Diabetes, Hypertension and Cardiovascular Events in Survivors of Hematopoietic Cell Transplantation (HCT): A Report from the Bone Marrow Transplant Survivor Study.
Authors: Baker K. Scott , Ness Kirsten , Steinberger Julia , Carter Andrea , Francisco Liton , Burns Linda , Sklar Charles , Forman Stephen , Weisdorf Daniel , Gurney James , Bhatia Smita 
Published: April 2020

Abstract
Early evidence indicates that survivors after HCT may be at increased risk for metabolic syndrome (MS), characterized by obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension (HTN). Individuals with MS are at a higher risk for development of cardiovascular disease. The purpose of this analysis was to ascertain the prevalence of self-reported medical late effects including diabetes, HTN, myocardial infarction (MI), stroke, and obesity (body mass index [BMI] of 30 kg/m2 or greater) in a cohort of patients treated with HCT; to compare these outcomes in HCT survivors to a sibling comparison group, and to identify risk factors for these conditions after HCT.
Methods: Participants had undergone HCT at either City of Hope or the University of Minnesota for cancer or hematologic disorders between 1974 and 1998 and survived two or more years after HCT. A random sample of siblings of study participants was recruited for comparison. Participants (n=1276 cases, n=383 siblings) completed a 238-item health survey assessing medical conditions and medication use.
Results: Median age at HCT was 32.9 yrs (0.2–68.5) and median length of follow-up was 7.1 yrs (2–27) since HCT. The median age at completion of survey was 42.1 yrs (4.1–72.9) for HCT survivors and 41.4 yrs (1.6–78.7) for siblings. HCT survivors were more likely to be male (55.0% vs. 38.9%, p &lt; 0.001) than were siblings. Leukemia was the most common diagnosis (32.6%), 58.8% of survivors received an allogeneic HCT, and 75.9% received total body irradiation (TBI) as part of their conditioning regimen. CGVHD had been diagnosed in 48.5% of allogeneic HCT survivors, and those still receiving calcineurin inhibitors or steroids were excluded from the analysis. Survivors were more likely than siblings to report diabetes (8.0% vs. 3.1%) and HTN (22.8% vs. 15.7%). The prevalence of obesity was 19.8% among siblings and 15.9% among HCT survivors. The proportion of participants reporting arterial disease, a history of MI or stroke was less than 2% in each group. Adjusting for age at survey, age at HCT and sex, HCT survivors were 3.0 times (95% CI: 1.6–5.6) more likely to report diabetes and 1.6 times (95% CI: 1.1–2.1) more likely to report HTN than siblings. HCT survivors who received allo-HCT were 4.1 times (95% CI 2.1–7.9) more likely to report diabetes, 2.3 times (95% CI: 1.6–3.2) more likely to report HTN, and 7.9 times (95% CI 1.1–56.5) more likely to report stroke than siblings, whereas auto-HCT survivors were not more likely than siblings to report any of the conditions in this analysis. HCT survivors who received TBI were only more likely to report diabetes (OR=3.1, 95% CI: 1.5–6.3) than those not exposed to TBI. Allogeneic HCT increased the risk of diabetes (OR=2.1, 95% CI: 1.2–3.3) and HTN (OR= 2.4, 95% CI: 1.7–3.4) compared to autologous HCT. HCT survivors were 30% (95% CI: 10–40%) less likely than siblings to be obese.
Conclusions: HCT survivors, particularly those receiving allo-HCT and TBI, have a higher age-adjusted risk of diabetes and HTN that is independent of obesity, and that may predispose them to early cardiovascular events. Appropriate monitoring for the components of MS and interventions to decrease cardiovascular risk should be undertaken in this population.