Geriatrics assessment in older adults referred for hematopoietic cell transplantation

Hematopoietic cell transplantation (HCT) is an indicated therapy for several hematologic diseases common in older adults. The average age at HCT is increasing, with 26% of allogeneic transplant recipients in 2019 being older than 65, compared with 9% in 2009. While older transplant patients benefit from the positive outcomes of HCT,1-3 they are at risk of increased morbidity and mortality4-6 due to multiple factors including multimorbidity, frailty and functional decline. As HCT becomes more prevalent among older adults, geriatricians and oncologists must collaborate to best identify patients will benefit most from HCT. Geriatric assessment (GA) is a multidimensional assessment designed to evaluate an older person's physical health, cognition, mental health, functional status, and socioenvironmental circumstances. Recent data shows GA improved outcomes in the general population,7-10 and that pre-transplant GA improves outcomes among patients undergoing HCT.5 It is not clear, however, whether routine pre-transplant GA can help in selecting patients who will most benefit from HCT while minimizing adverse outcomes. Our study investigates the feasibility of incorporating a baseline GA at the time of the initial evaluation for allogeneic transplant at our bone marrow transplant (BMT) program. We hypothesized that patients with lower scores on a GA at the time of referral to our BMT program would be less likely to undergo HCT and would have worse outcomes if they did undergo HCT. Between November 2018 and July 2020, 54 patients ≥60 years of age referred to Stanford for allogeneic HCT underwent a GA during their initial pre-transplant appointment. In this context, the term GA refers to the evaluation by an individual geriatrician (VSP) in conjunction with trained medical assistants (MA). The GA consisted of the Montreal Cognitive Assessment (MOCA), Vulnerable Elders Survey (VES-13), Patient-Reported Outcomes Measurement Information System (PROMIS), and the timed up and go (TUG). Assessments were only performed if there was a trained MA available in clinic on a given day. Results of the GA were not shared with the medical team or used to inform treatment decisions. Patients who underwent HCT were followed prospectively via the Stanford BMT Database. All other data were collected retrospectively through chart review using the Stanford Research Repository. Our primary outcome was undergoing HCT, and secondary outcome was mortality. Continuous variables were compared using t test (parametric) or Mann–Whitney U (nonparametric) test. Categorical variables were compared using the Fisher's exact test. This study was approved by the Stanford IRB. Fifty-four patients underwent a GA at their initial pre-transplant appointment, which took an average 20 min to complete. Seventeen of the 54 patients underwent HCT. The median age of the cohort was 71 (IQR 62–77) and was not significantly different between groups (69.6 vs 70.3, p = 0.6). There was no association between any GA element and subsequent HCT (Figure 1). The 1-year mortality was 53% (9/17) for those patients who received HCT and 27% (10/37) for those who did not receive HCT (p = 0.22, NS). The primary cause of death among patients who underwent HCT was relapse of their malignancy (4), followed by acute graft versus host disease (2). Among patients who did not undergo HCT, the primary cause of death was infection (4). The baseline Global Physical Health Score was associated with mortality, with patients with higher scores more likely to die by 1 year (median 10 vs 15, p = 0.04). The sample size was too small for further subgroup analyses. No other element of the GA was associated with 1-year mortality. As more older adults are considered for HCT, incorporation of a GA to identify coexisting health conditions and functional disability will become increasingly important. This is the first study we are aware of that demonstrates the feasibility of screening patients at the time of HCT evaluation. In this study, we specifically blinded the care team to the to the results of the patients' baseline GA and found that these important markers of overall health and functional status were no different between patients who were selected for transplant and those who were not. Since elements of the GA have been associated with both overall and progression free survival,11, 12 our result highlights an opportunity for the routine use of GA prior to HCT to help select candidates who may experience better outcomes after transplant. In addition, it underscores the geriatrician's role in co-managing patients undergoing HCT: To assist with the implementation and interpretation of routine GA, to intervene on issues that are identified during GA, and to assist in treating age-related complications that arise. This will require further research, including observational studies that incorporate GA assessment results over time to determine the impact of HCT treatments on the recipients' GA scores and randomized clinical trials that randomize whether the baseline GA score is provided to the clinical team to assess the impact this information may have on clinical decision-making and patient mortality and morbidity. Overall, our study highlights both the challenges and opportunities in incorporating a GA as a routine part of the baseline assessment and suggests a role for interdisciplinary management of all older adults undergoing HCT. Dr. Periyakoil and Dr. Johnston contributed to the conception and design of this project, analysis and interpretation of data, and revision of the article. Dr. Sossenheimer contributed to the analysis and interpretation of data, and drafting and revision of the article. Dr. Bharadwaj contributed to the analysis and interpretation of data, and revision of the article. All authors approved the final version for publication. All authors meet the criteria for authorship stated in the Uniform Requirements for Manuscripts Submitted to Biomedical Journals. Dr. Periyakoil's time is funded by the following grants: P30 AG059307/AG/NIA NIH HHS/United States; R01 AG062239/ AG/NIA NIH HHS/United States; U54 MD010724/MD/ NIMHD NIH HHS/United States. Drs. Sossenheimer, Bhadarwaj, and Johnston have no conflicts of interest to disclose. There was no sponsor for this study. This project was supported by a grant from the Stanford Cancer Center Clinical Innovation Fund.

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