Relapse Thresholds (12/24 Mo) Define Survival Disparity in Pediatric B-ALL

This study systematically analyzed relapse patterns in pediatric B-cell acute lymphoblastic leukemia (B-ALL) across 2930 patients from the TARGET and MP2PRT cohorts, with an additional 2972 patients from four independent external validation cohorts, to define clinically relevant prognostic thresholds. Monthly landmark-based Cox analyses identified 13 months as the time point with the peak hazard ratio (HR = 31.97) and 27 months as the time point with the maximum -log10P value (158.08); given the small differences from 12 and 24 months and their greater clinical practicality, POD12 (progression of disease within 12 months) and POD24 (progression of disease within 24 months) were selected as clinically practical landmarks for subsequent analyses. In the TARGET and MP2PRT cohorts, POD12 occurred in 2.56% of patients and POD24 in 8.67%. Patients with POD12 had a 5-year overall survival (OS) of 11.13% versus 90.89% in non-POD12 patients, whereas patients with POD24 had a 5-year OS of 36.19% versus 93.62% in non-POD24 patients. In all four external validation cohorts, POD12 and POD24 were likewise associated with significantly inferior OS compared with their respective non-POD groups. In univariate analyses, E2A-PBX1 and MLL rearrangements were associated with increased risk of POD12 and POD24. These findings support POD12 and POD24 as clinically practical, data-driven landmarks for identifying patients with adverse survival outcomes. They may also inform the exploratory evaluation of 1-year and 2-year progression-free survival as hypothesis-generating candidate early trial endpoints, pending prospective validation.