Prognostic and therapeutic implications of measurable residual disease levels during remission induction of childhood ALL

• Treatment intensification in patients with B-ALL with MRD ≥1% at day 19 of remission induction significantly enhances EFS.

• Among patients with negative day 46 MRD, those who also had negative MRD at day 19 have particularly favorable treatment outcomes.

We evaluated the prognostic and therapeutic significance of measurable residual disease (MRD) during remission induction in pediatric patients with acute lymphoblastic leukemia (ALL). In the Chinese Children Cancer Group ALL 2015 protocol, 7640 patients were categorized into low-, intermediate-, or high-risk groups based on clinical and genetic features. Final risk classification was determined by assessing MRD using flow cytometry on days 19 and 46 of remission induction with additional intensified chemotherapy for day 19 MRD ≥1%. Patients with B-ALL with negative MRD (<0.01%) on day 19 or day 46 had significantly better 5-year event-free survival (EFS) than those with MRD of between 0.01% and 0.99% who, in turn, had better EFS than patients with MRD of ≥1%. Provisional low-risk patients with day 19 MRD ≥1% but negative day 46 MRD who were reclassified as intermediate risk had a 5-year EFS that was comparable with that of low-risk patients with day 19 MRD of 0.3% to 0.99% and negative day 46 MRD (82.5% vs 83.0%) and better EFS than provisional low-risk patients with MRD on both days (83.0% vs 72.6%; P < .001). Similarly, patients with provisional intermediate-risk B-ALL with day 19 MRD ≥1% but negative day 46 MRD who received additional therapy had better 5-year EFS than those with day 19 MRD between 0.3% and 0.99% (70.7% vs 53.0%; P < .001). Among low-risk patients with negative day 46 MRD, those with negative day 19 MRD had superior EFS than those with positive day 19 MRD (91.7% vs 86.1%; P < .001). Optimal use of day 19 MRD could improve individualized treatment and outcomes. This trial was registered at www.chictr.org.cn as #ChiCTR-IPR-14005706.