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Body Mass Index of Adolescent and Adult
Survivors ofPediatric Acute Lymphoblastic
Leukemia – A Meta-AnalysisGina Nam, BA, BS
Research Assistant
Huntsman Cancer Institute, Cancer Control and Population Sciences
INTRODUCTION• Over 60% of adolescent or adult survivors of pediatric cancer experience at least one late effect in first decade following their diagnosis.
• Late effects include cardiovascular disease, second cancers, and alterations in growth and development.
• A possible late effect is the development of an abnormal body composition (e.g., being overweight or obese) that can potentially increase the risk of developing other chronic health conditions.
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
Series1
3%
57%
78%
92%
Survival Rates
1964
20091987
• ALL is the most common pediatric cancer in the U.S.
• About 3,000 children and adolescents are diagnosed in the U.S. with ALL every year.
Source: American Childhood Cancer Organization
• BMI =
• For adolescents, age-and sex-specific BMI percentile or BMI at final heights are used.
BODY MASS INDEX (BMI)
Adults Adolescents
Underweight ≤ 18.5 kg/m2 ≤ 5th percentile
Normal 18.5 – 25 kg/m2 5th – 85th percentile
Overweight 25 – 30 kg/m2 85th – 95th percentile
Obese ≥ 30 kg/m2 ≥ 95th percentile
EXISTING LITERATURE
• Existing systematic reviews suggest that during childhood, survivors of pediatric ALL have higher BMIs than normative populations.
• However, mixed evidence exists on the risk of overweight/obesity among adolescent and adult survivors of pediatric ALL.
• No meta-analyses on BMI among adolescent and adult survivors of pediatric ALL.
OBJECTIVES
• Conduct a meta-analysis of studies that investigate the BMI of adolescent and adult survivors of pediatric ALL.
• Systematically summarize literature.
• Quantify overall effect size and effect sizes for sex differences.
• Critical assessment of existing gaps in literature.
METHODS
Identified Studies (N=109)
• PRISMA Guidelines.
• Multiple search engines.
• Search phrases: e.g. ALL, body composition, BMI, overweight, adiposity etc.
• Time frame: 1994-2014.
Inclusion Criteria (N=11)
• ALL diagnosed at <21 years of age.
• Age at study ≥16 years.
• BMI at the end of the primary therapy phase.
• Comparison sample or population norms.
• Peer-reviewed. Coding & Analyses
• Coding into Excel by 2 investigators.
• Cross-checked by 2 other researchers.
• Reliability analysis in progress.
• Effect size analysis in Stata and R.
STUDY EFFECT SIZE
Long-Term BMI Health Outcome in Adolescents or Adults
Overweight/Obese Normal
ALL Survivors a b
Controls c d
BMI cutoff points for overweight/obese are based on BMI classification guidelines for adolescents and adults as appropriate.
Primary Effect Size:
Odds Ratio (OR) =
STUDIES (N=11)Author Year Location N ALL Survivors N Controls Stratification
Birkebæk et al 1998 Denmark 33 NA Treatment
Garmey et al 2008 U.S. 1,451 2,167 Sex, Treatment
Geenen et al 2010 Netherlands 141 69 Treatment
Jarfelt et al 2005 Sweden 35 5,439 Sex, Treatment
Meacham et al 2005 U.S. 1,665 40,899 Sex
Ness et al 2007 U.S. 75 NA Sex
Oeffinger et al 2003 U.S. 1,765 2,565 Sex, Age, Treatment
Shaw et al 2000 United Kingdom 33 66 Sex
Tylavsky et al 2010 U.S. 164 NA Age
Veringa et al 2012 Netherlands 68 6,555 Sex, Treatment
Warner et al 2013 U.S. 165 5,410 Sex
FOREST PLOT for ODDS RATIO (N=7*)STUDY OR Plot OR (95% CI) % WEIGHT
*4 studies do not provide enough information to compute OR.
Non U.S. Studies
1.11 (1.04-1.19)
FEMALE SURVIVORS in the U.S. (N=4)
STUDY OR Plot OR (95% CI) % WEIGHT
Overall (I-squared = 74.3%, p = 0.001)
Warner
Oeffinger
Study
Oeffinger
ID
Oeffinger
Garmey
Oeffinger
Meacham
1.32 (1.20, 1.45)
1.14 (0.73, 1.78)
1.29 (0.62, 2.67)
1.76 (1.31, 2.36)
OR (95% CI)
1.67 (1.05, 2.65)
1.72 (1.42, 2.07)
1.32 (0.93, 1.88)
1.04 (0.91, 1.20)
100.00
4.76
1.69
%
9.32
Weight
3.71
22.70
7.26
50.55
1.32 (1.20, 1.45)
1.14 (0.73, 1.78)
1.29 (0.62, 2.67)
1.76 (1.31, 2.36)
OR (95% CI)
1.67 (1.05, 2.65)
1.72 (1.42, 2.07)
1.32 (0.93, 1.88)
1.04 (0.91, 1.20)
100.00
4.76
1.69
%
9.32
Weight
3.71
22.70
7.26
50.55
10 1 3
MALE SURVIVORS in the U.S. (N=4)
STUDY OR Plot OR (95% CI) % WEIGHT
Overall (I-squared = 77.5%, p = 0.000)
Oeffinger
Warner
Oeffinger
Meacham
Oeffinger
ID
Study
Garmey
Oeffinger
0.93 (0.85, 1.03)
1.46 (1.11, 1.92)
1.29 (0.85, 1.95)
0.80 (0.49, 1.29)
0.76 (0.66, 0.87)
2.60 (0.97, 6.97)
OR (95% CI)
1.03 (0.84, 1.26)
0.89 (0.63, 1.26)
100.00
9.99
4.56
4.19
51.90
0.70
Weight
%
20.84
7.82
0.93 (0.85, 1.03)
1.46 (1.11, 1.92)
1.29 (0.85, 1.95)
0.80 (0.49, 1.29)
0.76 (0.66, 0.87)
2.60 (0.97, 6.97)
OR (95% CI)
1.03 (0.84, 1.26)
0.89 (0.63, 1.26)
100.00
9.99
4.56
4.19
51.90
0.70
Weight
%
20.84
7.82
10 1 7
GAPS IN EXISTING LITERATURE• Identified only 11 quality studies, of which 6 were conducted in the U.S.
• Reporting standards not unique. • 9 studies report BMI proportions.• 7 studies report mean BMI.• 2 studies report BMI Z-score relative to reference values.
• Missing information on a host of important variables.• Cancer relapse.• Detailed treatment and BMI.• Family medical history.• Sample size of controls.
CONCLUSIONS/RECOMMENDATIONS• Overall effect size for survivors in the U.S.
• OR= 1.11; 95% CI= 1.04-1.19.
• Female survivors (OR=1.32; 95% CI=1.20-1.45 ) may be overweight/obese at greater numbers than male survivors (OR=0.93; 95% CI=0.85-1.03).
• Recommendations:• Long-term health management programs for adolescent and
adult survivors of pediatric ALL.
• More emphasis on addressing weight-related health behaviors for female survivors of pediatric ALL.
• Standardized reporting of results for robust meta-analyses.
LIMITATIONS
• BMI is an indirect measurement of body fat, and does not reflect changes in muscle mass or changes that occur with age in adulthood.
• With the limited number of available studies, characteristics of control population, treatment etc. are inconclusive.
Thank [email protected]
Collaborators: Richard Nelson, PhD Sapna Kaul, PhD, MA Yelena Wu, PhD Anne Kirchhoff, PhD, MPH
Funded by the Center for Children’s Cancer Research at
the Huntsman Cancer Institute
