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

Abstract

We evaluated the prognostic and therapeutic significance of measurable residual disease (MRD) during remission induction in pediatric acute lymphoblastic leukemia (ALL) patients. In the CCCG-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 MRD assessed via flow cytometry on Days 19 and 46 of remission induction, with additional intensified chemotherapy for Day 19 MRD ≥1%. B-ALL patients with negative MRD (<0.01%) on Day 19 or Day 46 had significantly better 5-year event-free survival (EFS) than those with MRD 0.01-0.99%, who in turn had better EFS than patients with MRD ≥1%. Provisional low-risk patients with Day 19 MRD ≥1% but negative Day 46 MRD, reclassified as intermediate-risk, had comparable 5-year EFS to low-risk patients with Day 19 MRD 0.3-0.99% 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<0.001). Similarly, provisional intermediate-risk B-ALL patients with Day 19 MRD ≥1% but negative Day 46 MRD, who received additional therapy, had better 5-year EFS compared to those with Day 19 MRD between 0.3-0.99% (70.7% vs. 53.0%, P<0.001). Among low-risk patients with negative Day 46 MRD, those with negative Day 19 MRD had superior EFS compared to those with positive Day 19 MRD (91.7% vs. 86.1%, P<0.001). Optimal use of Day 19 MRD could improve individualized treatment and outcomes. Chinese Clinical Trial Registry (ChiCTR-IPR-14005706).