title: Physiologic Frailty in Nonelderly Hematopoietic Cell Transplantation Patients: Results From the Bone Marrow Transplant Survivor Study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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
  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.
authors.affiliation: Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis.
authors.forename: Mukta
authors.initials: M
authors.lastname: Arora
authors.affiliation: Department of Population Sciences, City of Hope, Duarte, California.
authors.forename: Can-Lan
authors.initials: CL
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Ness
authors.affiliation: Department of Population Sciences, City of Hope, Duarte, California.
authors.forename: Jennifer Berano
authors.initials: JB
authors.lastname: Teh
authors.affiliation: Comprehensive Cancer Center, Department of Pediatrics, University of Alabama at Birmingham, Birmingham.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wu
authors.affiliation: Comprehensive Cancer Center, Department of Pediatrics, University of Alabama at Birmingham, Birmingham.
authors.forename: Liton
authors.initials: L
authors.lastname: Francisco
authors.affiliation: Department of Population Sciences, City of Hope, Duarte, California.
authors.forename: Saro H
authors.initials: SH
authors.lastname: Armenian
authors.affiliation: Department of Population Sciences, City of Hope, Duarte, California.
authors.forename: Amy
authors.initials: A
authors.lastname: Schad
authors.affiliation: Department of Population Sciences, City of Hope, Duarte, California.
authors.forename: Golnaz
authors.initials: G
authors.lastname: Namdar
authors.affiliation: Department of Population Sciences, City of Hope, Duarte, California.
authors.forename: Alysia
authors.initials: A
authors.lastname: Bosworth
authors.affiliation: Department of Population Sciences, City of Hope, Duarte, California.
authors.forename: Linus
authors.initials: L
authors.lastname: Kuo
authors.affiliation: Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Division of Hematology/Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.affiliation: Comprehensive Cancer Center, Department of Pediatrics, University of Alabama at Birmingham, Birmingham.
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
mesh_terms: D000328:Adult; D019588:Aging, Premature; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006689:Hodgkin Disease / Q000401:mortality / Q000628:therapy; D006801:Humans; D007945:Leukemia, Lymphoid / Q000401:mortality / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy; D008297:Male; D010641:Phenotype; D015995:Prevalence; D012189:Retrospective Studies; D035781:Siblings; D017741:Survivors; D014184:Transplantation, Homologous; D016896:Treatment Outcome