A Data‐Driven Redefinition of Early Relapse in Pediatric T Cell Acute Lymphoblastic Leukemia: Evidence for Progression of Disease 15 Months

ABSTRACT Early relapse represents the most adverse prognostic event in pediatric T cell acute lymphoblastic leukemia (T‐ALL). Clinically, early relapse of pediatric T‐ALL is generally defined as relapse occurring within the first 18 months post‐diagnosis, yet its temporal definition has largely relied on clinical convention rather than quantitative evidence. We systematically analyzed relapse dynamics in three independent cohorts: the CHCMU, AALL03B1, and AALL08B1. Hazard functions, cumulative incidence, and time‐dependent hazard ratios were estimated to characterize relapse risk over time. Landmark Kaplan–Meier analyses and univariate logistic regression were performed to evaluate prognostic impact and molecular determinants of relapse. Across all cohorts, the hazard of relapse peaked around the first year after treatment initiation and declined thereafter, whereas cumulative incidence curves plateaued early. Time‐dependent hazard ratios diverged sharply around 10 months and stabilized around 15 months, identifying a high‐risk subgroup. Landmark analyses at 15 months consistently showed that patients relapsing within this window experienced significantly inferior survival compared with those relapsing later or remaining in remission. Univariate logistic regression analysis identified early relapse as significantly associated with recurrent genetic alterations in NOTCH1, PTEN, IL7R, MYC enhancers, and epigenetic regulators. By integrating temporal risk metrics and external validation, this study provides evidence for POD ≤ 15 months as a data‐driven definition of early relapse in pediatric T‐ALL. This threshold captures patients with markedly poor outcomes, is biologically coherent, and provides a clinically actionable framework for risk‐adapted surveillance, therapeutic stratification, and trial design.