Results from this multicenter study confirm the predictive power of the HCT Frailty Scale for transplant outcomes, similar to the original Canadian study (26, 27). The scale can be integrated into regular clinical practice by the transplant team with minimal time and resources. Importantly, the study reveals the dynamic nature of frailty in allo-HCT candidates, suggesting potential reversibility with pre-transplant interventions. These findings underscore the potential for combining frailty evaluation using the HCT Frailty Scale with tailored pre-habilitation programs to improve patient frailty before transplantation and, ultimately, improve transplant outcomes.
In geriatric medicine, patients' frailty status is viewed as a dynamic continuum, generally categorized into three groups: non-frail (fit), vulnerable (pre-frail), and frail, aiming to enhance clinical practice (35, 36). The HCT Frailty Scale was developed to assess allo-HCT candidates' frailty, with a focus on potentially reversing pre-frail patients' progression toward frailty. Interestingly, our study involving 384 transplanted patients across 15 GETH-TC-affiliated centers, proportions of fit, pre-frail, and frail patients closely mirrored those reported by the Princess Margaret Cancer Center study, validating the scale's discrimination power.
Following the practice at the Canadian Institution, the HCT Frailty Scale was applied to all candidates regardless of age (26, 27). While the proportion of older adults was higher in the pre-frail and frail categories, the assessment of frailty among patients under 60 years old revealed a notable incidence of 8.8%. These finding highlights that hematologic diseases, intensive treatments, and comorbidities can precipitate or accelerate frailty development (36–38), and recommend the evaluation of frailty beyond geriatric HCT candidates.
This study underscores the dynamic nature of frailty, traditionally associated with geriatric populations, and its potential reversibility among allo-HCT candidates (36, 37, 39, 40). Importantly, frail and pre-frail patients consistently showed lower OS and higher NRM rates compared to fit patients, regardless of when they were evaluated (first consultation and HCT admission). This highlights the significant influence of frailty on outcomes, outweighing factors such as chronological age, KPS, or comorbidities.
Although the number of patients undergoing pre-habilitation was limited, results presented in this study hold implications for the HCT community, emphasizing the importance of implementing pre-transplant interventions to either reverse frailty or mitigate its adverse impact on transplant outcomes. Additionally, since transition of patients across frail categories was observed regardless the initial frailty group, it's advisable to extend the recommendation for pre-habilitation to all candidates for allo-HCT, and to individualize the intervention plan to the frailty state of patients at first consultation to increase its effectiveness.
QoL at HCT admission was affected by the frailty state of patients. These results are considered relevant as impairment on QoL may affect patients' ability to cope with the expected isolation during HCT admission and with potential medical issues occurring during the post-transplant phase. QoL is a multifaceted concept, and limited studies have still investigated the association between frailty and QoL, most of them conducted in community-dwelling older adults (41). Given the ongoing nature of our study, further exploration between frailty and QoL will be conducted in future analysis specially in transplant survivors.
The information provided by the HCT Frailty Scale was not utilized for altering transplant platforms and/ or modifying supportive care. These are topics left for future research, and would complement those in the way of integrating frailty information in the design of pre-habilitation plans. Although publications support the importance of rehabilitation and physical activity after allo-HCT to enhance transplant results (20, 42–47), there is limited information about the effect of implementing multidimensional interventions for HCT candidates (21). But reasonably, the outpatients’ physical activities should be adapted to the frailty state of patients, something that it is not generally happening so far.
A primary study limitation is the relatively short follow-up period of the patients involved. However, the study is still ongoing with frailty evaluations after allo-HCT, so updated results will be presented in future studies. Another limitation is the relatively small number of patients undergoing pre-habilitation, all of them from a single institution. The results, however, are encouraging. As pre-habilitation programs become more common in allo-HCT practice, the timing of frailty information will become crucial for predicting transplant outcomes. According to Figs. 2 and 3, frailty data collected at first consultation provides sufficient information on outcomes in non-pre-habilitated patients. However, for pre-habilitated patients, data collected at admission is more informative than at first consultation, indicating that pre-habilitation changes the dynamics of frailty in a non-tendential way.
In conclusion, the study effectively implements the HCT Frailty Scale in HCT programs within a different population cohort and healthcare system than the one where it originated in Canada (26, 27). Given that the frailty status of allo-HCT candidates predicts transplant outcomes and frailty is dynamic and potentially reversible, preliminary evidence supports the usefulness of the frailty evaluation at first consultation for designing personalized pre-habilitation programs to be implemented until HCT admission.
Our findings are relevant considering the detrimental impact of frailty on transplant outcomes, and highlight the importance of diagnosing frailty and implementing interventions for all candidates for allo-HCT. Since the effectiveness of pre-habilitation can be evaluated with frailty scales at HCT admission, this study highlights the need for implementing resource-efficient evaluations such as the HCT Frailty Scale.