Metabolic Syndrome after Hematopoietic Cell Transplantation: At the Intersection of Treatment Toxicity and Immune Dysfunction

Turcotte, Lucie M.; Yingst, Ashley; Verneris, Michael R.

doi:10.1016/j.bbmt.2016.03.016

Cited by 28 publications

(19 citation statements)

References 79 publications

(88 reference statements)

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“…Immune dysfunction and alterations in adipose tissue hemostasis and development of proinflammatory state could contribute to the MetS and its components . It could also be due to the limited physical activity and lifestyle of HSCT survivors, especially in the first 2 years post‐transplant . Our findings are important as early intervention and recommendations for healthy lifestyle may prevent premature cardiovascular morbidity.…”

Section: Discussionmentioning

confidence: 89%

The metabolic syndrome and its components in pediatric survivors of allogeneic hematopoietic stem cell transplantation

Bielorai

Weintraub

Hutt

et al. 2017

Clinical Transplantation

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Metabolic syndrome (MetS) is a known complication after hematopoietic stem cell transplantations (HSCT) that contributes to long-term morbidity. We assessed the prevalence of components of the MetS in pediatric survivors of allogeneic HSCT and identified associated risk factors. Thirty-eight patients, median age at HSCT, 8.5 years, were evaluated at a median of 3.9 years post-HSCT. Overweight or obesity was seen in 23.7% of the patients, 15.8% had hypertension, 15.8% had hypertriglyceridemia, and 13% had low high-density lipoprotein cholesterol levels according to age and gender. Four (10.5%) met the criteria of MetS; all were transplanted for malignant disease. Twelve patients (31.6%) had at least one component of the MetS. The 5-year probability of developing components of the MetS revealed that patients with BMI-Z score ≥0 at HSCT were significantly at higher risk than those with lower BMI-Z. Patients who developed components of the MetS had higher levels of insulin, homeostasis model assessment, uric acid, leptin, and lower adiponectin levels. Multivariable regression analysis revealed that BMI-Z-score >1.036 at time of evaluation was associated with 4.3-fold increased risk (P=.050) and adiponectin levels ≤6 μg/mL were associated with 6.7-fold increased risk of develop components of the MetS (P=.007). Overweight and obesity and adiponectin levels may be useful as markers in HSCT survivors.

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Section: Discussionmentioning

confidence: 89%

The metabolic syndrome and its components in pediatric survivors of allogeneic hematopoietic stem cell transplantation

Bielorai

Weintraub

Hutt

et al. 2017

Clinical Transplantation

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“…23 Dysfunctional adipose tissue, rather than obesity per se , may play an important role in the pathogenesis of metabolic syndrome in TBI-exposed HCT survivors. 59 …”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Risk Factors in Survivors of Childhood Hematopoietic Cell Transplantation Treated with Total Body Irradiation: A Longitudinal Analysis

Friedman

Hilden

Moskowitz

et al. 2017

Biology of Blood and Marrow Transplantation

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Hematopoietic cell transplantation (HCT) survivors treated with total body irradiation (TBI) are known to be at increased risk for the development of cardiovascular risk factors (CVRF). We sought to characterize the incidence of CVRF in a TBI-exposed survivor cohort and describe prognostic indicators of their development. Retrospective analysis of CVRF in 1-year survivors of leukemia or lymphoma treated with TBI at Memorial Sloan Kettering from April 1987–May 2011. Eligible participants were≤ 21 years of age at TBI and were not on glucocorticoids at the time of entry to Long-Term Follow-Up. Survivors were assessed for obesity (body mass index [BMI]≥ 95th% for ages≤ 20; ≥30 kg/m2 for ages >20 years), elevated blood pressure, dyslipidemia (elevated triglycerides [TG], low high-density lipoprotein [HDL]), and glucose intolerance (fasting glucose ≥100 mg/dl); those with ≥3 risk factors were deemed to have a CVRF cluster, a surrogate for metabolic syndrome. Cox regression models were used to estimate hazard ratios (HRs) evaluating factors associated with each CVRF. In order to compare prevalence of CVRF in HCT survivors and the general population, survivors were compared to age-, sex-, and race-matched controls from the National Health and Nutrition Examination Survey (NHANES). 123 survivors were evaluated (62.6% male). Median age at TBI was 11.8 years (range 1.6–21.9); median followup was 8.0 years (1.01–24.6); median age at last followup 20.1 years (4.0–41.3). Five-year cumulative incidence of elevated blood pressure, elevated glucose, low HDL, hypertriglyceridemia, and obesity was 14.7%, 10.5%, 26.8%, 39.2%, and 16.0%, respectively, while 10-year cumulative incidence was 28.8%, 33.1%, 52.0%, 65.0%, and 18.6%, respectively. The cumulative incidence of CVRF cluster rose from 10.6% (5.6–17.5) at 5 years to 28.4% (18.8–38.7) at 10 years. In multivariate analysis, growth hormone (GH) deficiency (HR 8.6; 95% CI, 2.1–34.4, p=0.002), history of cranial radiation (HR 4.0; 95% CI, 1.7–9.6, p=0.002), and grade II-IV acute GVHD (HR 4.2; 95% CI, 1.5–12.2, p=0.008) were associated with risk of developing CVRF cluster. HCT survivors had an increased prevalence of hypertriglyceridemia and low HDL, but not glucose intolerance, elevated blood pressure, or CVRF cluster, when compared to a random sample of matched population controls. Given the young age of this HCT survivor cohort, these data highlight the importance of routine screening for CVRF starting in childhood among those exposed to TBI.

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“…Possible contributors to dyslipidemia include host factors, such as obesity and family history, in addition to TBI and transplant complications (i.e., GVHD, liver disease, and hormonal deficits) [57,58]. Immune system dysfunction, inflammatory mechanisms, and changes in microbiome composition were recently suggested to contribute to persistent metabolic derangements after HSCT; however, supporting evidence for this is lacking [59].…”

Section: Abnormal Body Composition Impaired Glucose Metabolism and mentioning

confidence: 99%

A systematic approach to the endocrine care of survivors of pediatric hematopoietic stem cell transplantation

Paetow

Bader

Chemaitilly

2020

Cancer Metastasis Rev

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Hematopoietic stem cell transplantation (HSCT) is used in children to treat a variety of malignant and nonmalignant hematologic conditions and certain inborn errors of metabolism. Survivors of HSCT are markedly affected by disease and treatment toxicity. Endocrine complications are among the most commonly reported chronic health conditions in this population. In this review, we summarize the most common endocrine late effects after pediatric HSCT. We also highlight the importance of systematic and longitudinal evaluations to achieve early diagnoses and treatment for these conditions and improve the long-term health outcomes for patients who received HSCT as children.

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Metabolic Syndrome after Hematopoietic Cell Transplantation: At the Intersection of Treatment Toxicity and Immune Dysfunction

Cited by 28 publications

References 79 publications

The metabolic syndrome and its components in pediatric survivors of allogeneic hematopoietic stem cell transplantation

The metabolic syndrome and its components in pediatric survivors of allogeneic hematopoietic stem cell transplantation

Cardiovascular Risk Factors in Survivors of Childhood Hematopoietic Cell Transplantation Treated with Total Body Irradiation: A Longitudinal Analysis

A systematic approach to the endocrine care of survivors of pediatric hematopoietic stem cell transplantation

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