Introduction
Hematopoietic cell transplant (HCT) is increasingly performed as a potentially curative treatment for both malignant and non-malignant disorders. However, survivors are at higher risk for developing chronic health conditions, which contributes to increased morbidity and mortality compared with non-HCT cancer survivors and the general population.1,2 Neurocognitive function is a broad category which encompasses memory, attention, concentration, planning, organization, and problem solving, among other abilities. Impairments in cognition can complicate the post-HCT course with substantial effects on both specific cognitive abilities as well as overall quality of life.3 Survivors of pediatric HCT are at greater risk for neurocognitive toxicity due to treatment exposures during a developmentally vulnerable period. Despite this fact, few studies have described the late neurocognitive outcomes in pediatric HCT survivors.
In studies of pediatric cancer survivors regardless of transplant history, long-term survivors reported greater neurocognitive impairments at an average of 2 decades following diagnosis compared with healthy siblings,4,5 with more impairments noted in survivors of central nervous system (CNS) tumors and acute lymphoblastic leukemia (ALL) following direct CNS treatment or prophylaxis.6,7 In these patients, survivors with neurocognitive deficits were less likely to attain educational milestones8 or follow recommendations for general care.9 Therefore, further studies of long-term neurocognitive function are needed specifically in pediatric HCT survivors to identify potential areas for intervention with the goal of improving patient function and quality of life.
Despite known or suspected risk factors, neurocognitive dysfunction may not become apparent until decades after HCT. The existing literature is limited by inconsistent definitions, heterogeneous testing methods, and short follow-up time.3,10-13 Specifically among pediatric HCT survivors, there is a particular lack of data describing neurocognitive outcomes and functional impact beyond 5 years post-HCT.14 Overall, the limited understanding of the incidence and characterization of neurocognitive dysfunction following HCT has been recognized as an important area deserving of further research.15,16 In this study, we aim to address this gap in knowledge by characterizing the late neurocognitive outcomes in a cohort of long-term pediatric HCT survivors. We also examine the association between treatment variables and medical co-morbidities and neurocognitive dysfunction in this patient population.