Division of Hematology and Medical Oncology and Mayo Clinic Cancer Center, Mayo Clinic, Jacksonville, Florida, USA.
Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) Biostatistics Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Cancer. 2023 Aug 15;129(16):2479-2490. doi: 10.1002/cncr.34807. Epub 2023 Apr 25.
Obesity (body mass index [BMI] ≥30 kg/m ) is an important epidemiological risk factor for developing acute myeloid leukemia (AML). Therefore, the authors studied the association of obesity with clinical and genetic phenotype and its impact on outcome in adults with AML.
The authors analyzed BMI in 1088 adults who were receiving intensive remission induction and consolidation therapy in two prospective, randomized therapeutic clinical trials of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network: E1900 (ClinicalTrials.gov identifier NCT00049517; patients younger than 60 years) and E3999 (ClinicalTrials.gov identifier NCT00046930; patients aged 60 years or older).
Obesity was prevalent at diagnosis (33%) and, compared with nonobesity, was associated with intermediate-risk cytogenetics group (p = .008), poorer performance status (p = .01), and a trend toward older age (p = .06). Obesity was not associated with somatic mutations among a selected 18-gene panel that was tested in a subset of younger patients. Obesity was not associated with clinical outcome (including complete remission, early death, or overall survival), and the authors did not identify any patient subgroup that had inferior outcomes based on BMI. Obese patients were significantly more likely to receive <90% of the intended daunorubicin dose despite protocol specification, particularly in the E1900 high-dose (90 mg/m ) daunorubicin arm (p = .002); however, this did not correlate with inferior overall survival on multivariate analysis (hazard ratio, 1.39; 95% confidence interval, 0.90-2.13; p = .14).
Obesity is associated with unique clinical and disease-related phenotypic features in AML and may influence physician treatment decisions regarding daunorubicin dosing. However, the current study demonstrates that obesity is not a factor in survival, and strict adherence to body surface area-based dosing is not necessary because dose adjustments do not affect outcomes.
肥胖(体重指数 [BMI]≥30kg/m )是发生急性髓系白血病(AML)的重要流行病学风险因素。因此,作者研究了肥胖与成人 AML 临床和遗传表型的相关性及其对结局的影响。
作者分析了在两项东部肿瘤协作组-美国放射肿瘤学会影像学网络前瞻性、随机治疗临床试验中接受强化缓解诱导和巩固治疗的 1088 例成年人的 BMI,E1900 试验(ClinicalTrials.gov 标识符 NCT00049517;患者年龄<60 岁)和 E3999 试验(ClinicalTrials.gov 标识符 NCT00046930;患者年龄≥60 岁)。
诊断时肥胖较为常见(33%),与非肥胖者相比,肥胖者更易出现中危细胞遗传学分组(p=0.008)、较差的体能状态(p=0.01)和年龄偏大趋势(p=0.06)。在年轻患者亚组中进行了选定的 18 基因检测,肥胖与其中的体细胞突变无关。肥胖与临床结局(包括完全缓解、早期死亡或总生存)无关,作者未发现任何基于 BMI 的亚组患者预后更差。尽管方案规定,肥胖患者接受的达柔比星剂量明显低于预期剂量(90%),尤其是在 E1900 高剂量(90mg/m )达柔比星组(p=0.002);但在多变量分析中,这与总生存较差无关(危险比,1.39;95%置信区间,0.90-2.13;p=0.14)。
肥胖与 AML 独特的临床和疾病相关表型特征相关,可能影响医生对达柔比星剂量的治疗决策。然而,本研究表明肥胖不是生存的因素,且不必严格遵循基于体表面积的剂量,因为剂量调整不会影响结局。