Long-term Survival And Follow-up Analysis Of Children's Aplastic Anemia In Single Center

Purpose Hematopoietic stem cell transplantation and combined immunosuppressive therapy are both the main treatments for children with severe and extremely severe aplastic anemia at present,but there are still some controversies about the both methods of treatment under the current situation in our country.Through collecting the data of children's severe aplastic in our center,this study not only analyzed the therapeutic effect of HSCT and IST and the related influencing factors in children with severe aplastic anemia,but also the complications and curative effect of ATG,ALG and HSCT in IST.Methods Retrospective analysis of clinical data including 196 children with SAA or VSAA treated with HSCT or IST was carried out in the Children's Hospital of Suzhou University from February 2009 to November 2017,there were 106 males and 90 females in HSCT group and 106 cases in IST group.According to age,sex,interval time between diagnosis and treatment,and the severity of diseases,the stratified analysis was carried out to compare the overall efficacy(overall survival rate),the effects and complications of HSCT and IST,r-ATG and p-ALG,and the effects of different transplantation methods during HSCT respectively.The survival time was also followed up and the correlation analysis was carried out.Chi-square test was used for intergroup analysis.Kaplan-Meier analysis was used to analyse 5-year overall survival rate and progressive free survival(PFS)of children with different treatment methods.COX proportional risk model was used for multivariate analysis of survival time.P < 0.05 as the difference was statistically significant.Results1.There was no significant difference in age,sex,risk,interval time between diagnosis and treatment,complete blood count in initial visit between HSCT and IST groups.2.5-year overall survival rate(OS)in 196 children was 98.3±1.0%,including that of93.3±4.6% in IST group,and 99.4±0.6% in HSCT group.and the 5-year event-free survival(PFS)was 72.7±3.7%,including that of 69.3±4.2% in IST group,and 93.3±4.6% in HSCT group.According to age,OR was 70.31% in less than 6 years old group and 81.06%(P=0.136)in >6 years old group respectively.According to sex,OR was 80.19% in male group and 74.44%(P=0.436)in female group respectively.According to severity of diseases,OR was 72.82% in SAA group and 82.80%(P=0.048)in vSAA group respectively.According to the interval time of diagnosis and treatment,OR was 82.31% in ?30 days group and 54.88%(P=0.012)in >30 days group respectively.According to complete blood count,OR was 73.47% in PLT?10*10^9/L group and 78.91% in PLT>10*10^9/L group,and PFS was 73.47% in Hb?60 group and 78.91%(P=0.185)in PLT>10*10^9/L group,and OR was 80.73% in ANC?0.5*10^9/L group and 73.111% in ANC>0.5*10^9/L group(P=0.179).According the remission or not after sixth month treatment,OR was 92.14%and 41.111%(P=0.000).3.Through comparison of hemoglobin,platelet and neutrophil absolute count recovery in HSCT group and IST group after 3,6,9 and 12 months,we found that all the p value was <0.05.The OR was 93.33% in HSCT group and 52.41% in IST group(3 months,p=0.002),83.33% vs 69.28%(6 months,p=0.032),86.67% vs 71.08%(9months,p=0.048),and 93.33% vs 71.08%(12 months,p=0.041)in HSCT and IST group respectively.Moreover,OR of HSCT and IST was 78.02% vs 93.33%(p=0.215)in male group in the initial visit,70.67% vs 93.33%(p=0.069)in female group,67.2% vs 81.82%(p=0.470)in the ?6 year group,77.88% vs 100%(p=0.023)in >6 year group,72.54% vs 100%(p=0.515)in SAA group,78.13% vs 93.1%(p=0.132)in vSAA group,77.78% vs 100%(p=0.352)in ?30 days treatment group,and 65% vs 92.31%(p=0.029)in >30days treatment group respectively.And the infection incidence,mainly including sepsis,pulmonary infection,fungal infection,was 60%(18)and 35.92%(58)(p=0.386)in HSCT and IST group respectively.The number of children with herpes virus infection was 7(23.33%)and 5(3.01%)in the two groups(P=0.000).4.5-PFS was 69.6±5.2% in r-ATG group and 69.1±6.8% in p-ALG group(P=0.59)with IST.And OS of the above groups was 73.78% and 62.77% respectively(P=0.083).According to the comparative analysis of complete blood routine,the recovery of leukocytes in r-ATG group was slower than that in p-ALG group in 3,6 and 9 months,and the difference was statistically significant(p=0.012,p=0.015,P=0.043).But there was no significant difference in leukocyte count in 12 months.Furthermore,5-PFS was 73.5±5.4%in ATG 1 group and 49.0±14.8% in ATG2 group(P=0.246).r-AGT and p-ALG were prone to allergic reactions mainly including fever,rash and headache.The number of children with allergic reactions was 52(50.49%)in r-ATG group and 21(33.33%)in p-ALG group(p=0.034).The main adverse reaction after application was sero-disease-like reaction such as fever,rash,headache and Joint swelling and pain,including 64 cases in r-ATG group(62.14%)and 38 cases(60.32%)in p-ALG group(p=0.958).5.5-PFS was 90.9±8.7% in sibling complete coincidence group and 94.7±5.1% in non-sibling complete coincidence group(P=0.67)with HSCT.And 5-PFS was 94.7±5.1%in IST treatment prior to HSCT and 90.9±8.7% in no treatment before HSCT(p=0.70).The incidence of aGVHD was 4(33.33%)and 7(38.89%)children with degree I GVHD in above groups(p=0.826),2(16.67%)and 8(44.44%)children with above degree II GVHD(p=0.023),2(16.67%)and 10(55.56%)children with degree cGVHD in above groups(p=0.004).Moreover,the incidence of GVHD in IST treatment prior to HSCT and in no treatment before HSCT was4(40.00%)and 7(35.00%)children with degree I GVHD in above groups(p=0.848),4(40.00%)and 6(30.00%)children with above degree II GVHD(p=0.187),3(30.00%)and 9(45.00%)children with degree cGVHD in above groups(p=0.192).Conclusion(1)The overall curative effect of HSCT was better than that of IST.Unfortunately.(2)Sex,age,complete blood count in initial visit had no effect on prognosis,but the severity of the disease in the first visit,the interval time between diagnosis and treatment was long,and the nonresponse at the 6th month of treatment were risks for prognosis.Moreover,the hemogram recoverd more quickly in HSCT group than that of IST,but theincidence of infection was the same in both groups.(3)The overall efficacy of r-ATG and p-ALG was comparable,but r-ATG was more prone to allergic reactions.The incidence of serological disease-like reaction after treatment was similar between the two groups.(4)There was no significant correlation between HSCT donor selection,with or without IST before treatment,and the overall curative effect,however,the incidence of degree II or above aGVHD and cGVHD was significantly lower in the sibling group.