FAC-HCT Scale Integrating Frailty Stratifies Survival Before Allo-HCT

A new composite scoring tool that combines frailty, chronological age, and comorbidity burden into a single pretransplant assessment successfully stratified patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) into 3 distinct risk groups with significantly different overall survival (OS) probabilities, according to data from a multicenter international study presented at the European Hematology Association (EHA) 2026 Congress in Stockholm, Sweden.¹

The FAC-HCT scale (Frailty, Age, and Comorbidity for Hematopoietic Cell Transplantation) identified 2-year OS rates of 79%, 63%, and 44% for low-, intermediate-, and high-risk patients in a training cohort, with nearly identical stratification in an independent external validation cohort: 75%, 62%, and 38%, respectively.

“Frailty adds independent prognostic value beyond traditional transplant assessments, supporting its incorporation into routine pretransplant evaluation,” said María Queralt Salas, MD, of Clínic Barcelona and the Grupo Español de Trasplante de Progenitores Hematopoyéticos y Terapia Celular (GETH-TC), who presented the data. “This scale demonstrated robust external validation across 2 cohorts with different baseline characteristics, highlighting its reproducibility, generalizability, and potential utility for clinical decision-making and patient counseling.”

Rationale: Beyond Age and Comorbidity

The expanding use of allo-HCT, supported by progressive reductions in nonrelapse mortality (NRM) from approximately 40% in the late 1980s to 10% to 20% in the modern era,² has broadened eligibility to older patients and those with greater comorbidity burdens, creating a more heterogeneous population of transplant candidates. Salas argued that traditional pretransplant assessments relying on chronological age and the HCT–Comorbidity Index (HCT-CI) may not fully capture this heterogeneity, as age alone is not synonymous with health status and comorbidities may be well controlled at the time of transplantation.

Prior work has shown that frailty syndrome, defined as a “a medical condition characterized by a multisystem deregulation leading to a reduced ability to reestablish homeostais in response to stress,”³ can affect from 15% to 33% of allo-HCT candidates, a rate substantially higher than the approximately 10% observed in community-dwelling individuals over 65 years of age, and is associated with higher transplant-related mortality. The FAC-HCT scale was designed to integrate frailty formally into the pretransplant evaluation.

Study Design and Cohorts

This retrospective multicenter study included 1075 adult allo-HCT candidates who underwent frailty assessment using the HCT Frailty Scale (HCT-FS) between 2018 and 2024.¹ No patients received prehabilitation, which was a deliberate design choice to allow unmodified baseline frailty to inform scale development.

The training cohort comprised 734 patients transplanted at Princess Margaret Cancer Centre (PMCC) in Toronto, Canada, with a median follow-up of 40 months. The external validation cohort comprised 341 patients transplanted at 15 member institutions of the GETH-TC in Spain between 2022 and 2024, with a median follow-up of 23 months. The 2 cohorts differed significantly in baseline characteristics: PMCC patients had a higher median age (59 vs 55 years), a higher proportion of acute myeloid leukemia diagnoses (50.5% vs 37.5%), a greater use of reduced-intensity conditioning (67.5% vs 52.5%), and more frequent posttransplant cyclophosphamide (PTCy)-based graft-vs-host disease (GVHD) prophylaxis (85% vs 57%).

Scale Construction

The HCT-FS, originally developed at PMCC between 2018 and 2020, evaluates 8 variables: the Clinical Frailty Scale, instrumental activities of daily living, the Timed Up and Go Test, a grip strength test, self-rated health questions, falls in the last 6 months, serum albumin level, and C-reactive protein. It then produces a continuous frailty index from 0 to 10.5, classifying patients as fit (≤1), pre-frail (1.5-5), or frail (≥5.5). The scale can be completed in approximately 10 minutes using existing transplant unit resources and is designed to be administered by hematologists or transplant nursing staff.

To construct the FAC-HCT scale, the investigators first confirmed in the training cohort using a LASSO penalized regression model that age, HCT-CI, and HCT-FS frailty classification were each independent predictors of OS. Patients aged 41 to 65 years had a significantly higher risk of mortality compared with those 40 years or younger (HR, 1.56; 95% CI, 1.07-2.27; P =.022), as did those over 65 years (HR, 1.81; 95% CI, 1.21-2.70; P =.003). An HCT-CI score above 2 (vs 0-2) was also independently associated with mortality (HR, 1.43; 95% CI, 1.10-1.84; P =.007), as were pre-frail (HR, 1.44; 95% CI, 1.07-1.93; P =.016) and frail (HR, 2.39; 95% CI, 1.65-3.47; P <.001) status vs fit.

Points were assigned to each variable proportionally to its hazard ratio relative to frailty, yielding a composite score that stratifies patients into low (0-5 points), intermediate (5.5-10 points), and high (>10 points) risk groups. Among all 1077 assessed patients, 33% were fit, 54% were pre-frail, and 13% were frail.

Outcomes Across Risk Groups

In the Canadian training cohort, the scale stratified patients into 3 groups with significantly different OS, relapse-free survival, and NRM. Two-year NRM was 8%, 18%, and 29% for low-, intermediate-, and high-risk patients, respectively, with the primary causes of death in the high-risk group being transplant-related rather than disease relapse. The cumulative incidence of relapse was 11%, 18%, and 16%, respectively, indicating that survival differences were driven predominantly by NRM rather than disease recurrence.

In the Spanish validation cohort, 2-year NRM was 10%, 25%, and 32% for the 3 risk groups, and 2-year OS was 75%, 62%, and 38%, highly consistent with training cohort findings. In the combined multivariable analysis of all 1075 transplanted patients, the FAC-HCT scale remained an independent predictor of OS after adjustment for disease risk index, conditioning intensity, donor type, and GVHD prophylaxis. Intermediate-risk patients had significantly higher mortality than low-risk patients (HR, 1.82; 95% CI, 1.37-2.42; P <.001), as did high-risk patients (HR, 2.76; 95% CI, 2.01-3.81; P <.001).

Salas also noted during the question-and-answer session that prehabilitation, now standard of care at her institution, can improve patient fitness and enable reclassification to a lower risk category, and that frailty reassessment at the time of transplant admission is recommended to capture changes in fitness between evaluation and procedure.

REFERENCES

1. González MB, Moya TA, Vlasov M, et al. Development and validation of the FAC-HCT Scale (Frailty, Age and Comorbidity) to predict overall survival after allogeneic hematopoietic cell transplantation. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S265.

2. Penack O, Peczynski C, Mohty M, et al. How much has allogeneic stem cell transplant-related mortality improved since the 1980s? A retrospective analysis from the EBMT. Blood Adv. 2020;4(24):6283-6290. doi:10.1182/bloodadvances.2020003418

3. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-M156. doi:10.1093/gerona/56.3.m146