Lymphoma Survivors at Greater Risk for Heart Failure After Autologous Transplantation

Survivors of lymphoma who underwent autologous hematopoietic stem-cell transplantation (HSCT) may be at greater long-term risk for heart failure and left ventricular systolic dysfunction than previously thought, according to the results of a new study conducted by researchers led by Klaus Murbraech, MD, of the department of cardiology at Oslo University Hospital.

In the study, the researchers not only found an increased prevalence for these cardiac risks but also identified two independently associated risk factors: cardiac radiation therapy of 30 Gy or greater and cumulative doxorubicin dose of 300 mg/m² or greater.

“Our findings may help identify lymphoma survivors at increased risk of left ventricular systolic dysfunction after autologous HSCT and can serve as a basis for developing intensified surveillance strategies for these patients,” wrote Murbraech and colleagues in the Journal of Clinical Oncology.

Their national cross-sectional study looked at all patients who survived lymphoma and were treated with autologous HSCT in Norway from 1987 to 2008. Occurrence of asymptomatic left ventricular systolic dysfunction-defined as a left ventricular ejection fraction of less than 50%-and heart failure were compared among these patients and a group of healthy controls.

The researchers looked at 274 lymphoma survivors with a mean time from diagnosis of 13 years. This group of survivors had undergone a mean cumulative dose of doxorubicin of 316 mg/m² and 35% received additional radiation therapy that involved the heart.

Left ventricular systolic dysfunction was found in 15.7% of the survivors; 10.6% of the survivors had overt heart failure and 5.1% had asymptomatic left ventricular systolic dysfunction. About 8% of survivors had New York Heart Association class II heart failure. 

“The lymphoma survivors with heart failure were predominantly mildly affected but had a significantly reduced exercise capacity compared with those with asymptomatic left ventricular systolic dysfunction,” the researchers wrote. “Severe symptomatic heart failure was rare.”

When compared with the group of healthy controls, the researchers found that the lymphoma survivors were at six times the risk for left ventricular systolic dysfunction (OR = 6.6; 95% CI, 2.5–17.6; P < .001). Both doxorubicin dose of 300 mg/m² or more (OR = 3.3; 95% CI, 1.2–8.9; P = .02) and cardiac radiation therapy dose of greater than 30 Gy (OR = 4.3; 95% CI, 1.7–11.4; P = .003) were found to be independently associated with this increased cardiac risk.

“To overcome a possible bias in the selection criteria, comparisons with controls were performed after excluding lymphoma survivors already diagnosed with cardiovascular disease, hypertension, or diabetes at survey. Furthermore, by applying the same exclusion criteria in the lymphoma survivors as in the matched control group, we present a more reliable result,” the researchers wrote. “However, this adjustment may actually have led to an underestimation of the reported risk of left ventricular systolic dysfunction in the lymphoma survivors.”