Clinical Analysis Of Thrombotic Microangiopathy After Allogeneic Hematopoietic Stem Cell Transplantation In Children

Objective To investigate the clinical features of thrombotic microangiopathy associated with allogeneic hematopoietic stem cell transplantation in children.Explore the dynamic change of plasma human terminal complement complex C5b-9 concentration with TA-TMA and correlation of TA-TMA susceptibility genes with TA-TMA.Methods A retrospective analysis of continuous clinical data from HSCT received in the Department of Hematology and Oncology of Wuhan Children’s Hospital from August 1,2016 to June 30,2022.Results From August 2016 to June 2022,a total of 244 children underwent hematopoietic stem cell transplantation in the Department of Hematology and Oncology of Wuhan Children’s Hospital,of which 229 patients were included in the study.A total of 23 patients were diagnosed with TA-TMA and treated accordingly,with a prevalence of 10.0%and a male-to-female ratio of 13:10.The median diagnosis of TA-TMA was 83(7-289)days after HSCT,with early TA-TMA in 14(60.9%)patients and delayed TA-TMA in 9(39.1%)patients.The primary disease types were aplastic anemia 8(34.8%)cases,acute myeloid leukemia 4(17.4%)cases,and hemophagocytic syndrome 3(13.0%)cases.Clinical manifestations: 23 cases had progressive decline of platelets,of which 19 cases were ineffective platelet transfusion,20 cases had bleeding of varying degrees,mainly manifested in skin and mucous membrane,gastrointestinal tract and urinary tract bleeding,and the blood pressure of 21 patients was higher than that of children of the same age,sex and height.After treatment,6 cases survived,and the overall mortality rate was 73.9%,and 13 deaths due to TA-TMA had a mortality rate of 56.5%.Comparison of s C5b-9 levels before and after transplantation in children with TA-TMA showed that plasma s C5b-9 concentration was positively correlated with TA-TMA disease(P<0.05).Each 1 ng/ml increase in plasma s C5b-9 concentration increased the risk of TA-TMA by 1.3%.When the concentration of s C5b-9 ≥ 344.67 ng/ml,its discriminating effect was 0.934(95% CI=0.872-0.996),and the sensitivity of TA-TMA was 94.1% and the specificity was 89.8%.Of the 66 children tested for TA-TMA susceptibility genes,55(83%)had at least one gene variant identified.Mutation sites mostly appeared in the four genes of ADAMTS13,CD46,CFI,and CFH.Mutated genes were present in all 5 patients with TA-TMA,with a median number of mutations of 2(1-5).Due to the small number of patients who developed TA-TMA in this test,the prevalence of TA-TMA was not related to the frequency of mutation in patients without further statistical analysis.Conclusion: TA-TMA is a serious complication after HSCT and has a high mortality rate upon diagnosis.Unexplained rapid platelet decline or ineffective platelet transfusion are the earliest symptoms of TA-TMA in children.Plasma s C5b-9 concentrations in children with allo-HSCT were positively correlated with TA-TMA.When the plasma s C5b-9concentration≥344.67 ng/ml,the diagnostic sensitivity and specificity of TA-TMA are high,and monitoring its concentration can help diagnose TA-TMA in children,but whether it is helpful to predict prognostic risk still needs to be further verified by multicenter large samples.Patients with TA-TMA have TA-TMA susceptibility gene mutations,but whether this mutation directly or indirectly causes the disease is still unclear.We look forward to future multi-center and large-sample research.