@article{f51dc6bee85740589fb7cc2a3227617d,
title = "Adaptive functioning and academic achievement in survivors of childhood acute lymphoblastic leukemia: A report from the Children's Oncology Group",
abstract = "Purpose: To characterize academic and adaptive skill outcomes in survivors of high-risk B-lineage acute lymphoblastic leukemia (HR B-ALL). Methods: Participants were 178 patients enrolled on a nontherapeutic clinical trial that aimed to characterize neurocognitive and functional outcomes (ie, academic achievement and adaptive skills) following treatment for childhood HR B-ALL. Eligible patients were treated on Children's Oncology Group AALL0232 clinical trial that included two treatment randomizations: methotrexate delivery (high or escalating dose) and corticosteroid (dexamethasone or prednisone). Academic achievement and adaptive skills were evaluated at one time point, 8-24 months after completing treatment. Results: Multivariable logistic regression showed no significant association between treatment variables and outcomes after accounting for age at diagnosis, sex, and insurance status. In multivariable analyses accounting for sex and insurance status, survivors <10 years old at diagnosis had significantly lower scores in Math (P =.02). In multivariable analyses accounting for sex and age at diagnosis, scores for children with US public health insurance were significantly lower than those with US private or military insurance across all academic and adaptive skills (all P-values ≤.04). Results from univariate analyses showed that boys had significantly lower scores than girls across all adaptive skill domains (all P-values ≤.04). Conclusion: Regardless of treatment randomization, survivors of HR B-ALL <10 years at diagnosis are at risk for deficits in Math and overall adaptive functioning; overall adaptive skills for boys were significantly poorer. Screening and early intervention for patients at highest risk, particularly young patients and lower resourced families, should be prioritized.",
keywords = "academic outcomes, adaptive skills, childhood ALL, neurocognitive",
author = "Jacola, {Lisa M.} and Julie Baran and Noll, {Robert B.} and Willard, {Victoria W.} and Hardy, {Kristina K.} and Leanne Embry and Hullmann, {Stephanie E.} and Larsen, {Eric C.} and Naomi Winick and Kairalla, {John A.}",
note = "Funding Information: Acute lymphoblastic leukemia (ALL), the most commonly diagnosed childhood malignancy, accounts for over one in four new diagnoses of childhood cancer, with very young children (ages 2-4) representing the majority of diagnoses.1 Therapy modifications, such as replacing cranial radiation therapy (CRT) with intensified systemic and intrathecal (IT) chemotherapy for central nervous system (CNS) prophylaxis, have reduced the risk for acute and long-term neurotoxicity without adversely affecting survival.2 However, survivors treated with contemporary chemotherapy approaches are still at risk for deficits in neurocognitive domains including attention and processing speed.3,4 Commonly identified risk factors for poorer neurocognitive outcomes include higher intensity of CNS-directed therapy, younger age at diagnosis, and female sex.3,5,6 Foundational cognitive domains like attention and processing speed are building blocks that support the development of global intelligence7,8 and higher order cognitive abilities.9 In the general population, early onset of attention difficulties predicts increased risk for academic failure and reduced social and functional outcomes throughout the lifespan.10–13 As such, it is reasonable to hypothesize that survivors of childhood ALL, a population with attentional vulnerability, may also struggle with functional outcomes, such as academic achievement and adaptive skills. A better understanding of the early functional implications of neurocognitive deficits is needed to inform strategies for intervention to improve quality of life for survivors. Findings from the limited number of studies of academic achievement in survivors of childhood ALL treated with contemporary therapy are mixed, with some studies reporting performance within age and grade expectations.14,15 Other studies describe lower academic achievement and reduced longer term educational attainment in survivors,16 with young children being at particular risk.5 To date, one study has explicitly examined adaptive skills during therapy in a group of preschool age children diagnosed with standard- or medium-risk ALL.17 Compared to a control group of healthy children matched for age and sex, children with ALL had significantly lower overall adaptive skill development, with particular deficits in conceptual and social domains.This previous study adds to the literature by describing adaptive skills during treatment, but interpretation is limited by the restricted age range of participants (2.5-6 years old), and a lack of information about treatment variables. The American Association on Intellectual and Developmental Disabilities defines adaptive skills as age-appropriate independence in three areas - conceptual (functional academics and communication), practical (self-care, home, and community navigation), and social (social interactions, interpersonal skills). This definition is consistent with the framework of the World Health Organization International Classification of Functioning, Disability, and Health (ICF).18,19 The ICF model is based on a biopsychosocial approach whereby disability is viewed as a multidimensional construct that includes aspects of biology and individual and societal context. Remediation of disability requires a comprehensive understanding of the risk factors and target outcomes, to design effective intervention to improve the fit between the person and the environment.20,21 Accordingly, this study aims to characterize functional outcomes (ie, academic achievement and adaptive skills) and to identify risk factors for poorer outcome in children treated for high-risk B-lineage ALL (HR B-ALL). All patients included in this study were treated on the Children's Oncology Group (COG) protocol AALL0232, which randomly assigned patients with HR B-ALL to receive therapy that included high-dose methotrexate (HDMTX) with leucovorin rescue, or a lower, escalating-dose MTX without leucovorin rescue, plus asparaginase. Patients were also randomly assigned to corticosteroid therapy that included dexamethasone or prednisone. Academic and adaptive skill outcomes were assessed at one time point, 8-24 months postcompletion of treatment. Patients completing the academic and adaptive skill outcomes assessment were between ages 1 and 18 years old at diagnosis. The inclusion of patients that received protocol-directed therapy facilitated examination of clinical variables previously shown to impact neurocognitive outcomes (ie, younger age at diagnosis and treatment variables). Given findings that female sex is a risk factor for poorer neurocognitive outcomes, we also examined the contribution of patient sex to academic and adaptive skill outcomes in this study, hypothesizing that females would demonstrate lower academic achievement and adaptive skills. Finally, we examined whether outcomes differed by socioeconomic status (SES). Consistent with findings from recent studies that documented an association between SES and neurocognitive outcomes in survivors of childhood cancer,22 including a study of neurocognitive outcomes from this cohort,23 we hypothesized that patients with lower SES would have poorer outcomes. Consistent with prior literature, we hypothesized that younger age at diagnosis, female sex, and lower SES would predict lower academic achievement and poorer adaptive skills. Participants were 178 patients enrolled on a nontherapeutic clinical trial that aimed to characterize neurocognitive and functional outcomes (ie, academic achievement and adaptive skills) following treatment for childhood HR B-ALL. Eligible patients were treated on Children's Oncology Group AALL0232 clinical trial that included two treatment randomizations: methotrexate delivery (high or escalating dose) and corticosteroid (dexamethasone or prednisone). Academic achievement and adaptive skills were evaluated at one time point, 8-24 months after completing treatment. Publisher Copyright: {\textcopyright} 2021 Wiley Periodicals LLC",
year = "2021",
month = apr,
doi = "10.1002/pbc.28913",
language = "English (US)",
volume = "68",
journal = "Pediatric Blood and Cancer",
issn = "1545-5009",
publisher = "Wiley-Liss Inc.",
number = "4",
}