Prospective patient-reported symptom profiles associated with pediatric acute lymphoblastic leukemia relapse
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ORIGINAL ARTICLE
Prospective patient-reported symptom profiles associated with pediatric acute lymphoblastic leukemia relapse Austin L. Brown 1 & Kimberly P. Raghubar 1 & Olga A. Taylor 1 & Melanie Brooke Bernhardt 1 & Lisa S. Kahalley 1 & Wei Pan 2 & Philip J. Lupo 1 & Marilyn J. Hockenberry 1 & Michael E. Scheurer 1 Received: 13 May 2020 / Accepted: 10 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose 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. Methods 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. Results 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. Conclusion Patient-reported symptoms may provide prognostic information to aid in the identification of pediatric ALL patients at increased risk of relapse. Keywords Sleep . Fatigue . Pain . Nausea . Pediatric acute lymphoblastic leukemia . Relapse
Introduction Acute lymphoblastic leukemia (ALL) is the most frequent malignancy diagnosed in children in the USA [1]. Due to Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00520-020-05773-7) contains supplementary material, which is available to authorized users. * Austin L. Brown [email protected] 1
Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, One Baylor Plaza, MS: BCM622, Houston, TX 77030, USA
2
Duke University, Durham, NC, USA
the improvements in the treatment of pediatric ALL over the past several decades, 5-year survival rates now exceed 90% in most developed countries [2]. However, approximately 20% of cases experience relapse [3]. Unlike survival rates for newly diag
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