Clinical presentation and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in China: A retrospective multicenter study

Background: Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous disease with major diagnostic and therapeutic difficulties. A large-scale multicenter study of pediatric HLH is still lacking in China. Procedure: The Histiocytosis Study Group of the Chinese Pediatric Society conducted this retrospective study in 2014. A total of 323 patients diagnosed with HLH between 2011 and 2013 from 12 hospitals were registered. Results: The median age at diagnosis was 2.2 years (range, 0-14.6 years), with a peak age of HLH onset at 0 to 3 years (63%). Mutations in HLH-related genes were found in 27.9% (24/86) patients who underwent genetic testing. PRF1, UNC13D, STXBP2 and LYST were the predominant genes involved. Sixteen patients (66.7%) presented with only monoallelic mutations in one gene. Epstein-Barr virus (EBV) infection was the major condition related to HLH, which was documented in 74.4% (201/270) of the patients who underwent EBV detection. Of 252 evaluable patients, 64.7% (163) achieved non-active disease at the eighth week and patients treated with a protocol containing etoposide presented higher remission rates (75.6% vs. 46.8%, P < 0.001). In multivariate analysis, a younger age at diagnosis (< 12 months), platelet count less than 80x10(9)/L, central nervous system involvement, and initial treatment using a protocol without etoposide (not HLH-94/04) were independent prognostic factors indicating resistant disease. Discussion: This study first multicenter assessment of HLH in China shows some different features in Chinese children with HLH compared with those in western countries, including older age, vulnerability to EBV infection, and a high proportion of patients with single monoallelic genetic mutations.