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.