The Impact of Frailty on Outcomes and Quality of Life in Allogeneic Hematopoietic Cell Transplantation: Summary of Results from a Collaborative Prospective Study Conducted on Behalf of the Geth-TC
Authors: Salas Maria Queralt , Solano Maria Teresa , Baile González Mónica , Acera Gómez Marina , Fox Maria Laura , Pérez Artigas Maria del Mar , Santamaria Ana , Quintela González María del Carmen , Sanchez Salinas Andres , Salmeron Camacho Joaquina , Illana Álvaro Veronica , Abdallahi Lefdil Zahra , Fernandez-Luis Sara , Vega Suárez Leddy Patricia , Cornago Javier , Pardo Laura , Villar Sara , Beorlegui Murillo Patricia , Esquirol Albert , Izquierdo Isabel , González Rodriguez Sonia , Mussetti Alberto , Rubira Esperanza Lavilla , López Marin Javier , Filafferro Silvia , Balsalobre Pascual , Sureda Balari Ana Maria 
Published: December 2024

Introduction
Frailty in allo-HCT patients is associated with higher morbidity and mortality, making its assessment before transplantation crucial. Nevertheless, most frailty assessments in allo-HCT settings have utilized complex and time-consuming methodologies, limiting their application in clinical practice.
Thirteen institutions, members of the Spanish Group of Hematopoietic Transplantation and Cellular Therapy (GETH-TC), participated in a multicenter observational study to evaluate the viability and potential usefulness of the HCT Frailty Scale for managing frailty in allo-HCT settings. This abstract summarizes the prospective findings from this collaborative effort.
Methods
From April 2022 to September 2023, 403 adult candidates for allo-HCT were assessed for frailty using the HCT Frailty Scale after providing informed consent. Patents were classified as fit, pre-frail, or frail according to their results. The assessment took place at the first consultation for allo-HCT, at HCT admission, at day +100, and at +1 year. Simultaneously, QoL was measured using the EQ-5D-3L test. Evaluations took 8-10 minutes per patient and were conducted by the HCT teams without additional external resources. Prospective data were updated in July 2024.
Results
The median age of patients was 56 years (range: 18-76), with 88 (21.8%) patients over 64 years old. 260 (65.5%) patients were male, 141 (35.0%) had a KPS &lt; 90%, and 52 (12.9%) had an HCT-CI &gt; 3. Acute myeloid leukemia (n=150, 37.2%) and myelodysplastic syndromes (n=69, 17.1%) were the most prevalent diagnoses. The median time from first consultation to HCT admission was 27 days, and 61 (15.1%) patients from a single institution underwent pre-habilitation. With a median follow-up of 14 months, 87 (21.6%) patients relapsed and 119 (29.5%) died, 72 (17.9%) due to NRM.
At the first consultation, 106 (26.4%) patients were classified as fit, 247 (61.3%) as pre-frail, and 50 (12.4%) as frail. Binary logistic multivariate regression analysis (MVA) indicated that the likelihood of being frail was higher in patients undergoing allo-HCT with active disease (Odds Ratio [OR] 5.92, P=0.003) and with an abnormal Mini-Cog (OR 3.91, P=0.010). However, frailty did not correlate with age (&gt;65), sex, and comorbidities (HCT-CI&gt;3).
At HCT admission, 86 (21.3%) patients were fit, 247 (61.3%) pre-frail, and 70 (17.8%) frail. MVA revealed that frail patients were more likely to have worse KPS (&lt;90%: OR 2.63, P=0.003), with no correlation with age, sex, comorbidities, and disease status (active disease vs. other). Notably, joining a pre-habilitation program decreased the odds of presenting frailty at admission (OR 0.20, P=0.033).
Of the 325 adults who reached 100 days of follow-up, 71 (21.8%) were fit, 192 (59.1%) pre-frail, and 62 (19.1%) frail. Frailty was more probable in patients with grade 3-4 aGVHD (OR 3.11, P=0.017) than in patients without this complication. Nevertheless, frailty could be diagnosed irrespective of age, sex, comorbidities, conditioning regimen intensity, and the use of PTCY-based prophylaxis.
Lastly, among the 172 adults with 1-year follow-up without disease relapse, the proportion of fit patients increased to 41.3% (n=71); 90 (52.3%) patients were pre-frail, and only 11 (6.4%) patients were frail. At this time point, frailty could be diagnosed irrespective of baseline diagnosis and the onset of cGVHD.
Frail patients had lower OS than fit and pre-frail ones regardless of when this syndrome was evaluated (1-year OS of fit, pre-frail, and frail patients at first consultation: 80.3%, 71.0%, and 67.1%, P=0.05; at admission: 87.5%, 71.4%, and 61.2%, P=0.01 and at day +100: 93.9%, 86.3%, and 70.9%, P&lt;0.01; and at 18-month in patients evaluated 1-year after allo-HCT: 98.5%, 95.5%, and 85%, P=0.01). Causes of death among frail patients were mainly due to NRM. Similarly, the QoL of frail patients was worse than that observed in fit and pre-frail ones.
Conclusions
This collaborative study has demonstrated the dynamic nature of frailty in allo-HCT patients and its significant impact on survival and QoL. Frailty assessments conducted efficiently reveal that frail patients face higher risks and worse outcomes, independent of age or comorbidities. Pre-habilitation interventions show promise in reducing frailty before transplantation. Regular frailty monitoring could be integrated to better tailor interventions and improve allo-HCT outcomes.