Frailty Syndrome in Adults Undergoing Autologous Hematopoietic Cell Transplantation. Prospective Study on Behalf of the Grupo Español De Trasplante Hematopoyético y Terapia Celular
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 , Cornago Javier , Pardo Laura , Fernandez-Luis Sara , Vega Suárez Leddy Patricia , Villar Sara , Beorlegui Murillo Patricia , Esquirol Albert , Izquierdo Isabel , González Rodriguez Sonia , Mussetti Alberto , Abuin Blanco Aitor , López Marin Javier , Filaferro Silvia , Bento Leyre , Sureda Balari Anna Maria 
Published: December 2023

INTRODUCTION
During the past two years, sixteen institutions members of the Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC) have undertaken a multicenter and prospective study with the purpose of evaluating the frailty of adults' candidates to autologous HCT (auto-HCT) and of investigating the effect of frailty in transplant outcomes.
METHODS
All patients consulted for auto-HCT were eligible to be included in the study after providing informed consent. Frailty was evaluated at first consultation, at admission, and after the stem cell infusion, using the HCT Frailty Scale (Salas et al. BMT 2023), designed classify candidates for allogeneic HCT into fit, pre-frail and frail categories ( Table 1). The frailty assessment was made by the hematologists and nurses team as part of the clinical practice and utilizing existing resources. The median time to complete the evaluation ranged from 8 to 10 minutes. As an extension, this study includes the evaluation of patient´s quality of life (QoL) using the EQ-5D-EL questionnaire. QoL was measured at HCT admission and day +100 after the stem cell infusion.
This study has no external funding. The results obtained from the frailty assessment were not used to determine HCT eligibility and/or to design the HCT process.
RESULTS
This study includes 380 consecutive adult candidates for auto-HCT who have been evaluated for frailty in the sixteen participating institutions between February 2021 and May 2023.
Overall, the median age was 58 (range, 18-76) and 219 (57.6%) were males. Multiple myeloma or other plasma cell discrasias (PCD) (n=213, 62.1%) and lymphoproliferative disorders (SLP) (n=121, 31.8%) were the most prevalent baseline diagnosis. Prior to auto-HCT, 104 (33.8%) out of 307 adults had an KPS&lt;90% and 35 (12.4%) out of 282 an HCT-CI&gt;3. All patents included underwent their auto-HCT during the study period, and in only 20 (5.3%) of the cases, the standard doses of the conditioning regimen were required to be adjusted secondary to the patient´s condition, age or comorbidities.
The first consultation was mostly performed before the stem cell collection. At first consultation, 108 (28.4%) adults were classified as fit, 203 (53.4%) as pre-frail, and 69 (18.2%) as frail. Frail patients were more likely to be older than 60 (OR 5.3, p&lt;0.001), to have a KPS&lt;90% (HR 5.80, p&lt;0.01), and an abnormal Mini-Cog test (&lt;3) (OR 5.81, p=0.0271). The probability of being frail was not affected by sex (HR 1.7, p=0.173), comorbidities (HCT-CI&gt;3) (p=0.196), or underlying diagnosis (multivariate binary regression analysis).
Frailty at first consultation was not associated with a more prolonged HCT hospitalization (p=0.663) or higher readmissions (p=0.579). However, a non-significant trend to lower OS was observed in frail patients undergoing auto-HCT than in the rest [ 1-year OS of fit, pre-frail, and frail adults: 98.5%, 95.6%, and 84.4% (p=0.072)] ( Table 1). The impact of frailty in QoL was also investigated. As shown in Table 2, compared with fit patients, pre-frail and frail adults had worse score values throughout all the variables included questionnaire.
Since PCD and SLP are the most prevalent indications for auto-HCT, trends on frailty were investigated separately on these subgroups of patients . Trends on frailty were examined and reported in Table 1. At first consultation, the proportions of fit, pre-frail, and frail adults were similar between the two groups (p=0.896). At HCT admission, the proportion of frail patients with PCD tend to be higher than in the other group (16.6% vs.9.9%, p=0.051). Nevertheless, at day +100, frailty stages were again similar between the two study groups. Lastly, when the impact of frailty in OS was investigated in these two subgroups of patients, the negative effect of this syndrome in post-transplant outcomes was only observed in patients with PCD (p=0.012).
CONCLUSIONS
This study validates the applicability of the HCT Frailty Scale in adult candidates for auto-HCT. At first consultation, frailty had an incidence of 18% being more prevalent in older adults and with worse performance status. Moreover, it´s presence during the post-transplant process was associated with worse QoL.
Preliminary data shows that frailty at first consultation correlates with lower OS in patients with PCD. Further analyses will be conducted to better investigate this result.