Is Age No Longer a Barrier to Allogeneic Hematopoietic Stem Cell Transplantation?

In this issue of Transplantation, Fernandez-Luis et al1 evaluated the clinical outcomes in patients aged 65 y and older who received allogeneic hematopoietic stem cell transplantation (allo-HSCT). They concluded that allo-SCT was safe and effective in this aged population and proposed a simplified scoring system to risk stratify for transplantation-related mortality and to determine the indication of allo-HSCT in the elderly. Allo-HSCT is a potential curative treatment for various hematological malignancies. Historically, the indication of allo-HSCT was limited to the younger patients due to significant toxicity directly related to the transplantation procedures. However, HSCT eligibility has expanded to include the elderly with the introduction of less toxic conditioning regimens and the improvement in supportive care. As the aging population increases, the number of older patients who are potential HSCT candidates is likely to continue growing. Nonetheless, older patients continue to face barriers to allo-HSCT access, since chronological age remains a significant limiting factor for referral to the HSCT center.2 Aging is characterized by a decline of physiological integrity and function. Geriatric assessment is a comprehensive measurement of health, including physical function, mental status, cognition, nutrition, and social support in the elderly (Figure 1). Several methods of geriatric assessment have been proposed to risk stratify for transplantation-related morbidity and to determine the indication of allo-HSCT in the elderly.3 However, geriatric assessments usually take 20–30 min and are difficult to perform without expert clinical support staff in clinical practice, and furthermore, no standardized geriatric assessment has yet been established.4FIGURE 1.: Traditional risk assessment and geriatric assessment for allo-HSCT. Traditional assessments (left) include age, performance status, comorbidity, disease risk, condition intensity, and so on. Geriatric assessment (right) is a comprehensive measurement of health, including physical function, mental status, cognition, nutrition, and social support in the elderly. HSCT, hematopoietic stem cell transplantation.In contrast to the geriatric-specific assessments mentioned earlier, Fernandez-Luis et al1 demonstrated that a traditional risk assessment, including Hematopoietic Cell Transplantation Specific Comorbidity Index, Disease Risk Index, and the patient’s functional status with the Eastern Cooperative Oncology Group, is useful to estimate transplant outcomes in elderly patients.1 These have been commonly utilized risk assessments of allo-HSCT regardless of patient age. Importantly, in univariate analysis, age was not a risk factor. Such a traditional assessment is easy to perform in clinical practice and could help to risk stratify for transplantation-related morbidity and determine the indication of allo-HSCT in the elderly. However, there are several limitations. The majority of the patients included in this study were 65–69 y with fewer patients aged 70 y and older. A recent German study comparing transplant outcomes in patients aged 60–69 y and those aged 70–79 y showed significantly higher nonrelapse mortality and significantly less overall survival in the elderly patient population.5 In that study, multivariate analysis for survival and nonrelapse mortality showed that age, disease type and status, comorbidity, and Karnofsky score as independent risk factors.5 Therefore, it remains unclear if chronological age is no longer an absolute barrier to allo-HSCT. Larger studies including patients aged 70 y and older are required to answer the long-standing question. A recent study demonstrated that the age of the host bone marrow environment could influence epigenetic changes of donor cells.6 However, so far, there is no clear clinical evidence of impaired engraftment in elderly patients. Several decades ago, the age limit of allogeneic HSCT was only 40–45 y but now it exceeds 70 y. Improvement of individual health consciousness and medical and health care systems is now extending the healthy life expectancy. Progress in supportive care and transplant procedures makes allogeneic HSCT safer. The age limit of HSCT will be further increased.