Body Mass Index of Adolescent and Adult Survivors of Pediatric Acute Lymphoblastic Leukemia – A...

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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 you!gina.nam@hci.utah.edu

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