Geriatric assessment in older patients with acute myeloid leukemia: A retrospective study of associated treatment and outcomes
Introduction
Acute myeloid leukemia (AML) is a disease of older adults whose incidence will increase dramatically in coming decades due to population aging [1]. AML patients over age 65 have much worse prognosis than younger patients, with a five-year disease-specific survival of only 5% [2]. These poor outcomes are due to a combination of age-related changes in disease biology and clinical factors such as decreased physiologic reserve, functional impairment and frailty [3], [4], [5]. Previous work has identified age, performance status, comorbidity, and cytogenetic risk group as important prognostic factors in older patients with AML [6]. However, few studies have explored the relationship between geriatric assessment and AML outcomes.
Comprehensive geriatric assessment (CGA) is a systematic method of identifying multiple predictors of morbidity and mortality in older adults that may impact cancer treatment and is recommended for older cancer patients by NCCN guidelines [7]. This recommendation was in part based on a multicenter study demonstrating that a self-administered geriatric assessment identified important prognostic factors in cancer patients [8]. A geriatric evaluation includes assessment of multiple domains including comorbidity and physical, cognitive and social function. The feasibility of performing a modified CGA in older patients with AML has been demonstrated, but it is not yet known how this information predicts outcomes [9].
Careful assessment of the potential benefits and risks of therapy is particularly vital in AML, as intensive chemotherapy with cytarabine and an anthracycline is the only treatment that gives hope of long-term survival. Response to induction is poor among older adults and toxicity is substantially higher than in younger individuals, but selected patients can achieve remission and cure [10], [11], [12]. Patients who are not candidates for induction may benefit from non-intensive treatments such as hypomethylating agents, and some are best served by purely palliative approaches [13], [14]. However, it can be difficult to predict which older patients will benefit from chemotherapy using routine clinical and biological factors alone. Growing evidence suggests that measures of comorbidity and functional status may also be valuable prognostic factors in elderly patients with AML [15], [16], [17], [18]. We utilized prospectively collected quality of life data to evaluate the utility of geriatric factors as predictors of survival in older patients with AML across varying treatment intensities.
Section snippets
Data collection
We performed a retrospective cohort study of consecutive patients ≥65 years of age that presented to Dana-Farber Cancer Institute (DFCI) between 2006 and 2011 for evaluation of a new diagnosis of AML. At the DFCI, all new patients with hematologic malignancies are asked to participate in a research protocol that involves a baseline questionnaire and prospective collection of clinical data into the Cancer Research Information System (CRIS) database. CRIS includes information collected by trained
Results
Between 2006 and 2011, 368 patients 65 and older presented to the DFCI with a diagnosis of AML. Of these, 163 (44.3%) did not complete the new patient survey prior to hospitalization for AML, 62 (16.8%) received previous chemotherapy for AML, and 42 were missing information on key variables, leaving 101 patients for the analysis. Baseline characteristics of the cohort are listed in Table 1. Overall, the cohort was white (98%), had a performance status ≤1 (79.3%), and had ≤1 comorbidity (72.4%).
Discussion
In this retrospective study of older patients with AML, we found that baseline geriatric assessment variables added valuable prognostic information to conventional clinical and pathological predictors of mortality. The model that best predicted survival in our cohort included a disease-specific comorbidity score and self-reported measures of strenuous activity and pain in addition to cytogenetic risk group. Geriatric assessment variables remained independent predictors of mortality even among
Conflict of interest statement
The authors report no conflicts of interest or disclosures that could inappropriately influence their work on this project. Dr. Richard M Stone has served in a Consultant or Advisory Role for Genzyme© and has received investigator-initiated research funding from Novartis©. Dr. Daniel J DeAngelo has served in a consultant or advisory role for Novartis©.
Acknowledgements
Funding source: Dr. Driver is funded by a Veterans’ Administration Career Development award. Alexander Sherman is funded by an American Federation for Aging Research Grant #1T35AG038027-02.
Author contributions: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data (AES, GM, KRF, DJD, GAA, DS, MW, RMS, JAD), (2) drafting the article or revising it critically for important intellectual content (AES, GM, KRF, DJD, GAA, DS, MW, RMS, JAD), (3)
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2021, BloodCitation Excerpt :Still, future improvements in comorbidity assessment for AML to capture patients with more severe organ dysfunction could further improve stratifications for treatment outcomes. Another important measure of patient vulnerability is geriatric assessment including measures of frailty, physical, and cognitive function, which have been shown to predict survival.27-29 Accounting for comorbidities and geriatric assessment in the current study allowed for more informed and objective treatment comparisons.