Metabolic Syndrome in Male Survivors of Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Impact of Total Body Irradiation, Low-Grade Inflammation, and Hypogonadism
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Metabolic Syndrome in Male Survivors of Pediatric Allogeneic Hematopoietic Stem Cell Transplantation : Impact of Total Body Irradiation, Low-Grade Inflammation, and Hypogonadism. / Muhic, Ena; Mathiesen, Sidsel; Nielsen, Malene Mejdahl; Suominen, Anu; Sørensen, Kaspar; Ifversen, Marianne; Nolsöe, Rúna Louise; Pedersen, Kasper Mønsted; Lähteenmäki, Päivi; Nordestgaard, Børge Grønne; Juul, Anders; Jahnukainen, Kirsi; Müller, Klaus.
I: Transplantation and Cellular Therapy, Bind 27, Nr. 9, 2021, s. 778.e1-778.e8.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Metabolic Syndrome in Male Survivors of Pediatric Allogeneic Hematopoietic Stem Cell Transplantation
T2 - Impact of Total Body Irradiation, Low-Grade Inflammation, and Hypogonadism
AU - Muhic, Ena
AU - Mathiesen, Sidsel
AU - Nielsen, Malene Mejdahl
AU - Suominen, Anu
AU - Sørensen, Kaspar
AU - Ifversen, Marianne
AU - Nolsöe, Rúna Louise
AU - Pedersen, Kasper Mønsted
AU - Lähteenmäki, Päivi
AU - Nordestgaard, Børge Grønne
AU - Juul, Anders
AU - Jahnukainen, Kirsi
AU - Müller, Klaus
N1 - Publisher Copyright: © 2021 The American Society for Transplantation and Cellular Therapy
PY - 2021
Y1 - 2021
N2 - Metabolic syndrome (MetS) is a growing concern in survivors of pediatric hematopoietic stem cell transplantation (HSCT), but little is known about the underlying mechanisms. This study aimed to determine the prevalence and clinical presentation of MetS in male long-term survivors of pediatric HSCT and to investigate predisposing factors, including low-grade inflammation, altered fat distribution, and low testosterone levels. We included 98 survivors age 19 to 47 years at a median follow-up of 18 years (range, 8 to 35 years) after pediatric HSCT. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence and clinical manifestations of MetS were compared between our cohort and a control group of males from the background population (n = 4767). Fat distribution was assessed by android/gynoid ratio from a whole-body dual-energy X-ray absorptiometry scan. Systemic inflammation was evaluated by IL-6 and high-sensitivity C-reactive protein (hsCRP). Serum testosterone levels were measured in morning samples. The prevalence of MetS was 30%, corresponding to the prevalence in the 50- to 80-year-old males from the background population. In individuals with MetS, hyperglycemia was more frequent in the HSCT survivors compared with age-matched controls with MetS (76% versus 20%; P < .001), whereas hypertension was more dominant in the control group with MetS (69% versus 93%; P = .01). In addition, normal or low body mass index was more commonly observed among HSCT survivors with MetS compared with age-matched controls with MetS (41% versus 11%; P = .002). MetS was more often associated with total body irradiation (TBI) compared with chemotherapy regimens (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.2 to 24.4; P = .02), lower testosterone levels (OR, 5.4; 95% CI, 1.3 to 23.6; P = .02), higher IL-6 levels (OR, 1.8; 95% CI, 1.2 to 2.8; P = .004), and higher hsCRP levels (OR, 1.8; 95% CI, 1.3 to 2.6; P < .001) (estimates per 2-fold increase). In addition, an increased android/gynoid (AG) fat ratio was strongly associated with MetS (OR, 2.1; 95% CI, 1.5 to 2.9; P < .001), even though only 7% of patients met the criteria for increased abdominal circumference. Our results indicate an increased risk of MetS in early adulthood after pediatric HSCT. The clinical manifestations differed from those seen in age-matched controls with MetS, indicating different pathophysiology driven by hyperglycemia, altered fat distribution (despite no clinical abdominal obesity), and low-grade inflammation. Risk factors included TBI-based conditioning and low testosterone levels. These results underline the importance of continuous clinical assessment of the cardiometabolic risk profile and stress the presence of important dissimilarities in the pathophysiology of MetS in HSCT survivors compared with the background population.
AB - Metabolic syndrome (MetS) is a growing concern in survivors of pediatric hematopoietic stem cell transplantation (HSCT), but little is known about the underlying mechanisms. This study aimed to determine the prevalence and clinical presentation of MetS in male long-term survivors of pediatric HSCT and to investigate predisposing factors, including low-grade inflammation, altered fat distribution, and low testosterone levels. We included 98 survivors age 19 to 47 years at a median follow-up of 18 years (range, 8 to 35 years) after pediatric HSCT. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence and clinical manifestations of MetS were compared between our cohort and a control group of males from the background population (n = 4767). Fat distribution was assessed by android/gynoid ratio from a whole-body dual-energy X-ray absorptiometry scan. Systemic inflammation was evaluated by IL-6 and high-sensitivity C-reactive protein (hsCRP). Serum testosterone levels were measured in morning samples. The prevalence of MetS was 30%, corresponding to the prevalence in the 50- to 80-year-old males from the background population. In individuals with MetS, hyperglycemia was more frequent in the HSCT survivors compared with age-matched controls with MetS (76% versus 20%; P < .001), whereas hypertension was more dominant in the control group with MetS (69% versus 93%; P = .01). In addition, normal or low body mass index was more commonly observed among HSCT survivors with MetS compared with age-matched controls with MetS (41% versus 11%; P = .002). MetS was more often associated with total body irradiation (TBI) compared with chemotherapy regimens (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.2 to 24.4; P = .02), lower testosterone levels (OR, 5.4; 95% CI, 1.3 to 23.6; P = .02), higher IL-6 levels (OR, 1.8; 95% CI, 1.2 to 2.8; P = .004), and higher hsCRP levels (OR, 1.8; 95% CI, 1.3 to 2.6; P < .001) (estimates per 2-fold increase). In addition, an increased android/gynoid (AG) fat ratio was strongly associated with MetS (OR, 2.1; 95% CI, 1.5 to 2.9; P < .001), even though only 7% of patients met the criteria for increased abdominal circumference. Our results indicate an increased risk of MetS in early adulthood after pediatric HSCT. The clinical manifestations differed from those seen in age-matched controls with MetS, indicating different pathophysiology driven by hyperglycemia, altered fat distribution (despite no clinical abdominal obesity), and low-grade inflammation. Risk factors included TBI-based conditioning and low testosterone levels. These results underline the importance of continuous clinical assessment of the cardiometabolic risk profile and stress the presence of important dissimilarities in the pathophysiology of MetS in HSCT survivors compared with the background population.
KW - Hematopoietic stem cell transplantation
KW - Late effects
KW - Long-term survivors
KW - Metabolic syndrome
KW - Pediatrics
U2 - 10.1016/j.jtct.2021.05.025
DO - 10.1016/j.jtct.2021.05.025
M3 - Journal article
C2 - 34091072
AN - SCOPUS:85110528766
VL - 27
SP - 778.e1-778.e8
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
SN - 2666-6375
IS - 9
ER -
ID: 275774445