Project Description Narrative:
Among childhood cancer survivors, those that receive allogeneic hematopoietic cell transplantation (HCT) are at high risk for developing late medical conditions. Despite their therapeutic utility, radiation and chemotherapy exposure drives DNA damage, oxidative stress, and inflammation. As a result, neurocognitive impairment is a significant complication that often persists years after transplant, which has not been systematically addressed in this high-risk population. Small studies (including this research team's own preliminary data) done in non-HCT cancer survivors treated with chemotherapy have suggested that attention, working memory, and processing speed are selectively impaired in this population. This suggests the presence of abnormalities in brain networks mediating these cognitive domains.
This study will use behavioral and neuroimaging methods to assess neurocognitive decline associated with HCT. The researchers hypothesize that pediatric, adolescent, and young adult HCT patients for hematologic malignancies will experience neurocognitive decline directly after HCT that will persist years after transplantation.
The research team will use a unique combined prospective and retrospective observational study that will enroll patients (age eight to 26) with hematologic malignancies receiving their first allogeneic HCT at Children's Wisconsin to study longitudinal changes in cognition and neural mechanisms. They will also enroll a cohort of patients three or more years post-HCT to study the persistence of this cognitive dysfunction.
By establishing whether deficits in cognitive/neural function in this population can be detected early and with high sensitivity and specificity, results from this study have the potential to mitigate the treatment of HCT-related cognitive decline through adoption of either earlier intervention or auxiliary treatments and could change the future conditioning regimens and supportive care offered to these patients. These findings have the potential to impact the course of survivorship care for patients across the state of Wisconsin and beyond.