Analysis Of Factors Related To The Efficacy Of Immunosuppressive Therapy In 112 Children With Acquired Aplastic Anemia

Backround:Aplastic anemia is a blood disease characterized by immune factor mediated bone marrow hematopoiesis failure and whole blood cytopenia.Combined immunosuppressive therapy(IST)that anti-thymocyte globulin(ATG)combined with cyclosporine(CsA)is the first choice for the treatment of severe aplastic anemia(SAA)and very severe aplastic anemia(vSAA)in children without suitable hematopoietic stem cell donors.About 1/3 patients with IST were not effective.It is necessary to find effective predictors of therapeutic effect to make the choice of immunosuppressive therapy more reasonable and to further improve the efficacy of immunosuppressive therapy.Objective:The aim of this study is to explore the related factors influencing the efficacy of immunosuppressive therapy,so as to provide references for further clinical treatment.Methods:The clinical data of 112 children with acquired aplastic anemia who were treated with IST(rabbit-ATG combined with CsA)during January 2014 to June 2017 in the first affiliated Hospital of Zhengzhou University were analyzed retrospectively.31cases with non-severe aplastic anemia,52 cases with severe aplastic anemia,and 29cases with severe severe aplastic anemia,aged 1-14 years,were divided into effective group and ineffective group according to the follow-up results of 6 months after IST.The criteria for judging the effect were based on the recommendations of the Chinese Journal of Pediatrics on the diagnosis and treatment of childhood acquired aplastic anemia published on 2014,and collected the general data,laboratory indicators,and so on before IST.Analyze the difference of clinical baseline data between effective group and ineffective group,and analyze the correlation between clinical data and IST effect.Results:1.Total 64 cases of complete remission and partial remission were obtained,48cases without remission,the effective rate of IST is 57%(64/112 cases)2.The sex distribution and type of aplastic anemia in the effective group and ineffective group were not statistically significant(P>0.05).The median age of the effective group was 6.0(3.0-9.0)years old,the median age of the ineffective group was 8.0(4.0-12.0)years old,there is not significant difference of these two groups(P=0.058).The median of ANC in effective group was 0.51×10~9/L,ANC in ineffective group was 0.23×10 ~9/L,median of Ret in effective group was 21.7×10~9/L,median of Ret in ineffective group was 17.3×10~9/L,the above two indexes were statistically significant in both groups.The median hematopoiesis area of bone marrow was40.0%in the effective group and 14.0%in the ineffective group(P<0.001).3.The area under the ROC curve of bone marrow biopsy hematopoiesis,reticulocyte count and absolute neutrophil count for evaluating the curative effect of IST were 0.772(95%CI:0.629-0.915,P<0.001),0.726(95%CI:0.591-0.862,P=0.003)and 0.666(95%CI:0.524-0.808,P=0.032).The optimal limit values of ROC curves is24%?17.5×10~9/L and 0.3×10~9/L.4.Univariate regression analysis showed that there was no correlation between IST efficacy and aplastic anemia in sex and age and the treatment time of IST(P>0.05).High level of bone marrow biopsy hematopoiesis area,ANC and Ret were the predictors of hematological response in IST(P<0.05).Multivariate Logistic regression analysis showed that bone marrow hematopoiesis area(>24%)and Ret(>17.5×10 ~9/L)were independent protective factors for hematological response after IST.5.At different ages,bone marrow hematopoiesis area has medium predictive value for IST effect.The optimal limit of ROC volume curve for bone marrow hematopoietic area evaluation in aplastic children with aged 1-3 years old was18%.The optimal limit value of the ROC volume curve of bone marrow hematopoietic area in children aged 4-7 years old was 21%.The optimal boundary value of bone marrow hematopoietic area in children with aplastic anemia aged 8~12 years and>12 years was 23%.Conclusion:1.IST was effective in the treatment of acquired aplastic anemia in children.High level bone marrow biopsy hematopoietic area and high level Ret value were effective protective factors for IST.2.The optimal threshold value of ROC curve for bone marrow hematopoietic area evaluation of IST was different in children of different ages,and lower in younger children.