Prognostic significance of end‐of‐induction measurable residual disease below 0.01% in pediatric B‐lineage acute lymphoblastic leukemia

Abstract

End‐of‐induction measurable residual disease (EOI‐MRD) predicts poor outcomes in B‐lineage acute lymphoblastic leukemia (B‐ALL). While MRD positivity is conventionally defined at ≥0.01%, data regarding the prognostic relevance of flow cytometry derived EOI‐MRD of <0.01% are emerging. Consecutive pediatric B‐ALL patients diagnosed between January 2018 and December 2022 were analyzed. Overall survival (OS), relapse‐free survival (RFS), and cumulative risk for relapse (CRR) were compared according to undetectable, <0.01%, and ≥0.01% EOI‐MRD status. Of 223 patients, 81 (36%) had detectable EOI‐MRD, including 18 (22.4%) with MRD <0.01%. At 60 months, any detectable EOI‐MRD was associated with higher CRR (44% vs. 22%, p  < 0.001) and inferior OS (57% vs. 83%, p  < 0.001) and RFS (56% vs. 78%, p  < 0.001) compared with undetectable MRD. Outcomes were similar between MRD <0.01% and ≥0.01% groups (CRR 44% vs. 44%, OS 66% vs. 59%, RFS 56% vs. 56%; all p  > 0.05). Compared with undetectable MRD, MRD <0.01% was associated with adverse OS (83% vs. 66%, p  = 0.016) and RFS (78% vs. 56%, p  = 0.029). On multivariate analysis, any level of detectable EOI‐MRD independently predicted adverse outcomes (HR: 2.22, 95% CI: 1.30–3.8; p  = 0.004 for OS and HR: 2.38, 95% CI: 1.42–3.98; p  = 0.001 for RFS) [CI: confidence interval and HR: hazard ratio]. EOI‐MRD <0.01% is associated with inferior outcomes. Whether treatment intensification based on EOI‐MRD <0.01% improves outcomes requires prospective evaluation.