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超重或肥胖与急性淋巴细胞白血病患儿的预后

Overweight or Obesity and Outcomes in Children With Acute Lymphoblastic Leukemia.

作者信息

Ladas Elena J, Sheng Haiyang, Athale Uma H, Asselin Barbara L, Clavell Luis A, Cole Peter D, Flamand Yael, Leclerc Jean-Marie, Laverdiere Caroline, Michon Bruno, Sallan Stephen E, Silverman Lewis B, Welch Jennifer J G, Yao Song, Kelly Kara M

机构信息

Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University Irving Medical Center, New York, New York.

Department of Cancer Prevention, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

出版信息

JAMA Netw Open. 2025 May 1;8(5):e259952. doi: 10.1001/jamanetworkopen.2025.9952.

Abstract

IMPORTANCE

There are conflicting data on the association of overweight or obesity with clinical outcomes in childhood acute lymphoblastic leukemia (ALL). The duration of exposure to overweight or obesity may be a better indicator of the risk of poorer outcomes.

OBJECTIVE

To determine the association of the duration of overweight or obesity with treatment-related toxic effects, minimal residual disease, relapse, and survival in childhood ALL.

DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, fluctuations in z scores of body mass index (BMI) for age from diagnosis to the end of treatment (EOT) were examined in 794 children registered on a Dana Farber Cancer Institute ALL Consortium protocol from May 31, 2005, to December 15, 2011. Height and weight were abstracted from the medical record for classification of BMI z scores at diagnosis through EOT and into survivorship. Data were analyzed from July 1 to 31, 2024.

MAIN OUTCOMES AND MEASURES

The duration of overweight or obesity was defined as having overweight or obesity at 2 or more time points and compared with having overweight or obesity at no more than 1 time point. Kaplan-Meier survival curves were generated to examine association of overweight or obesity with overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse.

RESULTS

Among the 794 patients included in the analysis, the mean age at diagnosis was 6.7 (range, 1.0-17.9) years, with 441 (55.5%) being male, 136 (17.1%) Hispanic, and 553 (69.6%) non-Hispanic. The prevalence of overweight or obesity increased from 234 of 793 (29.5%) at diagnosis to 346 of 715 (48.4%) by EOT. Having overweight or obesity at baseline or developing overweight or obesity during induction was not associated with treatment-related toxic effects or higher minimal residual disease. Children with overweight or obesity at 2 or more time points experienced inferior OS (3-year OS, 93.8% vs 98.0%; P = .01), increased relapse (3-year relapse rate, 10.5% vs 5.8%; P = .02), and lower EFS (3-year EFS, 89.0% vs 93.7%; P = .02), compared with children with overweight or obesity at no more than 1 time point. Multivariable Cox proportional hazards regression models revealed an association between increased risk of death (hazard ratio [HR], 3.49; 95% CI, 1.28-9.51; P = .01) and relapse (HR, 1.92; 95% CI, 1.07-3.46; P = .03) among children with overweight or obesity at 2 or more time points.

CONCLUSIONS AND RELEVANCE

In this prospective cohort study of children with ALL, longer duration of overweight or obesity was associated with lower OS and EFS and higher rates of relapse, underscoring the need for interventions targeting overweight or obesity during treatment of children with ALL.

摘要

重要性

关于超重或肥胖与儿童急性淋巴细胞白血病(ALL)临床结局之间的关联,存在相互矛盾的数据。超重或肥胖的暴露持续时间可能是预后较差风险的更好指标。

目的

确定超重或肥胖的持续时间与儿童ALL治疗相关毒性、微小残留病、复发和生存之间的关联。

设计、设置和参与者:在这项前瞻性队列研究中,对2005年5月31日至2011年12月15日在达纳-法伯癌症研究所ALL联盟方案登记的794名儿童,检查了从诊断到治疗结束(EOT)年龄别体重指数(BMI)z评分的波动情况。从病历中提取身高和体重,用于诊断至EOT以及生存期间BMI z评分的分类。数据于2024年7月1日至31日进行分析。

主要结局和测量指标

超重或肥胖的持续时间定义为在两个或更多时间点存在超重或肥胖,并与不超过一个时间点存在超重或肥胖进行比较。生成Kaplan-Meier生存曲线,以检查超重或肥胖与总生存(OS)、无事件生存(EFS)和复发累积发生率之间的关联。

结果

纳入分析的794例患者中,诊断时的平均年龄为6.7岁(范围1.0 - 17.9岁),男性441例(55.5%),西班牙裔136例(17.1%),非西班牙裔553例(69.6%)。超重或肥胖的患病率从诊断时793例中的234例(29.5%)增至EOT时715例中的346例(48.4%)。基线时超重或肥胖或在诱导期出现超重或肥胖与治疗相关毒性或更高的微小残留病无关。与不超过一个时间点存在超重或肥胖的儿童相比,在两个或更多时间点存在超重或肥胖的儿童OS较差(3年OS,93.8%对98.0%;P = 0.01),复发增加(3年复发率,10.5%对5.8%;P = 0.02),EFS较低(3年EFS,89.0%对93.7%;P = 0.02)。多变量Cox比例风险回归模型显示,在两个或更多时间点存在超重或肥胖的儿童中,死亡风险增加(风险比[HR],3.49;95%置信区间[CI],1.28 - 9.51;P = 0.01)和复发风险增加(HR,1.92;95% CI,1.07 - 3.46;P = 0.03)之间存在关联。

结论和相关性

在这项针对ALL儿童的前瞻性队列研究中,超重或肥胖的持续时间较长与较低的OS和EFS以及较高的复发率相关,强调在ALL儿童治疗期间针对超重或肥胖进行干预的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f123/12079296/c21583e0fd17/jamanetwopen-e259952-g001.jpg

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