Analysis Of Prognostic Factors Of Pediatric Acute Lymphoblastic Leukemia Treated With CCLG-2008-ALL Protocol

Background and objective:Pediatric acute lymphoblastic leukemia(ALL)is a curable disease whose overall survival is over 80%.The overall survival of ALL can be affected by treatment failure.CCLG-2008-ALL protocol is a widely applied multi-center collaborative program carried out in China between 2008 and 2012.In this study,we analyzed the factors related to treatment failure,which might shed light on improving future protocols.Method:This study included all the ALL patients(diagnosed according to MICM)treated with CCLG-2008-ALL protocol in our hospital from March 1,2008 to December 31,2012.The clinical data was collected from the medical record data reporting system.The treatment failure includes relapse,death,and the secondary tumor.The counting data was represented by number(%).Chi-square test or Fisher exact test was used for comparison between groups.The survival state(such as OS,EFS,RFS,TFS)was calculated by K-M curve,whereas prognostic factors were analyzed by COX regression model.The follow-up time ended in October 31,2019.Results:400 patients diagnosed with ALL were enrolled,which included 238 males and 162 females(male to female ratio 1.47:1),and the median age was 55 months(4?178 months).The median follow-up time was 102 months(2?136 months).The number of treatment failure was 152 which accounted for 38%of all patients.There were 30 non-relapse deaths(taking up 19.7%of treatment failure),including 7(4 and 3 patients died of infection and bleeding,respectively)treatment-related death(occupying 23.3%of non-relapse deaths,4.6%of treatment failure),8 non-remission death(accounting for 26.7%of non-relapse deaths,5.3%of treatment failure),and 15 died due to financial burden(accounting for 50%of non-relapse deaths,9.9%of treatment failure).During the follow-up period on a regular basis,122 children suffered from relapse(accounting for 80.3%of treatment failure).Among the relapse patients,61 died after giving up the treatment(accounting for 50%of relapse patients),10 died of infection during re-induction therapy,5 died due to non-remission after treatment,7 died of transplant-related complications,and 6 died from unknown causes.37 patients recurred in the very early stage,which took up 30%,whereas other 38(31%)and 47(39%)patients recurred in the early stage and late stage,respectively.There were 107 cases of marrow relapse which claimed 82 death(76.6%),4 marrow plus central nervous system(CNS)relapse claimed 3 death(75%),5 relapsed in bone marrow plus testis and 1 patient died(20%),3 testicular relapse caused no death,whereas the 3 CNS relapse contributed to a 100%death rate.20 cases lost contact during the follow-up.No secondary tumors were found during the follow-up.The overall OS rates in 3,5,7,and 10 years were(77.6±2.1)%,(72.9±2.3)%,(69.7±2.3)%,and(69.4±2.3)%,respectively.The event-free survival(EFS)rates of 3-,5-,7-,and 10-year were(71.6±2.3)%,(63.7±2.4)%,(61.1±2.5)%,and(59.2±2.6)%,respectively.The relapse-free survival(RFS)rate of 3-,5-,7-,and 10-year were(78.8±2.1)%,(70.6±2.4)%,(67.8±2.5)%,and(65.0±2.7)%,respectively.There were significant differences in OS,EFS,RFS among different risk groups,and the high-risk group persisted the worst outcome.The multivariate analysis suggested that white blood cell(WBC)count,immunophenotype,and the 12-week MRD level were risk prognostic factors for relapse-free survival in children with ALL.The univariate analysis indicated that several factors were significantly related to the poor TFS,including age?10 years,the high risk rank in the risk grade,initial WBC count>100×109/L,fusion genes with BCR-ABL1 positive,insensitive to prednisone response(PPR),and the early response to treatment(D15 blast>25%,D33 blast?5%,D33 MRD>1×10-2,and W12 MRD>1×10-3).Multivariate analysis showed that age,WBC,D15 bone marrow blast,and the 12-week MRD level were risk prognostic factors for treatment-failure survival in children with ALL.Conclusion:(1)There were significant differences in OS,EFS,RFS among different risk groups,and the high-risk group persisted the worst outcome.(2)Relapse was the most common cause of treatment failure in childhood ALL.The WBC count at diagnostic stage,immunophenotype,and the MRD level at twelfth week were the independent prognostic factors for RFS.(3)Infection was the main cause of the treatment-related death.Financial difficulties occupied a large proportion of non-relapse death.(4)Age,WBC at diagnostic stage,D15 bone marrow blast,and the MRD level at twelfth week were the independent prognostic factors for TFS.