Editor's Note: With advancements in medicine, allogeneic hematopoietic cell transplantation (allo-HCT) has become a hope for a cure for many patients with high-risk hematologic malignancies. However, the high risks and significant heterogeneity associated with the transplant process pose severe challenges to clinical decision-making. How to accurately assess a patient's ability to tolerate the stress of transplantation and predict their prognosis is a key focus of the global hematology community. At a recent European Hematology Association (EHA) Annual Meeting, Professor Maria Queralt Salas from the Hospital Clinic de Barcelona, on behalf of a multicenter research team from Canada and Spain, systematically presented their breakthrough research on an innovative assessment tool: the Hematopoietic Cell Transplantation Frailty Scale (HCT-FS). This study not only confirms the importance of frailty assessment in the transplant field but also provides a standardized protocol that can be efficiently implemented in busy clinical settings.

Opportunities and Challenges in Allogeneic Transplantation: The Urgent Need for Precise Assessment

Professor Maria Queralt Salas pointed out at the beginning of her report that as a potentially curative therapy, the eligible population for allo-HCT is continuously expanding to include more older patients and those with multiple comorbidities. This trend has led to a significant increase in the heterogeneity of transplant candidates. Traditional assessment methods, such as the Karnofsky Performance Status (KPS), are no longer sufficient to comprehensively capture a patient’s physiological reserve and ability to withstand stress.

“Frailty,” a syndrome characterized by a decline in physiological reserve and a reduced ability to recover after stress, has been proven to be a key factor affecting transplant outcomes. Professor Salas emphasized, “Frailty is not synonymous with old age. The hematologic disease itself and its treatment process can induce or accelerate a state of frailty in adult patients of any age.” Although previous studies have shown a correlation between pre-transplant frailty and poorer survival outcomes, the lack of uniform, time-efficient assessment methods, often limited to the elderly population, has severely restricted the routine clinical application of frailty assessment. Therefore, it has become particularly urgent to develop a frailty assessment tool specifically designed for the transplant setting that is simple, practical, and applicable to all adult patients.

The HCT Frailty Scale (HCT-FS): A Rapid Assessment Tool Specifically Designed for Transplant Clinics

Against this backdrop, researchers at the Princess Margaret Cancer Center in Canada first designed the HCT Frailty Scale. The core design philosophy of this scale is “efficiency, practicality, and integration,” aiming to utilize existing clinical resources to complete the assessment within 10 minutes by a hematologist or nurse coordinator, without the need for an extra appointment. The HCT-FS integrates eight key variables to construct a multidimensional assessment system:

1.Clinical Frailty Scale

2.Instrumental Activities of Daily Living

3.Timed Up and Go Test

4.Grip Strength Test

5.Self-rated health questionnaire

6.History of falls

7.Serum albumin level

8.C-reactive protein level

Professor Salas explained, “The weights of these variables were determined based on their independent impact on Overall Survival (OS), through a prospective data analysis of the first 298 patients.” Based on the composite score, patients are clearly classified into three categories: “Fit,” “Pre-frail,” and “Frail.”

Core Research Findings: Frailty Status Significantly Impacts Transplant Survival Outcomes

This large-scale prospective study, jointly conducted by 15 transplant centers in Canada and Spain, enrolled a total of 1077 allo-HCT candidates. The results showed that approximately 30% of patients were classified as “Fit,” 13% as “Frail,” and the majority as “Pre-frail.”

The research team found a strong correlation between frailty status and transplant prognosis:

Survival Outcomes: Compared to the fit group, the pre-frail and frail groups had significantly shorter overall survival and significantly higher Non-Relapse Mortality (NRM). Importantly, frailty status was not associated with the risk of disease relapse, indicating that its main impact is on the patient’s ability to tolerate transplant-related toxicities rather than on tumor control.

Clinical Resource Utilization: Frail patients had longer initial hospital stays, higher readmission rates, and a higher proportion of admissions to the Intensive Care Unit (ICU). This finding strongly supports the definition of frailty—that is, the body’s impaired ability to restore homeostasis when facing a major stressor like transplantation.

In multivariate analysis, the predictive power of the HCT-FS surpassed that of several traditional metrics. Professor Salas specifically noted, “When we included both HCT-FS and KPS scores in the model, HCT-FS remained a strong independent predictor of OS and NRM, while KPS lost its statistical significance. This demonstrates that HCT-FS can more accurately identify high-risk patients.”

Multidimensional Validation: The Generalizability and Superiority of the HCT-FS

To ensure the broad applicability of the scale, the research team conducted in-depth subgroup analyses, with convincing results:

Cross-national Validation: The proportion of frail patients and the negative impact of frailty on prognosis were highly consistent between the Princess Margaret Cancer Center in Canada and the various transplant units in Spain, confirming the stability and reliability of the HCT-FS across different healthcare systems.

Age Independence: The study overturned the traditional notion that “frailty is only associated with old age.” Data showed that 13% of young patients aged 18 to 40 were classified as frail, and the proportion was the same (13%) among patients over 60. More critically, the negative impact of frailty on survival was identical across young, middle-aged, and older patient groups, underscoring the necessity of frailty assessment for patients of all ages.

Independence from Comorbidities: Although frailty was more prevalent in patients with a higher comorbidity burden, frailty status was an independent poor prognostic factor even in patients with few comorbidities. This indicates that frailty assessment provides additional prognostic information beyond conventional comorbidity indices.

Expert Perspective and Clinical Application Outlook: From Precise Assessment to Proactive Intervention

During the Q&A session, in response to the question, “How should we use this information to help frail patients?” Professor Salas shared her team’s practical experience. She stated that identifying frailty is not the end point, but the starting point for intervention. “We have confirmed that frailty is dynamic and modifiable. Therefore, we have implemented a ‘Prehabilitation’ program for our patients. Starting from the first outpatient visit, we help patients ‘train’ for the transplant through physical exercise and other means to improve their physiological condition.” This proactive intervention model continues throughout the transplant process, transitioning to a “Rehabilitation” program after admission, with repeated HCT-FS assessments to monitor the effectiveness of the intervention. Professor Salas further proposed a more profound consideration: “We believe that oncologists should pay attention to this variable when treating the primary disease. Ideally, patients should not be frail when they arrive at the transplant clinic; they should have received intervention and support at a much earlier stage.”

The next phase of the research will delve deeper into the key drivers of frailty and attempt to introduce frailty assessment at the time of diagnosis to track its dynamic evolution, providing a basis for earlier and more precise interventions.

In conclusion, this large-scale international collaborative study reported by Professor Maria Queralt Salas successfully validates the immense value of the HCT-FS as a rapid, reliable, and powerful prognostic tool in the field of allogeneic hematopoietic cell transplantation. It not only provides clinicians with a “discerning eye” to accurately identify high-risk patients beyond age and traditional scores but, more importantly, it drives a paradigm shift in the transplant field from passive risk stratification to proactive state intervention. This achievement is a vivid embodiment of the precision medicine concept in hematology, bringing new hope and direction for optimizing transplant decisions and improving patient outcomes.