危险因素。移植后EBV激活对患者的预后无显著影响,但其对免疫重建的影响可能较为复杂。基于本研究的预测模型可使我们关注EBV激活高危患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad6/12056333/adc276aafe6e/10.1177_20406207251335477-fig1.jpg

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