Recombinant Human Soluble Thrombomodulin is Effective for Severe Childhood EBV-HLH

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disease, presenting with T cell-induced dysregulated cytokine production, systemic inflammation, and frequently intractable coagulopathy. We have administered recombinant human soluble recombinant thrombomodulin (rTM) for four cases of severe childhood Epstein-Barr virus-associated HLH (EBV-HLH) in combination with anti-inflammatory therapy and had good clinical outcomes. To evaluate its efficacy, we retrospectively compared to the former six cases without rTM administration. The patients were admitted between May 2003 and July 2014. The median age at diagnosis was 8.2 years (range, 1.6-16 years). All patients except for two cases without rTM who received only steroid, were treated with steroid, cyclosporine A (CSP) and/or etoposide based on HLH-94 or HLH-2004. All patients receiving rTM were induced in remission. However, two patients without rTM administration died of disease progression. The values of FDP, D-dimer, serum ferritin, and bilirubin improved better in patients with rTM. In some cases without rTM, serum bilirubin increased even though D-dimer, FDP, and ferritin were decreased. Although further clinical experience is required, rTM may be effective as an adjuvant therapy for resolution of severe EBV-HLH.