Prognostic significance and risk factors of minimal residual disease ≥1% on 19th day of induction chemotherapy in children with acute lymphoblastic leukemia

Abstract

To assess the prognostic value of minimal residual disease on 19th day of induction chemotherapy (D19 MRD) and the risk factors of D19 MRD ≥ 1% in children with acute lymphoblastic leukemia (ALL) treated following the Chinese Children's Cancer Group ALL protocol. We retrospectively analyzed the data of 243 children with ALL diagnosed between January 1, 2015 and December 31, 2018 in the Department of Pediatrics of Nanfang Hospital (Guangzhou China). Kaplan Meier-survival analysis was performed to compare the survival time between the patients with D19 MRD < 1% and those with D19 MRD ≥ 1%; logistic regression analyisis and Chi-square test were used to identify the risk factors of D19 MRD ≥ 1%. Compared with those with D19 MRD ≥ 1%, the children with D19 MRD < 1% had significantly better 3-year overall survival (100% vs 90.2%, P=0.004) and event-free survival (97.6% vs 71.6%, P < 0.001). Univariate analysis showed that the odds ratio (OR) for mediastinal invasion, T-cell immunophenotype, TEL/AML1 fusion gene and the presence of blasts in peripheral blood on the 5th day were 4.47 (95%CI: 0.275-72.968, P=0.034), 5.250 (95%CI: 1.950-14.133, P=0.02), 0.330 (95%CI: 0.112-0.970, P=0.036) and 4.407 (95%CI: 1.782-10.895, P=0.01), respectively. The initial risk stratification (P < 0.001), white blood cell grades (P=0.018) and its counts (P=0.027), and the number of blasts on the 5th day (P < 0.001) were significantly different between the two groups. Multivariate analysis showed that initial risk stratification as intermediate and high risks (OR=2.889, 95% CI: 1.193-6.996) and the presence of blasts in peripheral blood on the 5th day (OR=4.477, 95% CI: 1.692-11.843) were independent risk factors for poor early treatment response. D19 MRD ≥ 1% is a predictor of poor prognosis in children with ALL. Mediastinal invasion, T-cell immunophenotype and the presence of blasts in peripheral blood on the 5th day are all risk factors for poor early treatment response, while TEL/AML1 fusion gene is a protective factor; the initial risk stratification as intermediate to high risk and the presence of blasts in peripheral blood on the 5th day are independent risk factors for poor early treatment response of the patients.