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 GPBSCs infusion from HLA-mismatched donors after chemotherapy (as GPBSCs group) and sole chemotherapy (as control group) was performed. Efficacy was evaluated 2 and 4 weeks and all patients were followed up until 1 March 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 GPBSCs group, WBC (p=0.017), Fbg (p=0.040), ferritin (p=0.039) improved significantly after treatment. The overall response rate was 66.7% (CR 22.2%, PR 44.4%). However, there is no significant differences in changes of WBC, HGB, PLT, TG, Fbg, Ferritin, AST, ALT, T-bil between two groups. Only the Fbg level was recovered better in the GPBSCs infusion group (p=0.003). In the GPBSCs 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 improve short term survival rate. GPBSCs infusion is suggested as a bridging treatment method to allo-HSCT.