Abstract
BACKGROUND: Frailty assessment has emerged as a key component of pre-transplant evaluation. We aimed to validate, across international cohorts, the Hematopoietic Cell Transplantation Frailty Scale (HCT-FS) for the assessment of frailty in adult candidates for allogenic hematopoietic cell transplantation (allo-HCT). HCT-FS is designed for integration into routine workflows using existing resources. METHODS: In this prospective, observational cohort study, we evaluated the performance of HCT-FS, a frailty scale that categorises patients as fit, pre-frail, or frail based on a cumulative weighted score derived from eight variables. We enrolled participants across 16 allo-HCT programmes (one in Canada, 15 in Spain). Eligible participants were all adult patients evaluated for frailty at the centres during the time frames: from the Hans Messner Allo-HCT Program at Princess Margaret Cancer Center (PMCC) in Toronto, Canada (2018-2024; where HCT-FS was developed) and from 15 Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC) centres across Spain (2022-2023). Frailty was systematically assessed in all candidates for a median of 10 min at the first allo-HCT consultation by haematologists or trained nurses using the HCT-FS. The prognostic accuracy of the HCT-FS was assessed by evaluating its ability to discriminate clinical outcomes across frailty categories in the overall cohort and by testing the consistency of these associations within specific patient subgroups. Data were prospectively updated until February 2025. FINDINGS: Overall, 1077 consecutive adult allo-HCT candidates were enrolled and evaluated across the PMCC (n = 734) and GETH-TC (n = 343) cohorts. The median age was 56 years (range 18-76); 411 patients (38.2%) were over 60, and 640 (59.4%) were male. Based on the HCT-FS, 33.4% patients were fit, 53.7% pre-frail, and 12.8% frail. Frailty was associated with longer hospital stays (23, 25, and 28 days for fit, pre-frail, and frail patients, respectively; p = 0.003) and higher ICU admission rates (Day +180: 7.0%, 10.8%, and 20.3% for fit, pre-frail, and frail patients, respectively; p = 0.002). 2-year OS decreased progressively with increasing frailty: 77.2% for fit, 65.7% for pre-frail, and 52.8% for frail (p < 0.001). Corresponding NRM rates were 11.7%, 19.5%, and 32.2%, respectively (p = 0.001). Multivariable analysis confirmed frailty as a predictor of inferior OS and increased NRM, when adjusting for age, comorbidities, performance status, DRI, and donor type. The HCT-FS maintained robust prognostic accuracy across subgroups stratified by age and comorbidity burden. INTERPRETATION: The HCT-FS provided reliable measures of the frailty status of allo-HCT candidates that are informative for transplant outcomes, supporting its potential applicability in clinical practice. Notably, this tool was successfully integrated into clinical practice without additional resources. Future work is needed to further evaluate the applicability of the scale in transplant settings and whether targeted interventions based on can improve transplant outcomes. FUNDING: None.