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Longitudinal trajectory of frailty in blood or marrow transplant survivors: Report from the Blood or Marrow Transplant Survivor study
Arora, M., Chen, Y., Wu, J., Hageman, L., Ness, E., Kung, M., Francisco, L., Bosworth, A., Weisdorf, D. J., Forman, S. J., et al
Cancer. 2020
Abstract
BACKGROUND Blood or bone marrow transplantation (BMT) survivors with frailty are at a higher risk of subsequent mortality. Longitudinal trends in the frailty state are not known and could help identify vulnerable subpopulations at risk of subsequent adverse events. METHODS This study included a cohort of 470 autologous and allogeneic BMT recipients who had survived =2 years after BMT and completed a baseline questionnaire (t1) at a median of 7.3 years after BMT and a follow-up questionnaire (t2) 13.2 years after t1. The main outcome was change in frailty state between t1 and t2. Frailty phenotype was defined as exhibiting =3 of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The following categories of change in frailty state were evaluated: worsened, improved, and stable. RESULTS Of the 470 participants, 36.4% were aged =60 years at t1, and 50.6% were men. The prevalence of frailty increased from 4.8% at t1 to 9.6% at t2. Worsening was observed in 18.8% of patients, and improvement was reported in 9.7%. Pre-BMT exposure to vincristine (odds ratio [OR], 2.1; 95% CI, 1.3-3.39) was associated with worsening. Female sex (OR, 1.5; 95% CI, 0.93-2.4) was associated with a trend toward worsening. Pre-BMT exposure to vincristine (OR, 2.79; 95% CI, 1.44-5.43), a history of chronic graft-versus-host disease (OR, 2.58; 95% CI, 1.2-5.5), and grade 3 and 4 chronic health conditions at t1 (OR, 2.1; 95% CI, 1.08-4.33) were associated with frailty at t2. CONCLUSIONS In a cohort of BMT survivors who were followed longitudinally for a median of 20.6 years from BMT, the frailty status worsened for approximately20% over a 13-year timespan. BMT survivors who are at risk for worsening frailty could benefit from targeted interventions.
2.
Physiologic Frailty in Nonelderly Hematopoietic Cell Transplantation Patients: Results From the Bone Marrow Transplant Survivor Study
Arora, M., Sun, C. L., Ness, K. K., Teh, J. B., Wu, J., Francisco, L., Armenian, S. H., Schad, A., Namdar, G., Bosworth, A., et al
JAMA Oncology. 2016;2(10):1277-1286
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Abstract
Importance: Frailty results in decreased physiological reserve and diminished resistance to stressors; approximately 10% of those in the elderly population (those >65 years) are frail. High-intensity treatments and complications after hematopoietic cell transplantation (HCT) injure normal tissues and may increase the risk of frailty even among nongeriatric HCT patients. Objective: To determine the prevalence of frailty in young adult HCT patients (18- to 64-year-olds) and siblings; and the impact of frailty on subsequent mortality in HCT survivors. Design, Setting, and Participants: This cohort study, conducted in August 2015 examined 998 HCT survivors, who underwent transplant procedures between 1974 and 1998, who have survived at least 2 years after HCT, and 297 frequency-matched siblings. The study was performed at City of Hope or University of Minnesota with participants completing surveys at home or in the clinic. Hematopoietic cell transplantation survivors and siblings participating in the Bone Marrow Transplant Survivor Study (BMTSS) completed a frailty survey between February 13, 1999 and June 15, 2005 (median time since HCT: 7.9 years); HCT survivors were followed for subsequent mortality (median: 10.3 years from survey). Main Outcomes and Measures: Prevalence and predictors of frailty; impact of frailty on subsequent mortality in HCT survivors. Frailty phenotype defined as exhibiting 3 or more of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The national Death Index, Social Security Death Index and medical records were used for mortality assessment as of December 21, 2011. Results: The 998 HCT survivors were a mean (SD) of 42.5 (11.6) years of age, and the 297 matched siblings were 43.8 (10.9) years of age. The prevalence of frailty among young adult HCT patients exceeded 8%. The HCT survivors were 8.4 times more likely to be frail than their siblings (95% CI, 2.0-34.5; P=.003). Among HCT recipients, allogeneic HCT recipients with chronic graft-vs-host disease (GvHD) were at increased risk of frailty compared with autologous HCT (OR,15.02; 95% CI, 6.6-34.3; P<.001); resolved chronic GvHD (OR, 2.7; 95% CI, 1.1-6.9; P=.04). Cumulative incidence of subsequent all-cause mortality was 39.3% and 14.7% at 10 years for HCT recipients with and without frailty, respectively (P<.001). Frailty was associated with a 2.76-fold (95% CI, 1.7-4.4; P<.001) increased risk of subsequent mortality after adjusting for relevant prognosticators. Conclusions and Relevance: The prevalence of frailty among young-adult HCT survivors approaches that seen in the elderly general population. Frail HCT survivors are at increased risk of subsequent mortality when compared with nonfrail survivors. This study identifies vulnerable populations needing close monitoring to anticipate and manage morbidity and prevent mortality.