Outcomes In Children With Hemophagocytic Lymphohistiocytosis Treated Using HLH-2004 Protocol In A Single Center

Objectiv:To investigate the clinical characteristics of hemophagocytic lymphohistiocytosis(HLH),to analyze the outcome of HLH-2004 protocol and the prognostic factors of HLH patients.Methods:We conducted a prospective study of HLH patients who received treatment following HLH-2004 protocol in the Children's Hospital affiliated with Chongqing Medical University between January,2009 and June,2017.The clinical and laboratory findings were statistically analyzed and the cumulative survival curves were described following the Kaplan–Meier method.Prognostic factors were analyzed following COX multivariate regression.Results:A total of 149 patients,67 male and 82 female,were recruited.Median age of the patients at onset was 42 months(range 7-189).The3-year overall survival rate was 78.5%.All of the patients exhibited fever,hypofibrinogenemia,highlevelofferritin,98.7%exhibited hepatosplenomegaly,94.6%exhibited cytopenias,79.9%exhibited hepatitis.Gene sequencing analysis was carried out in 57 patients.Genetic variants were observed in 61.4%patients.45.7%exhibited variants in UNC13D.37.1%exhibited variants in STXBP2.31.4%exhibited variants in ITK and 37.1%in LYST.A Few of them carried variants in PRF(N=1),STX11(N=1)and AP3B1(N=2).26.8%patients reported neurological alterations at onset,characterised by seizures,reduced level of consciousness,brain atrophy and lesions.28.9%patients relapsed.Four patients relapsed in the fifth.four relapsed in the eighth week of initial therapy.20 in the first and second week off therapy.Carrying HLH-related gene variants was the risk factor of relapse(P=0.030).Thirty-two patients died and severe bleeding as well as disease progression contribute to most of the deaths.43.8%(N=14)patients died in the first 2 weeks of initial therapy.Relapse was the risk factor of death(X~2=3.961,P=0.048)but the frequency or times of relapse show no relevance with death.Age at onset and neurological alterations in radiologist and cerebrospinal fluid showed no significant relevance with death.Conclusion:HLH-2004 protocol had a good prognosis with a 3 years OS of 78.5%.Patients with HLH gene mutations would be a 452.2%increase in risk for relapse.Relapse was a risk factor for death.