A high BMI is a risk factor in younger patients with de novo acute myelogenous leukemia

Abstract

Overweight and obese patients have an increased risk to develop several malignancies and, additionally, body mass index (BMI) impacts on outcome in several solid tumors. However, little is known for AML. We analyzed a cohort of 3526 patients with AML treated in three prospective multicenter trials within the German Study Alliance Leukemia. In multivariate analyses, we identified BMI as an independent risk factor for both DFS (HR 1.014, P = 0.0217) and OS (HR 1.015, P < 0.0036). Interestingly, overweight and obesity seemed to be a risk factor predominantly in patients with de novo AML younger than 65 yr with intermediate risk and adverse cytogenetics. Overweight with a BMI ≥25 kg/m² best discriminated the worse outcome and led to an absolute reduction in long-term survival of 5-7% in the group of all younger patients (3-yr OS 39.9% vs. 47.3%; 10-yr OS 28.7% vs. 33.8%, P = 0.0002). Additionally, response to induction therapy was significantly reduced in these patients (76.9% vs. 82.8%, P < 0.0001). Thus, in younger patients with de novo AML, overweight and obesity are risk factors for impaired response to induction therapy, DFS and OS. This effect is, in part but not fully, explained by dose reduction such as dose-capping at a body surface area of 2 m².

Impact of body‐surface area on patients’ outcome in younger adults with acute myeloid leukemia

“…A slight—but not significant—decrease in CR rate after induction therapy along with non‐significant increases in relapse incidence and non‐relapse mortality was observed in the very high BSA group. Noteworthy, cytogenetic risk groups and molecular status were well balanced between the different BMI and BSA groups, suggesting that leukemic biological abnormalities do not appear responsible for this poor outcome . A specific pharmacokinetics in the very high BSA group may take part in this adverse outcome.…”

“…Dose capping—as a priori prescribed by physicians—may also participate in this poor outcome . The OS of patients with full‐dose induction (n=20) was slightly—although not significantly—superior to that of patients with capped doses (n=31).…”

“…Several groups have addressed the issue of obese young patients with AML, and most studies did not find any significant impact of obesity or high BSA on outcome . One study showed better survival outcomes for obese patients while another series showed lower survival for patients with BMI>25 kg/m 2 . The vast majority of these studies targeted the obese (BMI≥30 kg/m 2 ) or high BSA (>2 m 2 ) population as a whole and did not separate extreme anthropomorphic cases (eg, BSA≥2.15 m 2 or BMI≥35 kg/m 2 ).…”

“…7,8,[11][12][13][18][19][20] One study showed better survival outcomes for obese patients 8 while another series showed lower survival for patients with BMI>25 kg/m 2 . 21 The vast majority of these studies targeted the obese (BMI≥30 kg/m 2 ) or high BSA (>2 m 2 ) population as a whole and did not separate extreme anthropomorphic cases (eg, BSA≥2.15 m 2 or BMI≥35 kg/m 2 ). In accordance with the majority of these studies, we did not find any adverse outcome in patients with BMI≥30 kg/m 2 or BSA>2 m 2 .…”

Incidence, Survival, and Risk Factors for Adults with Acute Myeloid Leukemia Not Otherwise Specified and Acute Myeloid Leukemia with Recurrent Genetic Abnormalities: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database, 2001–2013

“…Third, we did not examine the impact of complex biological factors, such as body mass index, on risk of death due to WHO AML-NOS or AML-RGA. Obesity has recently been shown to be associated with poor outcomes among young patients in Germany [39]. …”