Early mortality and survival in older adults with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a disease of older adults [1] and has a median age of 68 years at the time of diagnosis. The management of AML in older patients (>60 years) is far from optimal and often associated with poor outcomes. Over half of the older patients do not receive initial chemotherapy [1,2], remission rate is lower than in younger patients and lasts shorter duration, and long term survival is dismal. For example, 5-year survival is over 50% for patients aged 15–24 years that drops steadily to 13% for patients between 60 and 69 years of age and 3% for those aged 70–79 years [3]. Functional status varies widely even in older patients with similar biological age and affects outcome. For instance, data from the Southwest Oncology Group trials demonstrated that the early mortality at 1 month for patients older than 75 years is 14% with Eastern Cooperative Oncology Group performance score of 0 versus 82% for a score of 3 [4]. Higher incidence of comorbidities negatively affects outcomes [1]. This is reflected by a higher 8-week mortality (30 vs 19%) in patients with a higher modified Charlson Comorbidity Index of >1 versus ≤ 1, respectively [5]. Comorbidities may lead to poor tolerance of chemotherapy, enhanced toxicity, particularly following intensive chemotherapy and a lower rate of complete response. Malnutrition, decreased immunity with increased susceptibility to infection, cognitive decline and social isolation pose increased risk of toxicity from chemotherapy. Older adults have higher rates of multidrug resistance compared with the younger patients (57 vs 33%) [4]. The proportion with unfavorable cytogenetics increases with age, whereas translocation associated with favorable response drops. AML in younger patients may result from a limited number of mutational events restricting diversity of leukemic subclones and leaving many cell functions intact including mechanism of apoptosis. AML in the older patients, however, may arise due to string of mutational events producing multiple leukemic subclones giving rise to chemoresistance. Patients with pre-existing myelodysplastic or myeloproliferative disorders (i.e., secondary AML) have higher probability of harboring poor cytogenetics, which translates to poor survival. Also, the presence of secondary AML type mutations, commonly observed in older patients, is associated with poor chances of achieving remission and long-term disease control [6]. Overall care of older patients with AML may improve with refined risk-stratification and personalized therapy based on the principles of geriatric medicine. For example, careful assessment of comorbid conditions is vital in older patients. Comprehensive geriatric assessment is also valuable in determining tolerance to various intensities of chemotherapy. Geriatric assessment evaluates multiple health domains including comorbidities, polypharmacy, cognitive, nutritional, psychological, functional and social status, and can predict tolerance of chemotherapy better than chronological age and performance status alone [7–9]. A multidisciplinary leukemia care team may perform a comprehensive geriatric assessment to identify and address cognitive impairment, depression and various geriatric syndromes. Physical, psychological and neurocognitive prehabilitation may improve quality of life, chemotherapy tolerance and mortality. It should be stressed that such assessment should be done on an ongoing basis as clinical conditions could change over time.