Physiologic Frailty in Nonelderly Hematopoietic Cell Transplantation Patients

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.

Chronic disease burden and frailty in survivors of childhood HSCT: a report from the St. Jude Lifetime Cohort Study

“…Initially described in geriatric populations, frailty is recognized as an important predictor of additional morbidity and mortality in childhood cancer survivors and in adult HSCT recipients. 10,23 A recent study in adult HSCT survivors (mean age, 42 years; median time since transplant, 7.9 years) described a higher prevalence (8.0%) of frailty among HSCT survivors than among siblings (2.0%) and reported an association between frailty and mortality. 23 …”

Prediction of cardiovascular disease among hematopoietic cell transplantation survivors

“…[45][46][47][48] Future CVD risk-reduction strategies for HCT survivors will benefit from a personalized approach, taking into consideration the physical limitations associated with complications such as GVHD and the burden of other chronic health conditions that develop after HCT. 9,49,50 We acknowledge that as in other risk prediction models, there may be variables that are unaccounted for in our models. This may be especially true for HF prediction, as the AUC and C-statistics were consistently lower for HF than for CAD (0.66 to 0.71 [HF] vs 0.75 to 0.82 [CAD]).…”

Frailty in Hematologic Malignancy

“…(25, 26) There are a number of other screening tools available to help clinicians identify those in need of further assessment including: FRAIL (Fatigue, Resistance, Ambulation, Illnesses, Loss of Weight), (27) Groningen Frailty Indicator, (28) and the Clinical Frailty Scale. (29) Frailty assessments, are commonplace in older adults, however it is necessary to denote that frailty is prevalent in childhood cancer survivors and associated with an increased risk of mortality in young hematopoietic cell transplant populations(30, 31). …”

“…(58) The prevalence of frailty and pre-frailty are 28% and 51% respectively, in adults over age 50 prior to receiving allogeneic HCT. (59) In 203 patients with median age of 58 years who underwent allogeneic HCT, limitations in instrumental activities of daily living (HR 2.38; P<0.001), slow gait speed (HR 1.80; P=0.01), and low mental health by short-form-36 mental component (HR 1.67; P=0.01) pre-HCT were associated with worse survival (60).…”