Long-term Neurocognitive Outcomes in Adult Survivors of Hematopoietic Cell Transplant

Survivors of hematopoietic cell transplant (HCT) are at risk for neurocognitive impairments, which can impact quality of life. Given limited long-term studies, we aimed to characterize the late neurocognitive outcomes in a cohort of adult HCT survivors. Eligible survivors (age ≥21y at time of HCT and alive ³2y followed HCT) completed a 60-question survey of neurocognitive function and quality of life, which included validated self-reported measures such as the NeuroQuality of Life Cognitive Function Short Form (Neuro-QoL) and the Childhood Cancer Survivor Study Neurocognitive Questionnaire (CCSS-NCQ). Analyses of risk factors included univariate comparisons and multivariable logistic regression. Participants (n=1861, 47.7% female, 65.6% allogeneic HCT) were surveyed at a median age of 64.2 years (interquartile range [IQR] 56.8-70.5) at survey and a median 12.0 years (IQR 6.0-21.0) from HCT. Participants reported average Neuro-QoL scores (50.0 in allogeneic HCT survivors and 49.2 in autologous HCT survivors) compared with an expected mean score of 50 in the general population. On the CCSS-NCQ, 17.4-31.2% of participants reported impairments (Z-score >1.28) in task efficiency, memory, emotional regulation, or organization, compared with an expected 10% in the general population (all p<0.01). In multivariable regression analyses adjusted for sex and time since transplant, impaired Neuro-QoL (T-score <40) was independently associated with hearing issues (OR 2.13, 95% CI 1.46-3.10), and sleep impairment (OR 4.41, 95% CI 2.80-6.94) among allogeneic HCT survivors, with comparable values in autologous HCT survivors. In contrast, older age at time of survey was generally associated with a protective effect on cognitive quality of life. In conclusion, long-term adult survivors of HCT reported average cognitive quality of life compared with the general population at a median of 12.0 years following HCT. However, survivors reported persistent impairments in specific neurocognitive domains. Subsets of HCT survivors with certain co-morbid conditions were more likely to report lower quality of life and impaired neurocognitive function. These findings may help providers identify individuals at risk for impairments and facilitate targeted monitoring or potential interventions following HCT.