Requirement for containing etoposide in the initial treatment of lymphoma associated hemophagocytic lymphohistiocytosis

Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory status caused by a hereditary or acquired immunoregulatory abnormality. Lymphoma associated hemophagocytic lymphohistiocytosis (LAHS) is a kind of secondary HLH (sHLH). It has the worst prognosis among sHLH. However, there’s still no standard treatment strategy. The argument mainly focuses on whether an HLH-directed or malignancy-directed approach should initially be adopted. Etoposide is one of the key drugs in HLH treatment, also effective in lymphomas. We sought to identify the importance of containing etoposide in initial treatment, comparing with the chemotherapy which directed at lymphoma but without etoposide. Methods: 66 patients diagnosed as LAHS in our center between Jan 1 2015 and Dec 31 2017 were divided into two groups according to weather the initial treatment containing etoposide, or other lymphoma-directed chemotherapy without etoposide. Results: The remission rate of the initial etoposide group (52 patients) is significantly better than that of no initial etoposide group (14 patients) (73.1% vs. 42.9%, p=0.033). The 2-month survival rate (79.8% vs. 46.8%, p=0.035) and overall survival (median survival time 25.8w vs. 7.8w, p=0.048) of the initial etoposide contained group is significantly better. Multivariate cox analysis revealed that for patients without EBV infection (37 cases), initial treatment with etoposide could significantly improve prognosis (p=0.010, Exp(B)=0.183), but for patients with positive EBV, it’s not significant. Conclusions: Containing etoposide is beneficial in the initial treatment of LAHS, weather using the HLH directed or lymphoma directed strategy. It provides higher response rate, lower mortality rate and better survival, especially for EBV negative patients.