Cardiac Complications Following Allogeneic Bone Marrow Transplantation: Evaluation of Risk Factors, Outcomes and Enhanced Screening for At Risk Populations.
Authors: Henry Michael , Guo Rong , Parthasarathy Mala , Lopez John , Stiff Patrick 
Published: October 2019

Abstract
Abstract 3070
Life-threatening cardiac events following allogeneic bone marrow transplants (BMT) are not uncommon at 5–12.5% of patients. While BMT programs perform screening EKGs and ejection fraction measurements, solid organ transplant centers follow a risk stratification screening algorithm to assess for coronary artery disease (CAD) which includes stress tests and as indicated, angiography in those with 2 or more risk factors. It is currently unknown whether this algorithm should be applied in the BMT setting.

Methods:
We performed a retrospective review of 296 patients who underwent allogeneic BMT at Loyola University Medical Center 2007–2011, to assess cardiac events using the solid organ transplant advanced screening criteria: age over 60 or over 40 with peripheral vascular disease or diabetes and then divided patients into low risk (one CV risk factor) and high risk groups (greater than one CV risk factor). Risk factors included age, hypertension, diabetes, smoking, family history of CAD, and obesity according to the Framingham risk assessment score for CAD. Cardiac events during the first year post-transplant were recorded including CHF, myocardial infarction (MI), and symptomatic arrhythmias. One hundred day and 1-year Kaplan-Meier survival for high and low risk patients were determined and curves compared by log-rank tests. A multivariate analysis of the various prognostic factors was performed using the Cox regression model.

Results:
Of the 296 total allografts, 116 patients (39%) fit the solid organ transplant criteria for advanced screening; 62% were male (n = 72) and the mean age was 60.6 (range 40–72). Graft source was evenly distributed between siblings (42%), unrelated (39%) and cord blood (28%). Acute myeloid leukemia was the most common indication for BMT at 40%, followed by MDS (21%), non-Hodgkin lymphoma (16%), and CLL (10%). Of the 116, 21 were considered low risk (1 risk factor), while 95 were high risk (2+ risk factors). Low risk and high risk groups did not differ in disease type (p = 0.43), graft source (p = 0.81), or graft type (p = 0.54). Surprisingly, both high and low risk patients had a similar incidence of cardiac events of 36% and 48%, respectively. This correlated to comparable 100-day and 1 year survival rates. To determine the importance of cardiac complications on outcome and whether there were other risk factors for complications we analyzed those with a complication. Forty-four cardiac events occurred in the first year after transplant in 38 (33%) patients. Cardiac events included arrhythmias (n = 33), new onset CHF (n = 6), and MI (n = 5). Median time to event was 16 days post-transplant. Symptomatic arrhythmias included atrial fibrillation (n = 27, 82%), supraventricular tachycardia (n = 5, 15%) and sustained ventricular tachycardia (n =1, 3%). Median age for patients with cardiac events was 62.7 years, compared to 59.6 for patients who experienced no cardiac events (hazard ratio estimate: 1.076; p = 0.02). As compared to patients with no post-transplant cardiac events, both the 100 day and 1 year survival rates of patients with cardiac events were lower with one year survival of 21% vs. 63% (p < 0.0001). Evaluating risk factors, 3 were significant: donor source with MUD donors the highest hazard (p = 0.04); age, with cardiac events occurring at a rate twice as high in patients greater than age 60 (n = 27, 36.5% vs. n = 6, 19.4%), and with all five cases of myocardial infarction and 5/6 new CHF diagnoses occurring in patients aged 60 or greater; and patients with a history of atrial fibrillation demonstrated a higher probability of developing a cardiac event post-transplant (p = 0.02).

Conclusions:
In this analysis, we saw a much higher incidence of post-BMT cardiac events (33%) than previously reported, although we focused only on at risk patients using the solid organ screening algorithm (pts > 40 with significant risk factors or all pts > 60). As mortality rates at 100 day and 1 year are higher for patients who suffer a post-BMT cardiac event, and only graft source, age and prior atrial fibrillation marked patients at a very high risk, this data indicates that it is appropriate to investigate prospectively the solid organ transplant algorithm in all allogeneic BMT patients > age 40, with low cardiac risk or any patient > 60 with stress tests and as indicated, cardiac catheterization. Whether this will decrease events and thereby improve survival remains to be determined by prospective studies.

Disclosures:
No relevant conflicts of interest to declare.