Analysis of clinical prognosis and mutant gene phenotype in children with hemophagocytic lymphohistiocytosis

Objective To investigate the clinical manifestations, prognosis and gene mutation phenotypes of hemophagocytic lymphohistiocytosis(HLH)in children of our hospital. Methods The clinical data of 42 patients with HLH from April 2013 to December 2018, and the genetic data of 8 patients with familial HLH(FHL)were collected retrospectively.The age, clinical manifestation, laboratory examination, prognosis and the characteristics of gene mutation phenotype of patients with HLH and FHL were analyzed emphatically.Furthermore, the clinical manifestations and prognosis of patients with HLH were analyzed according to whether EB virus was infected. Results Among these 42 patients with HLH, the onset age was ranged from 1 month to 13 years old and most of them were younger than 5 years old.The main clinical manifestations included cytopenia, prolonged fever, enlargement of liver and spleen and lymph nodes enlargement and serosal effusion.Laboratory examination showed that lactate dehydrogenas, ferritin, erythrocyte sedimentation rate and triglyceride increased significantly.The survival rate of the group in ferritin exceeding 4 500 μg/L and non-chemotherapy was lower than that of the group of ferritin less than 4 500 μg/L and chemotherapy in clinical prognosis(P<0.05). Ten patients of them survived after chemotherapy, and 2 patients survived for 5 to 6 months after hematopoietic stem cell transplantation in FHL.Patients with EB virus infection were older than those without EB virus infection.They had longer fever duration and higher proportion of lymph nodes enlargement and ferritin more than 4 500 μg/L(P values were 0.01, 0.04, 0.03, 0.03 respectively). However, there was no significant difference in survival time between the two groups.Eight patients had mutations in UNC13D(50.00%), PRF1(25.00%), PRKDC(12.50%)and IL2RG(12.50%)genes respectively, and most of the mutations were complex heterozygous mutations(62.50%). All the mutations were originated from their parents. Conclusion HLH is characterized by cytopenia, prolonged fever, enlargement of liver and spleen.HLH is more common in children under 5 years old.The clinical manifestations of HLH with EB virus infection are more severe while the prognosis is not statistically significant.The incidence of FHL is higher.There are more UNC13D gene mutations and complex heterozygous mutations.Children with HLH should be detected and treated with standardized therapy as soon as possible.Hematopoietic stem cell transplantation is a good treatment for HLH, especially for FHL patients. Key words: Hemophagocytic syndrome; Exon sequencing; Gene mutation; EB virus infection; Prognosis