Shi Lin, Dou Liurui, Wang Jingshi, Wang Zhao
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Hematology. 2025 Dec;30(1):2503745. doi: 10.1080/16078454.2025.2503745. Epub 2025 May 13.
X-linked inhibitor of apoptosis protein (XIAP) deficiency is a congenital immunodeficiency disorder characterized by increased susceptibility to Epstein-Barr virus (EBV) infection and is frequently associated with hemophagocytic lymphohistiocytosis (HLH).
To investigate the correlation between EBV and XIAP deficiency-related HLH, including EBV infection status, XIAP genetic mutation sites, and the efficacy of different treatment regimens in patients with EBV-positive XIAP deficiency-related HLH, and to analyse the prognosis of these patients.
We retrospectively analysed patients diagnosed with EBV-positive XIAP deficiency-related HLH.
Data were collected from August 2017 to August 2024, and 10 patients were included in this study. All patients exhibited an elevated EBV-DNA load. EBV-DNA was detected in both plasma (2/10) and peripheral blood mononuclear cells (10/10), specifically B cells (9/9) and T cells (4/9). Treatment regimens containing rituximab, HLH-2004, and dexamethasone with or without ruxolitinib achieved complete remission. However, only the regimen containing rituximab successfully eradicated EBV from plasma and peripheral blood mononuclear cells in all patients. None of the patients underwent allogeneic haematopoietic stem cell transplantation. No cases of HLH recurrence or EBV reactivation were observed during a median follow-up of 28 months.
EBV infection plays a crucial role in triggering HLH in patients with XIAP deficiency. XIAP deficiency-related HLH is frequently associated with EBV infection, which predominantly affects B cells. Treatment regimens containing rituximab can effectively control HLH and eliminate EBV infection. Allogeneic haematopoietic stem cell transplantation may be avoidable in paediatric patients achieving EBV eradication through rituximab-containing regimens.
X连锁凋亡抑制蛋白（XIAP）缺乏是一种先天性免疫缺陷疾病，其特征为对爱泼斯坦-巴尔病毒（EBV）感染的易感性增加，且常与噬血细胞性淋巴组织细胞增生症（HLH）相关。
探讨EBV与XIAP缺乏相关HLH之间的相关性，包括EBV感染状态、XIAP基因突变位点，以及EBV阳性XIAP缺乏相关HLH患者不同治疗方案的疗效，并分析这些患者的预后。
我们回顾性分析了诊断为EBV阳性XIAP缺乏相关HLH的患者。
收集了2017年8月至2024年8月的数据，本研究纳入了10例患者。所有患者的EBV-DNA载量均升高。血浆（2/10）和外周血单个核细胞（10/10）中均检测到EBV-DNA，具体为B细胞（9/9）和T细胞（4/9）。含利妥昔单抗、HLH-2004以及地塞米松（联合或不联合鲁索替尼）的治疗方案实现了完全缓解。然而，只有含利妥昔单抗的方案在所有患者中成功从血浆和外周血单个核细胞中清除了EBV。所有患者均未接受异基因造血干细胞移植。在中位随访28个月期间，未观察到HLH复发或EBV重新激活的病例。
EBV感染在引发XIAP缺乏患者的HLH中起关键作用。XIAP缺乏相关HLH常与EBV感染相关，EBV主要影响B细胞。含利妥昔单抗的治疗方案可有效控制HLH并消除EBV感染。对于通过含利妥昔单抗方案实现EBV清除的儿科患者，可能无需进行异基因造血干细胞移植。
