10069 Background: Childhood cancer survivors experience accelerated aging manifest as physical, cognitive and/or emotional impairments. Aging populations respond to behavioral interventions that address impairment combinations. We aimed to identify and characterize phenotypes (classes) of physical, cognitive and emotional impairments in childhood cancer survivors to inform targets for future intervention. Methods: Factor analysis using St. Jude Lifetime Cohort data (N=4051, 52.2% male, mean [SD] age at diagnosis 8.7 [5.7], assessment 33.9 [10.1] years) generated 9 impairment domains (Table) using 40 items from the Neurocognitive Questionnaire, Brief Symptom Inventory 18 and NHIS Health Status/Limitation of Activities. Latent class analysis estimated impairment patterns and class membership probabilities. Descriptive statistics characterized survivors by class for deficit accumulation index (DAI) score (range 0-1, >0.25 frail), Fried Frailty (FF) score (range 0-5, ≥3 frail), diagnosis and treatment exposures. Logistic regression comparing emotional or cognitive impairment class to the physical impairment class examined associations between survivor characteristics and class membership, adjusting for diagnosis and assessment ages, sex and race/ethnicity. Results: Three classes (phenotypes) differentiated survivors reporting only physical from those reporting both physical and cognitive or emotional impairments. Mean [SD] DAI (cognitive 0.40 [0.10], emotional 0.56 [0.16], physical 0.16 [0.11]) and FF scores (cognitive 1.5 [1.0], emotional 1.8 [1.0], physical 0.9 [0.9]) were highest in the emotional impairment class. Compared to solid tumor survivors (17.1%), brain tumor (33.7%, OR 3.5; 95% CI 2.7-4.4) and leukemia (21.7%, OR 1.5; 95% CI 1.2-1.8) survivors were more likely to be in the cognitive impairment class. Leukemia (OR 1.4; 95% CI 1.1-1.7) and lymphoma (OR 1.4; 95% CI 1.1-1.9) diagnoses increased risk for emotional impairment class membership. Cranial radiation was associated with cognitive (OR 1.8; 95% CI 1.5-2.2) or emotional (OR 1.3; 95% CI 1.1-1.6) impairment class membership. Chest radiation (1.4; 95% CI 1.2-1.7) was associated with emotional impairment class membership. Conclusions: These data provide foundational information for development and testing of targeted behavioral interventions to remediate accelerated aging in survivors. [Table: see text]