Liu Dan, Pei Xuying, Zhang Xiaohui, Xu Lanping, Wang Yu, Yan Chenhua, Chen Huan, Chen Yuhong, Han Wei, Wang Fengrong, Wang Jingzhi, Sun Yuqian, Mo Xiaodong, Huang Xiaojun
National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Peking-Tsinghua Center for Life Sciences, Beijing, 100871, China.
Ann Hematol. 2025 Nov;104(11):5605-5613. doi: 10.1007/s00277-025-06677-4. Epub 2025 Oct 20.
Epstein-Barr virus (EBV) is an important pathogen of infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is also a common cause of secondary hemophagocytic lymphohistiocytosis (sHLH). Thus, we aimed to identify the clinical manifestations and outcomes of EBV-related sHLH after allo-HSCT.
We enrolled the patients who experienced sHLH after EBV DNAemia after allo-HSCT from Jan 1st, 2023 to Dec 31st, 2023. Plasma EBV copies were monitored by Q-PCR analysis at least weekly, and EBV-DNA copies of lymphocyte subpopulations in peripheral blood were also quantified by Q-PCR.
Eleven patients developed sHLH after EBV DNAemia, and all of them had post-transplant lymphoproliferative disorders (PTLD) before sHLH. The median time from PTLD to sHLH occurrence was 5 days (range, 2-101 days). The most common manifestation of sHLH was ferritin elevation (100%) and soluble CD25 antigen elevation (100%). Nine (81.8%) patients died after the diagnosis of sHLH, and the median time from the occurrence of sHLH to death was 10 days (range, 3-21 days). Temperature ≥ 39.6℃, achieving high-level EBV DNAemia (> 10 copies/mL), and a high-level EBV load in T or NK cells increase the risk of sHLH after EBV-PLTD. The 100-day probability of EBV-related mortality and overall survival after PTLD occurrence was 84.1% versus 8.3% (P < 0.0001) and 15.9% versus 91.7% (P < 0.0001), respectively, for patients with and without sHLH.
In summary, our study firstly reported the clinical manifestations and outcomes of EBV-related sHLH following allo-HSCT in the largest cohort at present.
爱泼斯坦-巴尔病毒（EBV）是异基因造血干细胞移植（allo-HSCT）后感染的重要病原体，也是继发性噬血细胞性淋巴组织细胞增生症（sHLH）的常见病因。因此，我们旨在确定allo-HSCT后EBV相关sHLH的临床表现和结局。
我们纳入了2023年1月1日至2023年12月31日期间在allo-HSCT后出现EBV血症后发生sHLH的患者。通过Q-PCR分析至少每周监测血浆EBV拷贝数，并通过Q-PCR对外周血淋巴细胞亚群的EBV-DNA拷贝数进行定量。
11例患者在EBV血症后发生sHLH，且所有患者在发生sHLH之前均有移植后淋巴增殖性疾病（PTLD）。从PTLD到发生sHLH的中位时间为5天（范围2-101天）。sHLH最常见的表现是铁蛋白升高（100%）和可溶性CD25抗原升高（100%）。9例（81.8%）患者在诊断sHLH后死亡，从发生sHLH到死亡的中位时间为10天（范围3-21天）。体温≥39.6℃、达到高水平EBV血症（>10拷贝/mL）以及T或NK细胞中高水平的EBV载量会增加EBV-PLTD后发生sHLH的风险。发生PTLD后，有sHLH和无sHLH患者的EBV相关死亡率和总生存率的100天概率分别为84.1%对8.3%（P<0.0001）和15.9%对91.7%（P<0.0001）。
总之，我们的研究首次在目前最大的队列中报告了allo-HSCT后EBV相关sHLH的临床表现和结局。
