Yue Song1, Jingshi Wang1, Yini Wang1, Zhao Wang2. 1. Department of Hematology, Beijing Friendship Hospital, Capital Medical University, YongAn Road 95th Xicheng District, Beijing, 100050, China. 2. Department of Hematology, Beijing Friendship Hospital, Capital Medical University, YongAn Road 95th Xicheng District, Beijing, 100050, China. wangzhao@ccmu.edu.cn.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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