Abstract
Acute Myeloid Leukemia (AML) is more common among patients over the age of 60, who also historically have a poorer prognosis. It is unclear which patients will benefit most from intensive chemotherapy; prognostic factors have been identified to risk-stratify these patients, but tend to consider characteristics specific to the disease such as cytogenetics [Lancet 2010; 376: 2000–08], and may not account for patient comorbidities that preceded the diagnosis of AML. Increased body mass index (BMI) has been associated with an increased incidence of various malignancies, including AML [The Oncologist 2010; 15: 1083–1101], and is increasingly prevalent among the general population. We sought to determine whether patient BMI at time of AML diagnosis is related to overall survival among patients older than age 60.
We performed a retrospective chart review of all patients diagnosed at Massachusetts General Hospital with records available in the electronic medical record between January 1, 1992 and May 1, 2011. Patients were identified using billing codes and pathology records and underwent chart review to confirm a diagnosis of AML. Patients were included in this review if they had a pathologically-confirmed new diagnosis of AML, were older than age 60 at the time of diagnosis, and were given cytarabine-based induction chemotherapy. We collected past medical history, presenting labs, patient cytopathology, weight, and height at diagnosis. Overall survival (OS) was estimated using the Kaplan-Meier method, with 95% confidence intervals calculated using Greenwood's formula. We then performed a stepwise multivariable Cox regression analysis, pre-specifying that a variable had to be significant at the 0.3 level before it could be entered into the model, while a variable in the model had to be significant at the 0.05 level for it to remain in the model.
We identified 152 patients with AML diagnosed after the age of 60. The median age was 68 years (range 60–87); 54% of patients were male, and 86% were white. Patient disease was identified as de novo in 50%, and secondary in 50%. Cytogenetics, when available (86.2% of patients), were most commonly normal (37.5%) or poor risk (34.2%); only 1.3% of patients were good risk. The median OS for all patients was 269 days (95% CI 217–323). The 60 day OS for all patients was 83% (95% CI 77–89%). Using the log-rank test to perform a univariate analysis, worsened OS was associated with increased age (P=0.024); body mass index (BMI) < 27, the median BMI in our cohort, (P=0.011); presence of coronary artery disease (CAD) (P=0.042); and with cytogenetics (P=0.013). The multivariable analysis of the Cox proportional-hazards model found that the hazard rate for death was increased with older age (HR 1.53, P=0.027, 95% CI 1.05–2.24), lower BMI < 27 (HR 1.93, P=0.002, 95% CI 1.28–2.92) and cytogenetics (P<0.05). After multivariable analysis we did not find a significant association between OS and CAD, diabetes, gender, race, de novo vs. secondary disease, or presenting hematocrit, sodium, or total bilirubin.
Patients over the age of 60 with a new diagnosis of AML carry a poor prognosis; comorbid disease at the time of presentation may assist a clinician in risk stratification of this age group. Intriguingly, BMI greater than or equal to 27 was associated with improved OS among patients older than 60 treated at our institution. Additional studies will be necessary to determine the causal factors of worse survival in patients older than age 60 who have normal BMI compared to obese patients and to identify approaches that will ameliorate these poorer outcomes in this population.
No relevant conflicts of interest to declare.
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Author notes
Asterisk with author names denotes non-ASH members.