Increased Body Adiposity and Serum Leptin Concentrations in Very Long-Term Adult Male Survivors of Childhood Acute Lymphoblastic Leukemia

Abstract

Background: We evaluated the body composition and its association with hypogonadism in adult male long-term acute lymphoblastic leukemia (ALL) survivors. Methods: The cohort included 49 long-term male ALL survivors and 55 age-matched healthy controls. Fat and lean mass was assessed by dual-energy X-ray absorptiometry; blood biochemistry was obtained for adipokines and testicular endocrine markers. Results: As compared with controls, the ALL survivors (median age 29 years, range 25-38), assessed 10-28 years after ALL diagnosis, had higher percentages of body (p < 0.05) and trunk fat mass (p < 0.05), and a lower body lean mass (p < 0.001). Survivors had significantly higher levels of leptin and adiponectin and lower levels of insulin-like growth factor-binding protein 3. Body fat mass and percent fat mass correlated with serum leptin and sex hormone-binding globulin (SHBG) levels. Altogether, 15% of the ALL survivors and 9% of age-matched controls were obese (BMI ≥30). Obese survivors more often had hypogonadism, had received testicular irradiation, and needed testosterone replacement therapy compared to nonobese survivors. Conclusion: At young adulthood, long-term male ALL survivors have significantly increased body adiposity despite normal weight and BMI. Potential indicators of increased adiposity included high leptin and low SHBG levels. Serum testicular endocrine markers did not correlate with body adiposity.

Adipokines in young survivors of childhood acute lymphocytic leukemia revisited: beyond fat mass

“…Increased leptin and low adiponectin concentrations are possibly involved with an altered fat distribution and metabolic abnormalities among ALL survivors. 12,[16][17][18][19][20][21][22][23][24] To date, previous data comprising this ALL cohort have confirmed the relationship between CRT exposure and an altered fat distribution. 6) Male sex also plays a role in determining leptin concentrations, but no effect of CRT has been identified, 16,22) which is contrary to the well-established reports so far.…”

“…The absence of this relationship between fat mass, visfatin, and particularly leptin may also be explained by other factors that could have negatively influenced or confounded this relationship, such as the number of participants in this cohort (55 ALL survivors) and/or the BMI z-score and FMI interval, which were not sufficient to detect such a relationship. [16][17][18][19][20][21][22][23][24]29) In regards to CRT exposure, visfatin was the only affected www.e-apem.org adipokine; its levels decreased in the group exposed to CRT; the CRT dosage in this sample varied from 18-24 Gy. These results contrast with previous data that showed higher leptin and decreased adiponectin concentrations among ALL patients who underwent CRT.…”

“…Adipokines are secreted by the adipose tissue and are biological markers of MS; these substances exert their actions in a wide variety of pathophysiological processes, including obesity, inflammation, glucose metabolism, and endothelial dysfunction. [16][17][18][19][20][21][22][23][24]29) Based on previous studies performed using this same ALL cohort, both FMI and abdominal adipose tissue are influenced by CRT exposure, while female sex only affects FMI. 6) There is increasing interest in assessing adiposity and its relationship with adipokines among ALL patients, as adipokine dysfunction due to excessive obesity might influence weight gain and MS traits in this group of patients, even many years after therapy withdrawal.…”

“…To date, sex and CRT exposure are important determinants of this relationship and represent the most important factors to be analysed in ALL survivors to understand their role in metabolic disease. [2][3][4][5][6][7][8][9][10][11][12][16][17][18][19][20][21][22][23][24]29) Late endocrine effects of cancer and its treatment are considered to create a synergic interaction between the host's genetic characteristics, including sex, the disease itself, and treatment type, including chemotherapy and CRT exposure. 4,5) In this study, the relationship between body fat (represented by the BMI z-score and FMI) and adipokines could be established only between adiponectin (negatively related) and resistin (positively related), even though all adipokines are secreted by fat.…”

“…To date, previous data comprising this ALL cohort have confirmed the relationship between CRT exposure and an altered fat distribution [ 6 ]. Male sex also plays a role in determining leptin concentrations, but no effect of CRT has been identified [ 16 , 22 ], which is contrary to the well-established reports so far [ 17 - 20 , 23 , 24 ]. Thus, the aim of this study was to further evaluate this relationship between leptin and other adipokines (adiponectin, visfatin, and resistin) with body fat, sex, and CRT exposure in survivors of childhood ALL.…”