LAUSR

Recipients of allogeneic hematopoietic cell transplantation (HCT) are now surviving longer due to impressive reductions in early transplant-related mortality [1]. Delayed transplant-related mortality in long-term allogeneic HCT survivors now exceeds relapse-related mortality [2, 3]. For such patients surviving at 2 years, the probability of surviving 10 years beyond HCT is 85% [3]. However, survivors of allogeneic HCT have a threefold higher incidence of arterial events than after autologous HCT [4]. The traditional cardiovascular risk factors (hypertension, dyslipidemia, smoking, diabetes, and obesity) are associated with higher rates of arterial events in these patients and these occur relatively early, at a median age of 53 years [5]. Concurrent chemotherapy, radiation, chronic graft versus host disease, steroids, and other immunosuppressants are believed to modulate these risk factors, through endothelial damage, leading to premature atherosclerosis [4–7]. We created a prediction risk stratification model that incorporated specific risk factors associated with allogeneic HCT, using coronary stenosis as measured using cardiac computed tomography angiography (CCTA) to determine the presence of coronary artery disease (CAD). CCTA is a low-risk, non-invasive and highly sensitive diagnostic tool to assess coronary atherosclerotic burden [8, 9]. We selected patients from a cohort of long-term survivors of allogeneic HCT initially recruited between the years 1993 and 2012 at the National Heart, Lung and Blood Institute. All patients included in the survivorship cohort had to have survived ≥3 years post-transplant [median follow-up 8 years (IQR 4–13)]. All patients received total body irradiation (TBI) and a 3–4 log ex vivo T-cell-depleted graft. Patients were recruited into our study if they presented for follow-up in our outpatient clinic between January 2015 and September 2017 and had no CAD history and could undergo CCTA [10]. Our end point was the presence of CAD as demonstrated by the CCTA-based segment involvement score that quantifies coronary artery plaque burden [11]. Each of the 16 coronary segments was assigned a score of 1 if any stenosis (plaque) was identified, regardless of severity. A total score was generated by adding the total number of coronary segments with plaque [11]. Patients were considered to have CAD if their score was ≥1. Our predictive model included: smoking, arterial hypertension, obesity (BMI > 30), diabetes, CAD family history, dyslipidemia, age, ethnicity/race, sex, and these allogeneic HCT risk factors: chronic graft versus host disease; ≥3 years steroid or other immunosuppressive treatment; immunosuppression at the time of CCTA (immunomodulators and/or systemic steroids); TSH/ hypothyroidism; chronic kidney disease (CKD) stage/glomerular filtration rate (GFR); high sensitivity C-reactive protein (hs-CRP); and any proteinuria. We used stepwise logistic regression analysis to examine the association of these risk factors with the presence of plaque on CCTA. Our model incorporated traditional cardiovascular risk factors as well as HCT-specific clinical variables that best fit our data. The area under the ROC curve (C-statistic) was used to assess the strength of the model. * Kimberley Doucette [email protected]