Prognostic Value of Minimal Residual Disease in Children with Acute Lymphoblastic Leukemia.

Purpose To assess the prognostic value of determination of minimal residual disease in the bone marrow after multiagent remission induction therapy in children with acute lymphoblastic leukemia. Methods From September 2001 to December 2004, 102 patients with newly diagnosed B-cell precursor acute lymphoblastic leukemia were enrolled on protocol ALL-XH-99. Minimal residual disease in the bone marrow at the end of remission induction therapy, before high-dose methotrexate, early intensification as well as 1 year, 2 year of maintains therapy was detected by multi-parameter flow cytometry with various combinations of monoclonal antibodies for leukemia-associated immunophenotype. The probability of event-free survival was estimated by Kaplan-Meier analysis and the distributions of probability of event-free survival (pEFS) were compared using the log-rank test. Chi-square analysis or Fisher exact test were used to compare differences in the distribution of biologic presenting features. A Cox proportional hazards model was used to identify independent prognostic factors. Results [circ1] The probability of 39-month event-free survival (EFS) was significantly worse for patients who achieved a minimal residual level ≥ 0.01% in the bone marrow on the remission date as compared to that of other patients with a minimal residual level < 0.01% (0.00% vs 83.00±9.90%, P=0.0000). [circ2]Univariate analysis indicated that there were no relationship between level of minimal residual disease at the date of complete remission and biologic presenting features (gender, age, white blood cells), but did Philadelphia chromosome, ALL-XH-99 risk groups as well as lymphoblasts in the bone marrow on day 19 (P<0.05). [circ3] Multivariate analysis suggests patients with high level minimal residual disease after the first induction course was an independent prognostic factor (hazard ratio, 5.381; 95% confidence interval 0.004 to 0.624; P=0.020). Conclusions Early treatment response as assessed by minimal residual leukemia determination by flow cytometry has important prognostic significance and can be performed in a resource-poor patient population. Patients with level of minimal residual disease ≥ 0.01% at end of remission induction ought to be used an novel and more intentive chemotherapy.