Analysis Of Biological Characteristics, Early Response To Treatment And Access Their Effect On Prognosis In Children With Acute Lymphoblastic Leukemia

Objective: This study is aimed to explore the biological characteristics and early treatment outcome of childhood acute lymphoblastic leukemia(ALL) and assess their effect on the prognosis. Through this study, we try to provide a theoretical evidence to the more scientific stratification treatment and further improve the event free survival(EFS) of childhood ALL.Methods: Clinical data were collected in pediatric patients with newly diagnosed ALL from January 1, 2010 to December 31, 2014 in department of pediatric hematology, Fujian Medical University Union Hospital. A total of 348 patients were enrolled. We analyzed retrospectively the biological features and early treatment response of the 348 cases of childhood ALL, and assessed overall survival rate(OS)and event free survival(EFS). SPSS19.0 statistical software was chose to analyze all the data. We used the Kaplan-Meier method to calculate 5-year OS and EFS, and LogRank test was applied to compare survival curves. Univariate analysis was used to analyze respectively several prognostic factors, such as sex, age at diagnosis, initial WBC, immunophenotype, TEL/AML1 fusion, E2A/PBX1 fusion, BCR/ABL1 fusion,response to prednisone, prolymphocyte percent in bone marrow(BM) on the 15 th day,minimal residual disease(MRD) on the 33 th day in induction treatment. Some effective prognostic factors were screened, and then we establish the multivariate COX regression model to do the analysis of multiple factors.Results:1. 348 children with ALL were enrolled, and sex ratio was 1.34:1(199/149). The mean age was 4 years(ranged 11 months to 14 years). The percentage of the patient with B-cell phenotype reached 93.4%. 151 patients with childhood ALL harbored a recurrent chromosomel alteration. Of all the fusion genes detected, TEL/AML1 fusion was the most common, and its ratio reached 19.59%. The percentage of the patients with hyperdiploid was 14.57%, which was the most common abnormal chromosome.According to the risk stratification, we divided 157 cases(45.11%) into low-risk(LR)group, and 102 cases(29.31%) into intermediate-risk(IR) group, and 89 cases(25.58%) into high-risk(HR) group.2. 94.83% patients showed a good response to prednisone. The rate of complete remission was 97.99%. 47 cases were died, and the total mortality rate was 13.50%.22 cases(6.32%) died from chemotherapy. The mortality rate related to chemotherapy of LR group was 3.82%, and 2.94% of IR group, while 14.61% of HR group. Different risk group had the different rates mortality rate related to chemotherapy(P=0.001),and HR group was the highest. Total incidence of relapse was 9.2%, and the mean time of relapse was 15.6 months(ranged 2.6months to 43.9 months). Of 32 cases who had relapsed, 25 cases were died, and the rate associate with relapse was 7.18%. The mortality rate related to relapse of LR group was 3.18%, and 4.90% of IR group, while 16.85% of HR group. Different risk group had the significantly different mortality rate related to relapse(P=0.000),and HR group was the highest. The total 5-years OS was(83.2±2.5)%, and 5-years EFS was(81.4±2.5)%. 5-years OS in LR group was(91.6±2.5)%, and(82.9±7.7)%of in IR group, and(64.8±5.5)% of HR group. 5-years EFS in LR group was(89.7±2.7)%, and(81.9±2.5)% of IR group, and(62.9±5.9)% of HR group.Childhood ALL belonged to different risk groups had significant difference of survival rates(P<0.000).3. The result of univariate analysis showed that sex, age and E2A/PBX1 fusion had no significant influence on OS or EFS, while other factors could affect prognosis,including initial WBC(P=0.000), immunophenotype(P=0.000), TEL/AML1fusion(P=0.002), BCR/ABL1 fusion(P=0.006), response to prednisone(P=0.000),prolymphocyte percent in bone marrow(BM) on the 15thday(P=0.019), and minimal residual disease(MRD) on the 33 th day in induction treatment(P=0.034). The result of the COX regression multivariate analysis showed that initial WBC?50×109/L(P=0.000),T-cell phenotype(P=0.006), and poor response to prednisone(P=0.029)were effective prognostic factors for cases with childhood ALL.Conclusions:1. The prognosis of childhood ALL was favorable, and 5-years OS and EFS approximate to 80%.2. The higher risk group children with ALL belong to, the lower OS and EFS they have. The prognosis of HR group of childhood ALL remains to be improved.3. Initial WBC?50×109/L, T-cell phenotype, and poor response to prednisone have important prognostic values in childhood ALL, and could be used as important basis for risk stratification protocol.