Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory state. Epstein–Barr virus (EBV) infection-associated HLH (EBV-HLH) is one of the most common secondary HLH and suffers a very poor prognosis. Allo-HSCT is often required for refractory EBV-HLH, but some patients still cannot proceed to the next allo-HSCT due to various factors. This study aimed to observe the efficacy of HLA-mismatched granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (GPBSCs) infusion for refractory EBV-HLH. A retrospective case-control study of refractory EBV-HLH patients with GPBSC infusion from HLA-mismatched donors after chemotherapy (as GPBSC group) and sole chemotherapy (as control group) was performed. Efficacy was evaluated 2 and 4 weeks and all patients were followed-up until March 1, 2018. There were 18 cases who accepted infusion between March 2016 and Sep 2017 and 19 were randomly selected from refractory EBV-HLH patients who underwent salvage therapy during the same period for the control group. In GPBSC group, WBC (p = 0.017), Fbg (p = 0.040), and ferritin (p = 0.039) improved significantly after treatment. The overall response rate was 66.7% (CR 22.2%, PR 44.4%). However, there are no significant differences in changes of WBC, HGB, PLT, TG, Fbg, Ferritin, AST, ALT, and T-bil between two groups. Only the Fbg level was recovered better in the GPBSC infusion group (p = 0.003). In the GPBSC group, EBV-DNA decreased significantly after 2 weeks (p = 0.001) and 4 weeks (p = 0.012) after treatment, and the effect of the decrease was significantly better than that of the chemotherapy alone group in 2 weeks but not 4 weeks (p2w = 0.011, p4w = 0.145). The median survival time in the infusion group was 20.4 weeks [95% CI 10.9, 29.9], and the median survival time in the control group was 10.8 weeks [95% CI 0–24.34]. In the short-term, the infusion group’s survival rate was better (2-month 88.89% vs. 52.63%, p = 0.008; 3-month 83.33% vs. 47.09%, p = 0.012), but there was no difference in OS (p = 0.287). Infusing GPBSCs combined with chemotherapy is effective, especially in decreasing EBV-DNA, performs better than chemotherapy alone, and improves short-term survival rate. GPBSC infusion is suggested as a bridging treatment method to allo-HSCT.

中文翻译：

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HLA不匹配的GPBSC输注治疗难治性爱泼斯坦-巴尔病毒相关的吞噬性淋巴细胞组织细胞增生症：来自单个中心的观察性研究。

吞噬淋巴细胞组织细胞增生症（HLH）是一种严重甚至致命的炎症状态。与爱泼斯坦-巴尔病毒（EBV）感染相关的HLH（EBV-HLH）是最常见的继发性HLH之一，其预后很差。难治性EBV-HLH通常需要用allo-HSCT，但是由于各种因素，一些患者仍无法进行下一次allo-HSCT。这项研究旨在观察HLA不匹配的粒细胞集落刺激因子（G-CSF）动员的外周血干细胞（GPBSCs）输注对难治性EBV-HLH的疗效。一项回顾性病例对照研究是对难治性EBV-HLH患者进行化疗（作为GPBSC组）和单独化疗（作为对照组）后，从HLA不匹配的供体中注入GPBSC。在第2周和第4周评估疗效，并对所有患者进行随访直至2018年3月1日。在2016年3月至2017年9月之间有18例接受输注的病例，对照组中同期从19例接受挽救治疗的难治性EBV-HLH患者中随机选择了19例。在GPBSC组中，治疗后WBC（p = 0.017），Fbg（p = 0.040）和铁蛋白（p = 0.039）显着改善。总体缓解率为66.7％（CR 22.2％，PR 44.4％）。但是，两组之间的WBC，HGB，PLT，TG，Fbg，铁蛋白，AST，ALT和T-bil的变化没有显着差异。在GPBSC输液组中，仅Fbg水平恢复得更好（p = 0.003）。在GPBSC组中，治疗后2周（p = 0.001）和4周（p = 0.012）后EBV-DNA显着下降，并且下降的效果明显优于单纯化疗组，但在2周后没有下降。 4周（p2w = 0.011，p4w = 0.145）。输液组的中位生存时间为20.4周[95％CI 10.9，29.9]，而对照组的中位生存时间为10.8周[95％CI 0-24.34]。在短期内，输液组的存活率更好（2个月88.89％比52.63％，p = 0.008； 3个月83.33％vs 47.09％，p = 0.012），但OS并无差异（p ＝ 0.287）。将GPBSCs与化学疗法相结合是有效的，尤其是在减少EBV-DNA方面，比单独使用化学疗法效果更好，并且可以提高短期生存率。建议将GPBSC输注作为异体HSCT的桥接治疗方法。输注组的生存率更好（2个月88.89％比52.63％，p = 0.008； 3个月83.33％vs. 47.09％，p = 0.012），但OS差异无统计学意义（p = 0.287）。将GPBSC与化学疗法相结合是有效的，尤其是在降低EBV-DNA方面，比单独使用化学疗法效果更好，并且可以提高短期生存率。建议将GPBSC输注作为异体HSCT的桥接治疗方法。输注组的生存率更好（2个月88.89％比52.63％，p = 0.008； 3个月83.33％vs. 47.09％，p = 0.012），但OS没有差异（p = 0.287）。将GPBSC与化学疗法相结合是有效的，尤其是在降低EBV-DNA方面，比单独使用化学疗法效果更好，并且可以提高短期生存率。建议将GPBSC输注作为异体HSCT的桥接治疗方法。