Optimal threshold selection in the UKALL14 cohort. To determine the optimal EWALL-PI threshold for defining risk groups, we assessed 14 selected thresholds using a cohort of 79 patients treated on UKALL14 with chemotherapy only. The cumulative incidence of relapse (CIR [A]) and OS rates (B) were calculated for patients above (red) and below (blue) each threshold. (C-D) show the proportion of patients with EWALL-PI scores above (red) and below (blue) each of the selected EWALL-PI thresholds. Threshold analysis was performed by sorting the PI, dividing the cohort into bins comprising ∼5 cases (∼6% cohort) and sequentially testing each threshold until the exemplar clinical criteria were met. The most discriminatory threshold (ie, the one with the maximum difference between CIR and OS rates) was 2.50, which divided the chemotherapy cohort 75%/25% but the whole UKALL14 cohort 52%/48%. Patients with a EWALL-PI score <2.50 had a CIR at 3 years of 15% vs 35% for patients with a score ≥2.50 (P < .001). The equivalent OS rates at 3 years were 90% vs 59% (P < .001).