The contribution of neurocognitive functioning to quality of life after childhood acute lymphoblastic leukemia † Alicia Kunin-Batson 1,3 *, Nina Kadan-Lottick 2 and Joseph P . Neglia 3 1 HealthPartners Institute for Education and Research, Minneapolis, MN, USA 2 Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA 3 University of Minnesota Medical School, Minneapolis, MN, USA *Correspondence to: HealthPartners Institute for Education and Research 8170 33rd Ave S., Mail stop 21111R, Bloomington, MN 55440, USA. E-mail: Alicia.S.KuninBatson@ HealthPartners.com † Statement of prior presentation: Portions presented in abstract form at the 12th International Conference on Long-Term Complications of Treatment of Children and Adolescents with Cancer, Williamsburg, VA, June 2012. Received: 11 July 2013 Revised: 12 November 2013 Accepted: 2 December 2013 Abstract Background: Neurocognitive late effects after childhood acute lymphoblastic leukemia (ALL) are well- documented, but their impact on quality of life (QOL) is not well understood. In this multi-site study, we examined the relative influence of neurocognitive functioning, steroid randomization (prednisone vs. dexamethasone), and demographic characteristics on QOL in first-remission survivors of childhood ALL. Methods: Participants included 263 ALL survivors (ages 7–17 years at the time of evaluation; mean age at diagnosis 3.9 years) who were treated on similar legacy Children’s Cancer Group chemotherapy protocols and did not receive cranial radiation. Children completed detailed neuropsychological perfor- mance tests. The Pediatric QOL Inventory was completed by children and their parents. Participants were a mean of 9 years from diagnosis at the time of assessment (with a range of 4 to 13 years). Results: Children and their parents reported lower mean child psychosocial QOL than healthy population norms (p < 0.05), but were not in the impaired range. Physical QOL was similar to popu- lation norms. Though neurocognitive difficulties were predominantly mild for the sample as a whole, neurocognitive deficits, specifically problems in verbal cognitive abilities and visual-motor integration skills, were significantly associated with poor physical (p < 0.01) and Psychosocial QOL (p < 0.01). QOL was not associated with previous steroid randomization. Conclusions: ALL survivors with neurocognitive deficits are at risk for poor QOL, with broad im- plications for their physical, social, and school functioning. Copyright © 2014 John Wiley & Sons, Ltd. Introduction The success of treatment for acute lymphoblastic leukemia (ALL) in childhood has improved dramatically over the years, resulting in estimated survival rates over 85% for patients treated with current therapies [1]. With this increasing success, more emphasis has been placed on understanding the long-term sequelae of diagnosis and treatment. In addition to well-documented medical late effects of treatment (e.g., osteoporosis, peripheral neurop- athy, and osteonecrosis), childhood ALL survivors are at risk for neurocognitive late effects, including difficulties with attention, visual-motor function, processing speed, and working memory [2,3]. Neurocognitive consequences of ALL therapy with cranial radiation have been shown to negatively impact independent living in adulthood [4], marriage rates, [5] and employment [6]. In ALL patients who do not receive cranial radiation, neurocognitive impairments are comparatively mild. It is not known whether these milder difficulties result in meaningful differences affecting the child’s quality of life (QOL). Quality of life is a multidimensional construct measur- ing subjective well-being. In the context of children with chronic illness, QOL is often measured through parent and patient perceptions of the impact of illness on important functional domains. In children and adults with neurodevelopmental and neurological disorders (e.g., spina bifida, epilepsy, schizophrenia, and coronary artery bypass graft surgery), associations have been found between neuropsychological test scores and patient and parent report of QOL [7–9]. Although a large-scale study in adult survivors of childhood cancer described that treat- ment/diagnosis factors commonly associated with greater degrees of neurocognitive difficulty (i.e., cranial radiation therapy, CNS (central nervous system) tumors, and younger age at diagnosis) are risk factors for poor QOL after treatment [10], other studies that have used neuropsy- chological testing to document degree of neurocognitive difficulty after cancer treatment have not found this association with QOL [11]. Corticosteroid therapy remains an essential component of modern ALL therapy and is most commonly given as either dexamethasone or prednisone. Although studies in non-cancer populations suggest that corticosteroids contribute to cognitive difficulties [12–14], previous stud- ies have shown that the type of steroid regimen used for Copyright © 2014 John Wiley & Sons, Ltd. Psycho-Oncology Psycho-Oncology 23: 692–699 (2014) Published online 4 February 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/pon.3470