Long-term Clinical Report On The Effect Of Combined Immunosuppression Therapy On Aplastic Anemia In Children

Purpose:Through the analysis of the clinical data of acquired aplastic anemia(AA)in children with combined immunosuppressive therapy(IST),the efficacy and prognostic factors of IST in children with AA were summarized,as well as the transformation of the clone of paroxysmal sleep hemoglobinuria(PNH).Methods:From June 2009 to August 2019,59 children with AA who were diagnosed as AA by blood routine,bone marrow morphology and bone marrow pathology in the second affiliated hospital of anhui medical university and received rabbit ATG combined with CSA were selected as the study objects.Retrospective analysis was made on the clinical data of 59 children with AA,as well as the changes of T cell subsets in different disease stages of children with AA,to summarize and analyze the effect of IST on children with AA and the long-term follow-up results.PNH clonal transformation in 38 AA children was followed up in the long term.SPSS16.0 statistical software was used for data analysis,and t-test was used for comparison between t-cell subsets at different stages of treatment response.The chi-square test was used to analyze the single factor of infection,serum disease,severity of different diseases,lymphocyte count,reticulocyte count and other influencing factors of efficacy.Results:Among the 59 children newly diagnosed with AA,there were 35 cases of severe aplastic anemia(SAA),18 cases of severe aplastic anemia(VSAA)and 6 cases of non-severe aplastic anemia(NSAA).The median follow-up was 24 months(6-96months).(1)The effective rate was 22%one month after IST,39%after 3 months,57%after6 months,61%after 9 months,71%after 12 months and 71%at the end of follow-up.By June 2019,18 children with AA were followed up for 5 years,and the 5-year event-free survival rate of these 18 children with AA was 66%.(2)The results of single factor analysis showed that whether there was infection before treatment,whether there was serum disease during IST,disease severity,lymphocyte count and reticulocyte count at the first diagnosis had no significant correlation with the efficacy.(3)The proportions of CD3~+T cells and CD4~+T cells were 82.34±10.36 and38.90±9.50 after treatment,respectively,which were significantly higher than74.20±10.25 and 28.71±10.22 before treatment,with statistically significant differences(T value=3.136,P=0.006.T value=3.744,P=0.002),the proportion of CD8~+T cells decreased significantly,and the CD4~+T/CD8~+T ratio increased significantly(P<0.05).Th17 and Treg cells were detected in 43 children with AA at three time points of initial diagnosis,partial response and complete response.The statistical results showed that the proportion of Th17 cells decreased significantly after IST,and the difference of Th17cell proportion D in AA children at different treatment stages was statistically significant(P<0.05).After IST,Th17/Treg was 0.23,while before treatment was 0.51,which was significantly higher after treatment than before treatment,and the difference was statistically significant(P<0.05).IST can improve the immune function of children with AA.(4)PNH cloning of 38 children with AA was followed up,and it was found that 11children with AA had positive PNH cloning in the first diagnosis of AA.There was no difference in IST response rate and overall survival rate among AA patients with or without PNH cloning at first diagnosis.All of the 11 children turned negative in PNH cloning three months after IST.However,there were 2 cases of PNH clone negative AA children with PNH conversion to Yang at 3 months after IST and to Yin at 6 months after IST.Conclusion:In this study,59 cases of children with AA who underwent IST were studied,and the total effective rate reached 71%.The effect of IST on children with AA was accurate and the prognosis was good.For AA patients with no fully compatible sibling donor,IST is the first and important treatment plan.After IST,the proportion of CD4+T in children with AA increased,the proportion of CD8+T decreased,and the number of CD4+T/CDB+T increased,while the number of Th17 cells decreased and Th17/Treg decreased.IST can correct the immune imbalance and improve the immune function of patients with AA.This study found that there was no direct relationship between the incidence of infection before treatment,the occurrence of serum disease,the severity of the disease,lymphocyte count and reticulocyte count before treatment and the efficacy of IST In treating AA in children.In this group,11 children(28%)had PNH cloning at the first diagnosis of AA,and the effect of PNH cloning positive and PNH cloning negative on the efficacy was statistically insignificant,but it can still give us a hint that PNH cloning positive children may be more efficient.The progress of PNH cloning in this group was significantly lower than that in adults,and only 1 patient with AA was transformed into aa-pnh syndrome after IST.IST is effective in treating AA in children,and can effectively improve the cellular immune function of children with AA.PNH cloning was found in some children with AA at the first diagnosis,and IST with or without PNH cloning did not affect the efficacy of IST.