MRD ≥0.01% Before or Day 100 Post-HSCT Flags Higher Relapse Risk in Pediatric ALL

Measurable residual disease (MRD) ≥0.01% identified a substantially higher-risk group among 1,014 children and young adults (ages 4–21) receiving matched-donor allogeneic HSCT in the extended international FORUM cohort (NCT01949129); 21% were MRD-positive before transplant. Pre-HSCT MRD-positive patients had lower 3-year EFS (59% vs 73%; p<0.001) and higher 3-year cumulative relapse (33% vs 20%; p<0.001), while further separating MRD-positive patients at <0.1% vs ≥0.1% did not improve risk stratification and no adverse pre-HSCT MRD signal was demonstrated in T-ALL. MRD at day 100 was even more discriminating: MRD-positive patients had 3-year EFS of 47% vs 77% and relapse of 51% vs 17% (both p<0.001); importantly, MRD positivity did not inevitably lead to relapse. This sits on top of FORUM’s established conditioning benchmark, where TBI/etoposide produced 2-year OS of 91% and relapse of 12% versus 75% and 33%, respectively, with chemotherapy-only conditioning.