Clinical significance of minimal residual disease in young adults with standard-risk/Ph-negative precursor B-acute lymphoblastic leukemia: results of prospective study

Clinical risk classification is inaccurate in predicting outcome in adult patients with acute lymphoblastic leukemia (ALL), sometimes resulting in patients receiving inappropriate chemotherapy or stem cell transplantation. To identify complementary markers suitable for further treatment stratification in patients with standard-risk (SR)/philadelphia-negative (Ph-negative) precursor B-ALL, we evaluated the predictive value of minimal residual disease (MRD) after induction and consolidation chemotherapy in strictly defined SR/Ph-negative precursor B-ALL patients who were treated with a standard protocol using quantitative real-time polymerase chain reaction with the rearranged immunoglobulin heavy chain gene as a molecular marker. The cytologic complete response (CR) rate was 92.3 % after induction. At this time point, the molecular CR rate was 73.9 %. Patients with molecular CR (MolCR) after induction had a significantly higher probability of disease-free survival (DFS; 78.8 vs 30.8 %; P = .001) and of overall survival (OS; 82.4 vs 41.7 %; P < .0001) compared to patients with molecular failure (MolFail). MRD at end consolidation had the same significance. Quantitative MRD assessment identified patients with MolFail after induction and/or consolidation as a high-risk group, with 3-year DFS and OS rates of 28.6 and 35.7 %, respectively. Patients with MolCR after induction and consolidation were classified as low-risk and had 3-year DFS rate of 89.7 % and OS rate of 93.3 %. Thus, MRD quantification during treatment identified prognostic subgroups within the otherwise homogeneous SR/Ph-negative precursor B-ALL population who may benefit from individualized treatment.