Leukemia Patients Treated With Anthracyclines Have Increased Risk of Heart Failure in Study

Patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who were treated with anthracyclines had a heightened risk of heart failure in a new study, which found the risk was greatest within the first year of exposure to chemotherapy.

At the same time, the researchers from Penn Medicine were able to develop and confirm a risk score model that can be used to gauge which patients are at increased risk for heart failure from chemotherapy.

The study was published in JACC: CardioOncology, a publication of the American College of Cardiology (ACC).

As more patients with cancer survive, the risk of cardiac complications due to the effects of therapies has become a concern to oncologists and cardiologists alike. The ACC has taken a particular interest in promoting research and collaboration in this area.

"While we are more effective at treating cancer, the improved survival rates have helped to unmask the cardiotoxic impact of some of the most common cancer therapies," study author Marielle Scherrer-Crosbie, MD, PhD, a professor of Cardiovascular Medicine in the Perelman School of Medicine at the University of Pennsylvania, said in a statement. "Our hope, in creating this risk score system, is to help clinicians identify patients with the highest risk for potential cardiac damage, so they can more closely monitor the patients via a multidisciplinary approach."

Incidence of leukemia, including acute leukemia, has increased in the United States over the past decade as the baby boomer generation ages. At the same time, therapeutic advances have caused mortality rates to decline by 1% each year from 2006 to 2015.

Anthracyclines remain a standard therapy for acute leukemia, and these treatments typically involve high doses delivered over a short period, resulting in toxic effects.

In this new study, Penn Medicine researchers examined data from 450 patients with ALL, which occurs when the bone marrow makes too many lymphocytes, or AML, which occurs when bone marrow makes abnormal myeloblasts. Of this group, 40 patients (8.9%) developed symptomatic heart failure; on average, they developed the condition 10 months after treatment. Patients with AML were more likely to develop heart failure.

The researchers developed a risk score, on a scale of 0 to 21, which examined 6 variables of myocardial strain measurable by echocardiography. Points were assigned based on each variable:

• a baseline global longitudinal strain (GLS) of greater than 15% (6 points)
• baseline left ventricle ejection fraction of less than 50%
• pre-existing heart disease,
• AML (4 points each);
• cumulative anthracycline dose of greater than or equal to 250 mg/m (2 points)
• being older than 60 years of age (1 point).

Patients were placed in 3 groups based on risk score for heart failure: low (0 to 6), moderate (7 to 13) and high (14 to 21). Most patients were deemed low risk (n = 318), with 112 classified as moderate risk and 20 classified as high risk. Researchers confirmed that 65% of the high-risk patients developed heart failure, compared with 1% of the low-risk group.

According to the abstract, the estimated 1-year cumulative incidence of HF for low-, moderate-, and high-risk groups was 1.0%, 13.6%, and 35.0%, respectively (P < .001). The heart failure risk score was also predictive of all-cause mortality (P < .001). However, after adjusting for age and leukemia type, only GLS was significantly associated with all-cause mortality (hazard ratio: 1.73; 95% CI: 1.30-2.31; P < .001).

"While this is a significant step toward identifying patient risk for heart failure, additional studies are needed to determine the effectiveness of such a risk score in clinical practice," said lead author Yu Kang, MD, PhD, a post-doctoral research fellow at Penn, in the statement.

Reference

Kang Y, Assuncao BL, Denduluri S, et al. Symptomatic heart failure in acute leukemia patients treated with anthracyclines. JACC: CardioOncology. 2019:1(2):208. doi:10.1016/j.jaccao.2019.10.008.