Clinical Characteristics And Prognostic Factors Of Adult Patients With Hemophagocytic Syndrome

Background and ObjectiveHemophagocytic syndrome is known as hemophagocytic lymphohistiocytosis（HLH）which has a high rate of misdiagnosis and mortality.This study is aim to investigate the clinical features and compare the clinical characteristics for the patients with hemophagocytic lymphohistiocytosis（HLH group）and those who not（non-HLH group）.More importantly,to summarize the imaging pictures and gene characteristics,to evaluate the prognostic factors and find out the optimal opportunity of treatment which are crucial for us to improve the survival time and ruduce the mortality rate.Research Content and MethodsThis study retrospectively analyzed 132 patients at the First Affiliated Hospital of Guangzhou Medical University from December 2006 to August 2017.Research Methods:1.132 patients were divided into HLH group and non-HLH group that wered compared by t-test,Chi-square test,Kaplan-Meier survival analysis.2.The Spearman correlation test and the ROC curve were used to find out the optimal critical value of SUV for each tissue.3.The COX regression model,Logsitic regression analysis,Kaplan-Meier survival analysis were performed to discover the prognosis factors and compare the survival time.P value<0.05 has significant statistical differences.Results（I）.The clinical characteristics of patients with hemophagocytosis1.The median age of HLH patients is 44 years.The peak incidence of male patients is between 20-30 and 60-70 years old and the female patients is between 20-30 years old,while other group was 59 years.The main pathogenies in the HLH group were hematological malignancies（49cases;56.32%）and the non-HLH group were infection（19cases;42.22%）.2.The most common symptoms in the HLH group and the non-HLH group were fever.There were significant statistical differences in the symptoms of fever,rash,hepatosplenomegaly（lymphadenopathy）（p<0.05）.3.Elevated ferritin（93.1%）were the main laboratory abnormalities in the two groups.There are significant statistical differences in the white blood cells,platelets,fibrinogen,and serum calcium,PT and APTT,triglycerides,andβ-microglobulin,EB virus,Unknown cells,hepatosplenomegaly,and gene mutation（p<0.05）.4.The median survival time in the HLH group was 12.83 months with the OS rates for 1 and 3 years were 38.27%and 22.22%respectively,while another group was43.33 months with the OS rates were 51.11%and 24.44%respectively.However,there were no statistical difference between the two groups（p=0.191,X²value=1.71）.（II）.The characteristics of imaging and gene with HLH1.The most common imaging abnormalities in patients with HLH were hepatosplenomegaly（64.37%）,followed by pleural effusion（55.17%）.The SUV of lymph node,spleen and bone marrow were positively correlated with Ki-67.The SUV of lymph node and spleen were correlated with EBV quantification.2.The area of SUV _{lymph node},SUV _liver,SUV _spleen and SUV _{bone marrow} under the ROC curve were 0.712,0.788,0.760,and 0.722 respectively,while the best cutoffs were4.75,4.25,4.65 and 3.85 respectively.3.Unidentified cells were found in 30 patients（34.48%）and 20 patients（66.66%）were finally diagnosed as lymphomas.The unidentified cells has statistical significance in the diagnosis of lymphoma-associated hemophagocytic syndrome（L-AHS）（P=0.003）and there was a positive correlation between the number of unidentified cells and Ki-67（p=0.005,r=0.838）.4.Genetic mutations were found in 11 patients which the majority were young men.The highest frequency was STXBP2（90.91%）,followed by UNC13D（45.45%）and LYST（36.36%）.5.The major of laboratory abnormalities in gene-positive patients were elevated sCD25（100%）and positive-EB virus（81.82%）respectively.The mortality rate was81.82%and the main cause was the progression of primary disease（45.45%）.（III）Survival analysis of HLH patients1.Survival analysis between the group of treatment and non-treatment:47patients（54.02%）were treated by chemotherapy（treatment group）and 40 patients（45.98%）were not.Two groups in white blood cell,APTT,D-dimer,EB virus,hepatosplenomegaly had statistical significance（p<0.05）.There were statistical differences in ferritin,white blood cell,platelet,AST,LDH,serum sodium,β-microglobulin,hemophagocytosis and hepatosplenomegaly before and after treatment（p<0.05）.The treatment group’s median survival time and the another was 18.83 and 1.20 months respectively,while has significant difference（p<0.05）.2.Survival analysis of the patients with lymphoma-associated HLH:The prognosis of patients with lymphomas were worse than that of non-lymphomas;the NK/T-LAHS had the worst prognosis which all had statistical significance on the OS（p=0.038;p=0.039）.3.Survival analysis of different treatment for lymphoma-associated HLH:The median survival time of the group A（VP-16+glucocorticoid）,group B（EPOCH,CHOP or ECTOP）,and group C（simple glucocorticoid）was 0.37 months,10.2months,and 0.37 months in the L-AHS.Group B had the best prognosis and 3groups had significant difference（p=0.043）.4.Survival analysis of the patiens with EBV-associated HLH:EBV-positive HLH and EBV-negative HLH;EBV-positive L-AHS and EBV-negative L-AHS had no statistical significance on the OS（p=0.761;p=0.662）.5.Analysis of prognostic factors in patients with HLH:Age（≤40 years）,lymphoma,thrombocytopenia,hyponatremia,ferritin,triglycerides,bilirubin and LDH were unfavorable factors.Age（≤40 years）was the independent risk factor（HR=9.132;95%CI:0.856 to 1.023;p<0.000）.Conclusion1.The majority of adult HLH were young middle-aged men and the common pathogenies were lymphoma.2.PET-CT examination and the unidentified cells played an indispensable role in the differential diagnosis of HLH and L-AHS.3.Genetic mutations may be more likely to occur in young people and the mainly pathogenies were EBV and lymphomas.These patients have rapid disease progression,critical illness,poor prognosis,and high mortality.4.The"EPOCH（CHOP）or ECTOP"regimen given in the first month was the optimal opportunity and protocol for L-AHS patients which had obvious benefits for improving survival time."HLH-1994"protocol and"glucocorticoid"had quite similar effect.5.Age≤40 years was the most unfavorable prognostic factor in HLH.