Clinical Significance of Minimal Residual Disease in Risk Stratification and Prognosis of Childhood B-lineage Acute Lymphoblastic Leukemia

Abstract

To explore clinical significance of monitoring the level of minimal residual disease (MRD) at different time point in the risk stratification and prognosis of Childhood B-lineage Acute Lymphoblastic Leukemia. Three hundred and eighty cases of children's B-ALL from Augest 2008 to January 2013 in our hospital were enrolled in this study. MRD levels were detected at day 15, day 33 and week 12 after initial chemotherapy. The event-free survival(EFS) and overall survival (OS) were measured on the basis of MRD levels at different stages of chemotherapy and were compared by Kaplan Meier analyses. The patient's age, initial white blood cell count, chromosome, MLL, BCR/ABL, pretreatment reaction, bone marrow MRD at days 33 were closely related with the 5-year EFS rate. Multiparameter flow cytometry showed the marked MRD and unmarked MRD were not significantly different between their 5-year EFS rate(P>0.05), and the every immune phenotype was also no significantly different between the 5-year EFS rate(P>0.05). The children with MRD≥10-2 at day 15(P<0.01), MRD≥10-3 at day 33 (P<0.01) and MRD≥10-3 on week 12(P<0.01) have a decreased 5-year EFS rate and overall survival, which related with poor prognosis obviously. The 5-year EFS rates at the MRD<10-4(negative), 10-4-10-3, 10-3-10-2 and ≥10-2 at day 33 were 86.6±2.7%, 77.5±4.9%, 70.1±8.0%, and 44.8±9.9%(P<0.01) with significant difference respectively; the 5-year OS rate was 89.5±2.7%, 80±4.9%, 76.0±7.8%, and 53.2±10.1% with statistically significant difference(P<0. 01). The MRD≥10-2 at day 33 is a high risk factor for significant reduction of the 5-year EFS rate and the 5-year OS rate of children with B-ALL. Thus, dynamic monitoring the MRD level can predict relapse of B-ALL after remission.