PREPARE ALL: An Artificial Intelligence Tool for Predicting Relapse in Children With Acute Lymphoblastic Leukemia

PURPOSE: The Pediatric Relapse Prediction and Risk Evaluation for Acute Lymphoblastic Leukemia (PREPARE-ALL) tool aims to predict relapse in pediatric ALL by integrating clinical expertise with artificial intelligence and machine learning (ML), particularly Extreme Gradient Boosting (XGBoost). PREPARE-ALL demonstrates that multicenter, protocol-driven clinical and laboratory data can be used through ML to generate reproducible relapse predictions with greater sensitivity than individual clinician assessments. METHODS: PREPARE-ALL was developed using data from the ICiCLe ALL-14 pretrial cohort across five centers, incorporating 33 clinical and laboratory features. RESULTS: Among 2,252 patients enrolled in the study, 565 (25.1%) relapsed. Using an 80:20 train-test split, XGBoost achieved a sensitivity of 68.5% (245/447 relapses detected). Additional metrics included a positive predictive value of 31.3%, a negative predictive value of 82.8%, an accuracy of 54.8%, and a specificity of 50.3%. Key predictors of relapse included high hyperdiploidy and BCR-ABL1 fusion positive, positive measurable residual disease status at the end of induction, sex, age, highest presenting WBC, and final risk group. Three clinicians scored the validation data set; the developed model achieved a higher recall (68.5%) compared with clinical judgment (approximately 31%-36%). CONCLUSION: PREPARE-ALL identifies twice as many relapses as clinicians and serves as a practical decision-support tool for early relapse triage and treatment planning, enabling timely therapeutic adjustments and improved outcomes in pediatric ALL.