Pre-Hematopoietic Cell Transplantation (HCT) Frailty Is Associated with Lower Cognitive Function and Health-Related Quality of Life (HRQOL) in Older Adults Undergoing HCT

Background: Increasing numbers of older adults are undergoing HCT. Pre-HCT frailty is predictive of survival in older adults.¹ However, an association between frailty and functional outcomes and HRQOL are unknown in older adults undergoing HCT. Examining potential associations is important to identify higher-risk HCT candidates who will benefit from proactive interventions and help patients and clinicians with treatment decision making. The objective of this study is to examine the association of pre-HCT frailty status with cognitive function and HRQOL at 12-months post-HCT in adults ≥ 60 years undergoing HCT.

Methods: This study is a secondary data analysis of a longitudinal cohort study at a single center conducted between 2018-2022, that included adults ≥60 years who have a diagnosis of a hematologic malignancy undergoing HCT. Participants completed the Fried Frailty assessment, the Montreal Cognitive Assessment (MoCA), and the European Quality of Life Questionnaire--Cancer 30 (QLQ-C30) prior to admission for HCT and at 12-months post-HCT. Frailty was defined as possessing three or more of the following: unintentional weight loss, low grip strength, self-reported exhaustion, slow gait speed, and low physical activity.² Pre-frail was defined as having 1-2 of the criteria. Multinominal modeling with a random effect for subject was used to account for the correlation within patient, and to compare frailty status over time. ANOVA was used to compare 12-month post-HCT cognitive function and HRQOL between pre-HCT frailty statuses, and pair-wise comparisons were adjusted using Tukey’s method. All analyses were done in SAS 9.4 and p <0.05 was considered statistically significant.

Results: 104 older adults completed pre-HCT assessment. The average age at HCT was 67.7 years (range: 60.2-76.6). There were 69 (66.3%) allogeneic and 35 (33.7%) autologous HCT recipients. Pre-HCT, 10.6% were frail, 63.5% were pre-frail, and 26% were non-frail. At 12-months post-HCT (n=62), the prevalence of frail, pre-frail and non-frail were 25.8%, 67.7% and 6.5% respectively. There was a statistically significant increase in the prevalence of frailty between pre-HCT and 12 months post-HCT (odds ratio= 4.9, p= <0.001). Pre-HCT frailty status was associated with a lower 12-month MoCA score, and lower physical and emotional functioning on the QLQ-C30. The mean 12-month MoCA score for those who were frail pre-HCT was 23.4 compared to 26.2 and 25.4 for those who were pre-frail and non-frail, respectively (p=0.033). The mean score for the physical function sub-score on the QLQ-C30 at 12-month was 68.3 for patients who were frail pre-HCT compared to 83.9 and 83.2 for those who were pre-frail and non-frail, respectively (p=0.034). The mean score for the emotional function sub-score on the QLQ-C30 at 12-month was 76.1 for patients who were frail pre-HCT compared to 90.6 and 87.9 for those who were pre-frail and non-frail, respectively (p=0.034).

Conclusions: Pre-HCT frailty is associated with lower cognitive performance and HRQOL at 12-months post-HCT, specifically physical and emotional functioning. At one year, the prevalence of frailty in HCT survivors approaches that of community dwelling older adults ≥ 80 years.³ The increased prevalence reflects the stress of cancer, accumulation of high-intensity therapeutic exposures, and transplant related morbidities. This study highlights the need to provide targeted interventions to mitigate and prevent frailty pre-HCT and early in the recovery process to preserve cognitive function and maximize HRQOL for older adults post-HCT.

1.Sung, A. D., Koll, T., Gier, S. H., Racioppi, A., White, G., Lew, M., ... & McCurdy, S. R. (2024). Preconditioning frailty phenotype influences survival and relapse for older allogeneic transplantation recipients. Transplantation and Cellular Therapy, 30(4), 415-e1.

2.Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. PMID: 11253156.

3.Collard RM, Boter H, Schoevers RA, Oude Voshaar RC. Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc. 2012 Aug;60(8):1487-92. PMID: 22881367.