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

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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.

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Data availability

Data are available from the EpiCenter at Baylor College of Medicine (contact via epicenter@bcm.edu) for researchers who meet the criteria for access to confidential data.

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Funding

This work was supported in part by the National Institutes of Health National Cancer Institute (R01CA1693398, K07CA218362) and the St. Baldrick’s Foundation Consortium Research Grant (522277) Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium.

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Authors and Affiliations

  1. Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, One Baylor Plaza, MS: BCM622, Houston, TX, 77030, USA

    Austin L. Brown, Kimberly P. Raghubar, Olga A. Taylor, Melanie Brooke Bernhardt, Lisa S. Kahalley, Philip J. Lupo, Marilyn J. Hockenberry & Michael E. Scheurer

  2. Duke University, Durham, NC, USA

    Wei Pan

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  1. Austin L. Brown
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  2. Kimberly P. Raghubar
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  5. Lisa S. Kahalley
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  6. Wei Pan
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Contributions

ALB, MJH, and MES designed the study; ALB, OAT, MBB, MJH, PJL, and MES acquired the data; ALB and WP analyzed the data; ALB, KPR, OAT, MBB, LSK, MES interpreted the data; ALB prepared the manuscript; all authors edited and approved the manuscript.

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Correspondence to Austin L. Brown.

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All research procedures involving human participants were in accordance with the ethical standards of the 1964 Helsinki Declaration and were approved by the Institutional Review Board of Baylor College of Medicine.

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Brown, A.L., Raghubar, K.P., Taylor, O.A. et al. Prospective patient-reported symptom profiles associated with pediatric acute lymphoblastic leukemia relapse. Support Care Cancer 29, 2455–2464 (2021). https://doi.org/10.1007/s00520-020-05773-7

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  • DOI: https://doi.org/10.1007/s00520-020-05773-7

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