Overweight as a Prognostic Factor in Children With Acute Lymphoblastic Leukemia

Gelelete, Cristina Berbert; Pereira, Stefânia Araújo; Azevedo, Alexandro Barbosa de; Thiago, Leandro S.; Mundim, Mariana; Land, Marcelo Gerardin Poirot; Costa, Edja Maria Melo de Brito

doi:10.1038/oby.2011.195

Cited by 65 publications

(68 citation statements)

References 16 publications

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“…[5][6][7][8][9][10] Furthermore, although Butturini et al 5 described an association between obesity at diagnosis and survival in children treated for ALL on Children's Oncology Group (COG) protocols, reports from other consortia have not supported this observation. 9,11 Patients underweight at diagnosis in developing countries have been found to have inferior outcomes, 12,13 but this too has not been replicated in studies of patients treated in developed countries.…”

Section: Introductionmentioning

confidence: 70%

Impact on Survival and Toxicity by Duration of Weight Extremes During Treatment for Pediatric Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

Orgel

Sposto

Malvar

et al. 2014

JCO

143

141

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Purpose Previous studies regarding the influence of weight on event-free survival (EFS) and treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL) considered only weight at diagnosis. Inasmuch as weight varies substantially over treatment, we hypothesized its impact on EFS is instead determined by cumulative time spent at an extreme weight during therapy and on TRT by weight at the time of toxicity. Patients and Methods In a cohort of 2,008 children treated for high-risk ALL in Children's Oncology Group study CCG-1961, we determined the effect on EFS of cumulative time receiving therapy at an extreme weight (either obese or underweight) between end of induction and start of maintenance therapy. We also evaluated the association between weight category and incidence and patterns of TRT during 13,946 treatment courses. Results Being obese or underweight at diagnosis and for ≥ 50% of the time between end of induction and start of maintenance therapy resulted in inferior EFS (hazard ratios, 1.43 and 2.30, respectively; global P < .001). Normalization of weight during that period resulted in mitigation of this risk comparable to never being obese or underweight. Obese or underweight status at start of each treatment course was significantly associated with specific patterns of TRT. Conclusion Influence of weight extremes on EFS and TRT is not set at diagnosis as previously reported but is moderated by subsequent weight status during intensive postinduction treatment phases. These observations suggest that weight is a potentially addressable risk factor to improve EFS and morbidity in pediatric ALL.

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Section: Introductionmentioning

confidence: 70%

Impact on Survival and Toxicity by Duration of Weight Extremes During Treatment for Pediatric Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

Orgel

Sposto

Malvar

et al. 2014

JCO

143

141

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“…Previous studies suggested that being underweight or overweight is associated with a compromised outcome in children with ALL, 4,[9][10][11][12]14 indicating that "extremes" matter. This has also been shown in pediatric acute myeloid leukemia.…”

Section: Discussionmentioning

confidence: 99%

“…3 Previous studies in pediatric ALL showed contradictory results, i.e. some studies show that weight at diagnosis does not influence survival, while others suggest that being underweight or overweight at diagnosis of ALL has an influence on survival [4][5][6][7][8][9][10][11][12][13][14] (Table 1). Body composition changes extremely during the treatment of pediatric ALL due to the use of corticosteroids, 15,16 but also due to other factors such as the catabolic effect of the disease itself, stress, 17 nutritional changes and impaired exercise capacity.…”

Section: Introductionmentioning

confidence: 99%

The negative impact of being underweight and weight loss on survival of children with acute lymphoblastic leukemia

et al. 2014

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Correspondence: m.vandenheuvel@erasmusmc.nlBody mass index and change in body mass index during treatment may influence treatment outcome of pediatric patients with acute lymphoblastic leukemia. However, previous studies in pediatric acute lymphoblastic leukemia reported contradictory results. We prospectively collected data on body composition from a cohort of newly diagnosed Dutch pediatric patients with acute lymphoblastic leukemia (n=762, age 2-17 years). Patients were treated from 1997-2004 and the median follow-up was 9 years (range, 0-10). Body mass index at diagnosis was expressed as age-and gender-matched standard deviation scores and on the basis of these scores the patients were categorized as being underweight, of normal weight or overweight. Multivariate analyses showed that patients who were underweight (8%) had a higher risk of relapse [hazard ratio: 1.88, 95% confidence interval (1.13-3.13)], but similar overall survival and event-free survival as patients who had a normal weight or who were overweight. Patients with loss of body mass index during the first 32 weeks of treatment had a similar risk of relapse and eventfree survival, but decreased overall survival [hazard ratio: 2.10, 95% confidence interval (1.14-3.87)] compared to patients without a loss of body mass index. In addition, dual X-ray absorptiometry scans were performed in a nested, single-center cohort. Data from these scans revealed that a loss of body mass consisted mainly of a loss of lean body mass, while there was a gain in the percentage of fat. In conclusion, being underweight at diagnosis is a risk factor for relapse, and a decrease in body mass index early during treatment is associated with decreased survival. In addition, loss of body mass during treatment seems to consist mainly of a loss of lean body mass. This study was approved by the Medical Ethical Committee in 1996 (trial number NTR460/SNWLK-ALL-9). The negative impact of being underweight and weight loss on survival of children with acute lymphoblastic leukemia ABSTRACT Methods Study populationThis study included newly diagnosed pediatric ALL patients, aged 2-17 years, treated according to the Dutch Childhood Oncology Group (DCOG) -ALL9 protocol, between January 1997 and November 2004 in seven pediatric oncology centers in the Netherlands. 21 The patients were stratified at diagnosis into nonhigh-risk and high-risk treatment groups as previously described.21

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“…Subsequently in 2007, the first report on pediatric ALL described poorer event-free survival (EFS) in a large cohort of obese children compared with those who were nonobese (7). After these 2 landmark studies in pediatric leukemia, multiple analyses from international consortia have since described inconsistent associations between obesity and leukemia survival (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), raising uncertainty as to whether such a relation exists and, if so, to what extent.…”

Section: Introductionmentioning

confidence: 99%

Association of body mass index and survival in pediatric leukemia: a meta-analysis

Orgel

Genkinger²,

Aggarwal

et al. 2016

The American Journal of Clinical Nutrition

122

101

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Background: Obesity is a worldwide epidemic in children and adolescents. Adult cohort studies have reported an association between higher body mass index (BMI) and increased leukemiarelated mortality; whether a similar effect exists in childhood leukemia remains controversial. Objective: We conducted a meta-analysis to determine whether a higher BMI at diagnosis of pediatric acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) is associated with worse event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR). Design: We searched 4 electronic databases from inception through March 2015 without language restriction and included studies in pediatric ALL or AML (0-21 y of age) reporting BMI as a predictor of survival or relapse. Higher BMI, defined as obese ($95%) or overweight/obese ($85%), was compared with lower BMI [nonoverweight/obese (,85%)]. Summary risk estimates for EFS, OS, and CIR (ALL only) were calculated with random-or fixed-effects models according to tests for between-study heterogeneity. Results: Of 4690 reports identified, 107 full-text articles were evaluated, with 2 additional articles identified via review of citations; 11 articles were eligible for inclusion in this meta-analysis. In ALL, we observed poorer EFS in children with a higher BMI (RR: 1.35; 95% CI: 1.20, 1.51) than in those at a lower BMI. A higher BMI was associated with significantly increased mortality (RR: 1.31; 95% CI: 1.09, 1.58) and a statistically nonsignificant trend toward greater risk of relapse (RR: 1.17; 95% CI: 0.99, 1.38) compared with a lower BMI. In AML, a higher BMI was significantly associated with poorer EFS and OS (RR: 1.36; 95% CI: 1.16, 1.60 and RR: 1.56; 95% CI: 1.32, 1.86, respectively) than was a lower BMI. Conclusion: Higher BMI at diagnosis is associated with poorer survival in children with pediatric ALL or AML.Am J Clin Nutr 2016;103:808-17.

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Overweight as a Prognostic Factor in Children With Acute Lymphoblastic Leukemia

Cited by 65 publications

References 16 publications

Impact on Survival and Toxicity by Duration of Weight Extremes During Treatment for Pediatric Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

Impact on Survival and Toxicity by Duration of Weight Extremes During Treatment for Pediatric Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

The negative impact of being underweight and weight loss on survival of children with acute lymphoblastic leukemia

Association of body mass index and survival in pediatric leukemia: a meta-analysis

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