Prospective patient-reported symptom profiles associated with pediatric acute lymphoblastic leukemia relapse

Despite improvements in frontline pediatric acute lymphoblastic leukemia (ALL) treatment, relapse remains a concern. Research in adult cancer patients suggests that patient-reported symptoms may predict survival, but the relationship between symptoms and relapse for pediatric ALL has received little attention. Pediatric patients with ALL (age 2–18 years) and/or their primary caregivers completed symptom surveys at the end of induction, start of delayed intensification (DI), start of maintenance cycle 1 (MC1), and start of maintenance cycle 2 (MC2). Symptom clusters for co-occurring fatigue, pain, sleep disruptions, and nausea were defined using latent profile analysis. Hazard ratios (HR) and 95% confidence intervals (CI) for the association between symptom clusters, individual symptoms, and subsequent relapse were calculated using multivariable Cox proportional hazards models, adjusting for clinical and demographic factors. Eligible patients (n = 208) were followed an average of 2.6 years for the incidence of relapse (n = 22). Associations between relapse and symptoms were identified for fatigue at DI (HR = 1.83, 95%CI 1.23–2.73) and MC1 (HR = 2.14, 95%CI 1.62–2.84), pain at DI (HR = 1.80, 95%CI 1.19–2.72), nausea at the end of induction (HR = 1.19, 95%CI 1.01–1.39), and sleep disturbances at the end of induction (HR = 2.00, 95%CI 1.11–3.62), DI (HR = 1.73, 95%CI 1.01–2.96), and MC1 (HR = 2.19, 95%CI 1.10–4.35). Symptom clusters comprised of individuals with a higher average symptom burden at DI were significantly (p < 0.05) associated with relapse. Patient-reported symptoms may provide prognostic information to aid in the identification of pediatric ALL patients at increased risk of relapse.