Overweight or Obesity and Outcomes in Children With Acute Lymphoblastic Leukemia

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.

Figure 1.. Mean Body Mass Index (BMI) z Score Trajectories From Diagnosis to End of Treatment (EOT) by Demographic and Clinical Characteristics

Paired t test analyses were performed to compare the mean BMI z scores at diagnosis with those at end of induction (EOI), continuation (CON), and EOT. BMI is calculated as weight in kilograms divided by height in meters squared. ^aP ≤ .05. ^bP < .001.

Figure 2.. Overall Survival, Cumulative Incidence of Relapse, and Event-Free Survival From End of Treatment (EOT) to Post Treatment by Duration of Overweight (OW) or Obesity (OB)

BMI indicates body mass index.

Figure 3.. Overall Survival, Cumulative Incidence of Relapse, and Event-Free Survival From End of Treatment to Post Treatment by Number of Time Points With Overweight (OW) or Obesity (OB)

Kaplan-Meier survival curves were generated comparing patients with an underweight or normal weight classification at all time points with patients with underweight or normal weight at diagnosis who developed OW or OB at 1 or more time point and patients with OW or OB at all 3 time points. Dx indicates diagnosis.