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Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for many hematologic conditions. Despite advances in conditioning and supportive measures, however, there remain significant comorbidities that threaten survivorship. Adverse effects of stress-related biobehavioral processes—defined here as the interactions of behavioral, psychological, and socioenvironmental factors with biology—impact immune recovery and function and are particularly salient in the HCT context, given the importance of immune reconstitution for improved survivorship. However, biobehavioral processes have been underinvestigated in this vulnerable group compared with other cancer populations. Here the Biobehavioral Research Special Interest Group (SIG) of the American Society for Transplantation and Cellular Therapy provides an expert review to inform research directions explicating the biological correlates of behavioral symptoms and evaluate the impact of these on HCT outcomes. The goal of this expert review is to provide a foundation for advancing science that effectively integrates behavioral and biological processes to optimize quality of life and improve clinical outcomes for HCT recipients.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy can lead to durable responses in patients with relapsed/refractory hematologic malignancies. Immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) are common and may place patients at risk for longer-term cognitive impairment. OBJECTIVE: This study examined changes in cognition in the first year after CD19-directed CAR-T-cell therapy for lymphoma, as well as CAR T-cell therapy-specific risk-factors (e.g., ICANS, CRS) and non-specific risk factors (e.g., baseline quality of life, frailty) for worsening cognition. STUDY DESIGN: Patients’ perceived cognition was assessed at baseline and at days 90 and 360. Clinical variables were abstracted from medical records. Piecewise mixed models were used to examine acute change (i.e., within 90 days) and longer-term change (i.e., from 90 days to 360 days) in cognition as well as to explore risk factors for worsening cognition. RESULTS: Among 118 participants (mean age 61, 59% male), mean levels of perceived cognition did not change from baseline to day 90 (p values>0.05) but worsened from day 90 to day 360 in global cognition and in the domains of memory, language, organization, and divided attention (p values0.05). Other putative risk factors were not associated with acute or longer-term changes in perceived cognition (p values>0.05). CONCLUSIONS: CAR T-cell therapy recipients reported delayed deterioration in several cognitive domains, although changes were small. These findings may be useful when educating future patients on what to expect when receiving CAR T-cell therapy.