Body Mass Index at Pediatric Leukemia Diagnosis and the Risks of Relapse and Mortality: Findings from a Single Institution and Meta-analysis.

High body mass index (BMI) is associated with relapse of certain adult cancers, but limited knowledge exists on its association with pediatric leukemia relapse. We evaluated the association between overweight/obesity (BMI ≥ 85th percentile) at pediatric leukemia diagnosis and relapse or mortality. A meta-analysis combining our findings with those of previous studies was also performed. The study included 181 pediatric leukemia patients. Sporadic missing data were multiply imputed, and hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazard. Age- and sex-adjusted analysis for patients ≥10 years showed a trend towards increased risk of relapse for overweight/obese patients (HR = 2.89, 95% CI = 0.89-9.36, p=0.08) that was not evident among children<10 years (HR = 0.52, 95% CI = 0.08-3.54, p=0.49). We observed a statistically significant association between mortality and obesity status in unadjusted models (imputed: HR = 2.54, 95% CI = 1.15-5.60, p=0.021; complete set: HR = 2.72, 95% CI = 1.26-5.91, p=0.011) that was not statistically significant in both age- and sex-adjusted and multivariable adjusted analyses. The pooled estimate of our finding and previous studies showed an association between overweight/obese and increased risk of mortality for ALL (HR = 1.39, 95% CI = 1.16-1.46) and AML (HR = 1.64, 95% CI = 1.32-2.04). Although our study did not observe statistically significant associations due to a small sample size, the meta-analyses revealed an increased risk of mortality for overweight/obese patients. The findings of our study suggest an association of obesity status with relapse in children ≥10 years. However, our study was based on a small sample size from a single institution, and this association needs to be investigated in larger, multicenter studies.

Association between body mass index at diagnosis and pediatric leukemia mortality and relapse: a systematic review and meta-analysis.

Obesity is a risk factor for mortality and relapse of certain cancers. However, existing evidence for pediatric leukemia is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the association between obesity at diagnosis and pediatric acute leukemia mortality and relapse. This study systematically searched MEDLINE and EMBASE from inception to February 5, 2015. Random-effect models were used to generate pooled estimates of study-specific hazard ratios (HR) and 95% confidence intervals (CI). Eleven studies were included. An increased risk of mortality with a high BMI at diagnosis was observed (overall survival: HR=1.30, 95% CI=1.16-1.46 and event-free survival: HR=1.46, 95% CI=1.29-1.64). Only two studies reported HR for relapse; one reported a reduced risk, while the other reported an increased risk. A high BMI at diagnosis is associated with poor overall and event-free survival among pediatric acute leukemia patients. Targeted therapeutic approaches for obese pediatric leukemia patients may potentially improve survival outcomes.

Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial.

IMPORTANCE: Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results. OBJECTIVE: To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Multicenter (26 pediatric endocrinology clinics), double-blind, placebo-controlled randomized clinical trial involving 140 adolescents aged 12.1 to 19.6 years (mean [SD] 15.3 [1.7] years) with mean type 1 diabetes duration 7.0 (3.3) years, mean body mass index (BMI) 94th (4) percentile, mean total daily insulin 1.1 (0.2) U/kg, and mean HbA1c 8.8% (0.7%). INTERVENTIONS: Randomization to receive metformin (n = 71) (≤2000 mg/d) or placebo (n = 69). MAIN OUTCOMES AND MEASURES: Primary outcome was change in HbA1c from baseline to 26 weeks adjusted for baseline HbA1c. Secondary outcomes included change in blinded continuous glucose monitor indices, total daily insulin, BMI, waist circumference, body composition, blood pressure, and lipids. RESULTS: Between October 2013 and February 2014, 140 participants were enrolled. Baseline HbA1c was 8.8% in each group. At 13-week follow-up, reduction in HbA1c was greater with metformin (-0.2%) than placebo (0.1%; mean difference, -0.3% [95% CI, -0.6% to 0.0%]; P = .02). However, this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2% in each group (mean difference, 0% [95% CI, -0.3% to 0.3%]; P = .92). At 26-week follow-up, total daily insulin per kg of body weight was reduced by at least 25% from baseline among 23% (16) of participants in the metformin group vs 1% (1) of participants in the placebo group (mean difference, 21% [95% CI, 11% to 32%]; P = .003), and 24% (17) of participants in the metformin group and 7% (5) of participants in the placebo group had a reduction in BMI z score of 10% or greater from baseline to 26 weeks (mean difference, 17% [95% CI, 5% to 29%]; P = .01). Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group (mean difference, 36% [95% CI, 19% to 51%]; P < .001). CONCLUSIONS AND RELEVANCE: Among overweight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months. Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, use of metformin resulted in an increased risk for gastrointestinal adverse events. These results do not support prescribing metformin to overweight adolescents with type 1 diabetes to improve glycemic control. TRIAL REGISTRATION: clinicaltrials.org Identifier: NCT01881828.