Older Survivors of Allogeneic Hematopoietic Cell Transplantation (HCT) with Chronic Graft Vs. Host Disease (cGvHD) Demonstrate Higher Risk of Frailty As Compared with Autologous HCT Recipients: A Report from the Bone Marrow Transplant Survivor Study-2

Background: Approximately 10% of older (≥65y) individuals in the general population demonstrate frailty (Collard RM et al. J Am Geriatr Soc. 2012;60:1487-92). HCT recipients are at risk for accelerated aging, given the high-intensity therapeutic exposures and excessive burden of morbidity after HCT.  We examined the prevalence and predictors of frailty in elderly (≥65y) HCT survivors.

Methods: Participants included 276 older HCT survivors (median age at study participation: 70 y (65-84), who had undergone HCT (allogeneic: n= 83, autologous: n=196) between 1985-2010. Median time from HCT was 8.9y (3.7-29.1). Following well established survey-based screening tools for frailty (Pialoux T et al. Geriatr Gerontol Int. 2012;12:189-97), all participants completed a self-report survey that included questions pertaining to: low lean muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and muscle weakness. Prefrailty included 2, while frailty included ≥3 conditions. 

Results: The prevalence of prefrailty and frailty was 28% and 13%, respectively. Predictors of pre-frailty and/or frailty: After adjusting for age at enrollment, sex, race, education and employment status, survivors with low income (annual household income <$50,000/ annual personal income <$20,000) were 3.2 times more likely to report pre-frailty and/or frailty (OR=3.2, 1.5-6.9, p=0.003); furthermore, allogeneic HCT survivors with a history of cGvHD were 2.7 times more likely to report pre-frailty and/or frailty (OR=2.7, 1.2-6.3, p=0.02) than autologous HCT survivors.  Predictors of frailty: Allogeneic HCT survivors with cGvHD were significantly more likely to report frailty than autologous HCT survivors (29% vs. 10%, p=0.004), but the prevalence rate for frailty among allogeneic HCT survivors without cGvHD was comparable to autologous HCT survivors (14% vs. 10%, p=0.4).  Multivariable logistic regression revealed that allogeneic HCT survivors with cGvHD were 4.6 fold more likely to report frailty than autologous HCT survivors (OR=4.6, 1.6-13.2, p=0.004). Of note, age at HCT, age at study participation, race/ ethnicity, year of HCT, and diagnosis were not associated with frailty.  

Conclusions:  Our study demonstrates that the prevalence of frailty among older survivors of allogeneic HCT with a history of cGvHD is about three times that seen among older individuals in the general population, as well as that seen among autologous HCT recipients.  On the other hand, the prevalence of frailty among older survivors of autologous HCT as well as allogeneic HCT recipients without cGvHD is comparable to that in the general population.  Lower income, possibly reflecting compromise in nutrition, or access to medical care, is associated with increased prefrailty and frailty. The study identifies vulnerable populations among older HCT survivors needing close monitoring to prevent and manage morbidity.