Prevalence of Metabolic Syndrome among Childhood Leukemia Survivors Treated with and without Hematopoietic Cell Transplantation
Authors: Chow Eric J , Sanders Jean E , Roth Christian , Hoffmeister Paul A , Friedman Debra L 
Published: April 2020

Abstract
Survivors of childhood acute lymphoblastic leukemia (ALL) may face an increased risk of developing the metabolic syndrome as adults, particularly those treated with hematopoietic cell transplantation (HCT). The metabolic syndrome is defined by obesity, hypertension, insulin resistance, and dyslipidemia (increased triglyceride levels and/or decreased high density lipoprotein [HDL] levels). In this prospective cross-sectional study, pediatric ALL survivors were recruited from July 2007 to August 2008 in order to compare the prevalence of metabolic syndrome traits among those treated with HCT versus conventional chemotherapy. Eligible survivors were 8–22 years of age, ≥1 year off-therapy or from date of HCT, in remission, and not currently receiving treatment for chronic graft versus host disease. Twenty-eight survivors treated with conventional chemotherapy and 15 treated with HCT were enrolled, at a mean age of 15 years (9 years from initial ALL diagnosis). Patients treated with conventional therapy were restricted by study design to include only those in first complete remission; in contrast, 53% of HCT survivors had at least one prior relapse. All HCT survivors received total body irradiation, while only 14% of non-HCT survivors received any form of cranial radiotherapy. The 2 groups were similar with respect to mean body mass index (BMI), proportions with central adiposity and blood pressures above pre-hypertension thresholds (≥120/80 or ≥90% for age, sex, and height), and serum glucose levels (see Table). The prevalence of overweight (BMI ≥25 or ≥85% for age and sex) was high for both groups (53% HCT; 29% non-HCT; p=0.19). HCT survivors had higher fasting insulin (p=0.03) and triglyceride levels (p&lt;0.01), and lower HDL levels (p&lt;0.01) versus conventionally treated survivors. Compared with conventionally treated survivors, HCT survivors also had lower adiponectin levels (p&lt;0.01) and borderline increased leptin levels (p=0.06), but levels of other inflammatory markers (interleukin-6, tumor necrosis factor-α, C-reactive protein, and selected cell adhesion molecules) were similar (data not shown). Overall, HCT survivors were significantly more likely to have multiple metabolic syndrome component traits (≥2 traits, OR = 4.6, 95% CI 1.1–19.4), and 27% of HCT survivors met actual syndrome criteria (≥3 of 5 component traits, adapted for pediatrics) compared with zero non-HCT survivors (p=0.01). Even after adjusting for growth hormone deficiency and treatment, HCT survivors remained at significantly increased risk of having ≥2 traits. In summary, although sample size was limited, this study suggests that components of the metabolic syndrome may manifest among HCT survivors at an early age, particularly insulin resistance and dyslipidemia.
TABLE
Characteristic Conventional HCT P-value n=28 n=15 †Median if data not normally distributed ‡Homeostasis model assessment of insulin resistance Male:female 10:18 10:5 0.06 History of chronic graft versus host disease, n (%) - 9 (60) - BMI z-score (mean ± SD) 0.62 ± 0.81 0.62 ± 1.26 1.00 Overweight (BMI ≥25/≥85% for age & sex), n (%) 8 (29) 8 (53) 0.19 Obese (BMI ≥30/≥95% for age & sex), n (%) 3 (11) 3 (20) 0.65 Waist &gt;90% for age & sex, n (%) 5 (20) 5 (33) 0.46 Blood pressure ≥90% for age, sex, height, n (%) 5 (20) 5 (33) 0.46 Glucose (mean ± SD), mg/dL 80 ± 7 80 ± 10 1.00 Insulin (median†, range), mU/L 5.7 (3.4, 26.9) 10.3 (1.0, 32.1) 0.03 HOMA-IR‡ (median†, range) 1.2 (0.6, 5.5) 2.1 (0.2, 6.7) 0.05 Triglyceride (median†, range), mg/dL 63 (16, 177) 149 (105, 327) &lt;0.01 HDL (mean ± SD), mg/dL 55 ± 9 44 ± 5 &lt;0.01 Adiponectin (median†, range), μg/mL 10.5 (6.0, 19.1) 7.8 (3.3, 33.5) &lt;0.01 Leptin (median†, range), ng/mL 8.7 (0.4, 83.2) 20.0 (4.4, 101.0) 0.09 Metabolic syndrome traits, n (%) ≥1 trait 14 (50) 14 (93) Overall&lt;0.01 ≥2 traits 6 (21) 8 (53) ≥3 traits 0 4 (27)