Hematopoietic stem cell transplantation (HSCT) is used with curative intentions for hematologic neoplasms and other potentially lethal diseases [1]. Improvements in clinical practice, along with the increase in the population life expectancy, have expanded the indications of both autologous and allogeneic HSCT [2].

Frailty is a syndrome characterized by reduced physiological reserve in patients, which in HSCT patients increases the risk of toxicities and reduces post-transplant survival [3–6]. Additionally, frailty has been associated with poor post-HSCT outcomes in both young and old individuals [7].

Thus, identifying and treating frailty in HSCT candidates can improve final transplant outcomes. Different tools have been developed to diagnose frailty, most of which are adapted from validated geriatric frailty scales [6,8]. Nevertheless, a significant number of HSCT candidates are not geriatric patients, limiting the applicability of these scales for younger individuals [6,8].

While frailty scales are being developed for implementation in the HSCT setting, there is still no consensus on the best assessment methodology, target population, cost-effectiveness, and predictive accuracy [9].

Professionals at Princess Margaret's Hospital developed the Hematopoietic Cell Transplantation Frailty Scale, a tool to assess frailty and functionality in HSCT candidates regardless of age. It is a multidimensional assessment composed of eight items specifically selected to be administered in the daily clinical practice, with no additional waiting time for patients and using existing human resources [9,10].

The HCT Frailty Scale corresponds to a quick and easy-to-implement tool that combines functional variables related to frailty along with laboratory biomarkers that categorize adult HSCT candidates into three categories: ‘fit,’ ‘pre-frail’ and ‘frail’ [10].

The HCT Frailty Scale still lacks psychometric studies in the Chilean population. As the validation process is dynamic and continuous, frailty scales acquire greater relevance as they advance and deepen with psychometric studies that allow the strengthening of their use in the daily clinical practice [11]. Therefore, the use of validated instruments tailored to the specific population is recommended for clinical applications. Thus, the objective of this study is to evaluate the psychometric properties such as reliability and validity of the HCT Frailty Scale in a sample of Chilean HSCT candidates, and, subsequently, characterize their sociodemographic and clinical profiles.

This observational study with a cross-sectional design followed the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines [12].

This study demonstrates that the Chilean Spanish version of the HCT Frailty Scale is adequate in terms of internal consistency and construct validity in the assessment of frailty in HSCT.

The sociodemographic background of this study identified a young population with a mean age of 40.5 ± 14.5 years, exhibiting some degree of frailty. This finding is consistent with previous studies that indicated that frailty is not exclusive to the geriatric population [3,5,10]. Additionally, patients with hematological malignancies who are candidates for HSCT may also exhibit this syndrome [5,9,10].

In terms of frailty, the majority of participants were categorized as ‘prefrail’ (n = 48; 47.1%) followed by ‘fit’ (n = 39; 38.2%) and a minority as ‘frail’ (n = 15; 14.7%). Similar results were reported in studies conducted by the original authors of the HCT Frailty Scale. In their initial consultation assessment, 53.4% were classified as ‘pre-frail’, 28.8% as ‘fit’ and 18.2% as ‘frail’ [5,10,19].

The criteria used to assign patients to these categories are summarized in Supplementary Table 1, which details the classification of each HCT Frailty Scale domain (normal versus abnormal) based on established cutoffs, and how these scores determine the overall frailty status.

Regarding the psychometric properties, the scale demonstrated acceptable internal consistency, with Cronbach's alpha values of 0.63 for the total scale. Internal consistency is a measure of the correlation between items in a measurement instrument. Generally, values are acceptable between ≥0.70 and ≤0.95. However, when interpreting the value of the coefficient of internal consistency, it is convenient to take into account the length of the scale. It is generally recommended that scales with ten homogeneous items should achieve an adequate reliability [20]. Nevertheless, many modern scales comprise fewer than ten items. In these cases, internal consistency can still be acceptable with values below 0.70. This was the case in this study, where the HCT Frailty Scale (with eight items) achieved a Cronbach's alpha of 0.63, which is considered acceptable [18].

In this study, construct validity confirmed only one hypothesis related to performance status with results similar to those reported in the study by Salas et al., who found that patients with a KPS <90 were more likely to be frail than those with a higher KPS [9].

Contrary to expectations, the results of this study indicate that frailty is a common syndrome in both patients with HSCT-CI ≥ 3 and those with a HSCT-CI <3. This finding is consistent with Salas et al., who reported that frailty was independent of the initial comorbidity index [19]. This was also the case for patients with both high-very high and low-moderate DRI.

Regarding age, the results of this study show that comparable levels of frailty can be found in both younger (under 60 years) and older adults (≥60 years). Rejecting the initial hypothesis, it was found that young adult candidates for HSCT may also be frail due to multiple factors, such as underlying disease, prior treatments, and existing complications [10,21,22].

Finally, the type of HSCT (autologous or allogeneic) did not influence the frailty score. Similar results were obtained in the study by Singh et al., where similar distributions of frailty domains were observed for autologous and allogeneic HSCT [23]. Considering that most studies on frailty in HSCT have focused exclusively on allogeneic HSCT [10,24] the findings of the present study are noteworthy as a significant percentage of autologous HSCT candidates (57.8%), who may also present pretransplant frailty, was included.

One of the limitations of this study was the absence of published psychometric studies of the HCT Frailty Scale, which restricted the possibility of comparing these findings with other studies. However, a nationally representative sample was involved, evaluating HSCT candidates from all regions of the country.

In addition, it is important to note that although frailty assessments are currently recommended prior to HSCT [4,24,25], they have not yet been systematically incorporated into pre-HSCT evaluations.

Likewise, the implementation of pre-HSCT frailty assessments remains an area of emerging interest and active research [1]. Therefore, this study represents a breakthrough in the area, demonstrating how frailty interacts with key factors in HSCT candidates, and identifying clinically relevant patterns for decision-making in this population.

Finally, as frailty status is dynamic in nature, i.e., the transition from ‘fit’ to ‘pre-frail’ and ‘frail’ is not always linear, it is potentially reversible and can be modified through targeted interventions [26]. Therefore, routine frailty assessment and monitoring is gaining importance in HSCT patients [1,18] and could be a preliminary step in designing specific, multidisciplinary interventions, including prehabilitation and post-HSCT rehabilitation programs. Therefore, the management of this syndrome should focus on its identification, treatment, and prevention of its potential consequences [27] aiming to reduce the negative impact of HSCT on the patient’s quality of life, morbidity, and mortality.

The Chilean version of the HCT Frailty Scale has demonstrated adequate reliability and validity, with a factorial structure that supports its use in assessing frailty in HSCT candidates. Frailty was associated with lower performance status, but not with DRI, HSCT-CI, transplant type, or age.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

None.