PROJECT SUMMARY/ABSTRACT An unprecedented number of older adults with hematological malignancies are receiving hematopoietic cell transplantation (HCT). While previously reserved for younger patients, in the past decade a growing number of older adults have undertaken this intense treatment. Cancer and treatment-related cognitive changes cause distress, hinder resumption of normal routine and roles, and worsen quality of life (QOL). The short and long- term effects of HCT on cognitive function and the extent to which these cognitive changes affect life activities and participation in social roles in older patients are not known. The prevalence and risk of cognitive decline post-HCT are likely greater for older adults because of a greater number of existing health conditions (e.g. vascular disease) and impaired physical and psychologic function pre-HCT that can be exacerbated by treatment and the overall HCT experience. To address this gap, we propose a biopsychosocial cancer and aging framework to measure cognitive function in older adults undergoing HCT. This study will expand on a current pilot cohort study and aims to: 1) examine the profile of cognitive domains affected and the trajectory of cognitive function as measured by neuropsychological testing; 2) identify geriatric assessment factors associated with pre-HCT cognitive impairment and cognitive decline at 100 days, 6 months and 12 months post-HCT; and 3) explore patients’ experiences returning to life activities, participation in social roles and QOL pre-HCT and at 6 months and 12 months post-HCT. This study will enroll 48 additional patients who are: 60 years of age and older, have a hematological malignancy and undergoing an autologous or allogeneic HCT at the Buffett Cancer Center. Patients will complete neurocognitive testing and geriatric assessments at the following time points: pre-HCT and follow-up post-HCT at 100 days, and 6 and 12 months. Patients will participate in semi-structured interviews pre-HCT and on follow up post-HCT at 6 and 12 months. We have assembled a strong interdisciplinary team with clinical and research expertise in geriatrics, geriatric oncology, neuropsychology, and qualitative methods to conduct the proposed study. This research will lay the foundation for a NIH career development award application and for a larger, multi-institutional prospective cohort study to identify factors associated with greater risk for poor cognitive outcomes and help design supportive care interventions that consider the interactions between HCT with aging, existing health conditions and multifactorial geriatric concerns to promote and improve function and QOL for older HCT recipients.