Cognitive Functioning in Vorinostat‐Treated Pediatric and Young Adult Patients Over the First 180 Days After Hematopoietic Stem Cell Transplant

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PURPOSE: Cognitive and psychological difficulties could negatively interfere with treatment adherence and quality of life before and after hematopoietic stem cell transplant (HSCT). Methods to mitigate these changes may have positive effects on treatment success. Prior work has shown that histone deacetylases (HDAC) inhibitors such as vorinostat show promise in reducing the incidence of graft-versus-host disease (GVHD) in allogenic transplant recipients and may mitigate some of the cognitive changes seen following transplant in adults. The current work presents a planned secondary analysis of a phase I/II trial of vorinostat for GVHD prophylaxis (NCT03842696) to establish a cognitive and psychological safety profile for use of this emerging therapeutic in a sample of children, adolescents, and young adults. METHODS: Thirty-two allogeneic transplant recipients (median age = 19) were evaluated with cognitive and health-related quality-of-life (HRQL) measures prior to transplant and at 100 days and 180 days after transplant (N = 25 (cognitive) and 25 (HRQL) at final endpoint). Kolmogorov-Smirnov tests and linear mixed effects modeling were used to compare cognitive performances and HRQL to normative levels and to examine changes over time. RESULTS: Notable cognitive impairments prior to transplant remained relatively stable throughout the first 180 days post-transplant, with no new neurocognitive safety signal over 180 days. Anxiety was apparent at baseline, but behavioral symptoms remained relatively well managed. CONCLUSION: Results highlight cognitive impairments present prior to transplant and support prior findings in an adult population, suggesting that vorinostat does not result in additional cognitive or psychological deficits following transplant.

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