Retrospective And Predictive Analysis Of 24 Children With Malignancy-associated Haemophagocytic Lymphohistiocytosis

BackgroundHemophagocytic syndrome(HPS)is also called hemophagoeytic lymphohistiocytosis(HLH),which is immuno-inflammatory responses that caused by lmphocytes and macrophages are hyperactive and produce large amounts of inflammatory cytokines.Clinical features include persistent fever,hepatosplenomegaly,the reduction of blood cells,abnormal liver function and coagulopathy.The onset age can be seen in all age groups,but it is common in children.According to the etiology,there are two major categories: primary HPS and secondary HPS.Malignancy-associated hemophagocytic lymphohistiocytosis(MAHS),belongs to a kind of secondary HPS,with low incidence and mostly in adulthood.MAHS is a serious diseasewith multiple complications and rapid change,the mortality were very high.The pathogenesis of MAHS is not clear,which may be associated with the increase of tumor load or the immune suppression caused by chemotherapy,and that leads to the immune dysfunction,causing the occurrence of cytokine storm.MAHS can be divided into two types of one is considered triggered by the malignancy(M-HPS)and the other occurred during chemotherapy(Ch-HPS).In addition to the symptoms of the malignancy itself,there are also symptoms associated with HPS.Because HPS symptoms are serious,they may even cover up the symptoms of malignant tumor.The treatment of MAHS has the characteristics of individuation and stage,and there is no standard treatment program.At present,the reports about MAHS mainly around adult cases in China,children's reports are relatively rare.This study retrospectively analyzed 24 children's MAHScases of the clinical characteristics,treatment and prognosis,which datas come from the first affiliated hospital of zhengzhou university children's hospital in recent 6 years.And we aimed at improving the clinician awareness of the disease.MethodsWeobserved24 cases of malignancy-associatedhemo-phagocytic lymphohistiocytosis(MAHS)in our hospital during the period from June 2011 to January 2017,and collected information about MAHS:clinical characteristics,laboratory examinations,treatmentand survival.ResultsAmong the 24 patients,the onset age was 18 months to 15 years and 6 months,and the median age was 4 years and 4 months,15 males(62.5%)and 9 females(37.5%).11 cases(45.8%)were triggered by the malignancy(M-HPS),and 13(54.2%)were occurred during chemotherapy(Ch-HPS).Malignant tumor: 17 cases(70.8%)were acute leukemia;6 cases(25%)were lymphoma;1 case(4.2%)was neuroblastoma.Fever(100%,24/24),respiratory symptoms(91.7%,22/24)and hepatomegaly(55.2%,24/24)were the most common clinical symptoms.The remaining common clinical manifestations are in turn include splenomegaly(50%,12/24),serous cavity effusion(45.8%,11/24),lymphadenopathy(41.7%,10/24),skin purpura(25%,6/24),jaundice(12.5%,3/24),nervous system symptom(12.5%,3/24).Decrease of 2 lineages cell in the peripheral blood(100%,24/24),hyperferritinaemia(91.7%,22/24)and lactate dehydrogenase levels(87.5%,21/24)were the first three common laboratory findings.Other laboratory abnormalities include elevated CRP levels(79.2%,19/24),hemophagocytosis in bone marrow(70.8%,17/24),liver dysfunction(62.5%,15/24),hypertriglyceridemia and/or hypofibrinogenemia(54.2%,13/24),EB virus DNA quantitative increasing(8.3%,2/24).22 cases were treated with HLH-2004 protocol,and 2 patients were given treatment,including 18 cases of death,5 cases of survival and 1 cases of missing visit.Median survival time is 28 days(28 days to 2 years and 4 months).Conclusions1.Children's MAHS were most common in acute leukemia and lymphoma.2.The HPS occurred during chemotherapy is not limited to the intensive treatment stage,but also needs to be vigilant during the maintenance treatment stage.3.For children with EBV-HPS,if HPS and antiviral treatment is not effective and the condition is repeated,genetic screening should be carried out to exclude family hemophagocytic reticulosis,and the lymphoma is highly vigilant.4.There is no standard treatment program for MAHS,whether the initial treatment should be aimed at HPS or malignant tumor,or bothhave no verdict.Due to the difference in the basic diseases?disease stage and Severity?genetic background and drug interactions of individuals,its treatment also has the characteristics of individuation and phase change,should be timely monitoring and assessment,constantly adjust the treatment program.