Heart Damage in Patients With Lymphoma After Stem Cell Transplant

Veronica Hackethal, MD

July 16, 2015

Patients with lymphoma who have undergone autologous stem cell transplant (auto-HSCT) as adults may have six to seven times the risk for left ventricular systolic dysfunction (LVSD) compared with healthy individuals, according to a Norwegian study published online July 13 in the Journal of Clinical Oncology.

"LVSD is a common late effect in this group of cancer survivors, affecting approximately 1 out of 6 lymphoma survivors. Of course the threshold to see a cardiologist should therefore be low even with subtle symptoms," commented first author Klaus Murbraech, MD, from the Department of Cardiology at Oslo University Hospital in Norway.

"One could also argue for some kind of routine screening, especially for subgroups with higher cardiotoxic treatment burden," he added.

"In general I would like to urge for increased awareness, both in patients and clinicians, about increased risk for cardiovascular disease in lymphoma survivors, even many years after treatment exposure," Dr Murbraech emphasized.

Leading Cause of Death in Survivors

Cardiovascular disease accounts for the leading cause of noncancerous death among lymphoma survivors who have received stem cell transplants, the authors write. Past studies have suggested that such patients may have three times the risk for cardiovascular complications, according to background information in the article.

Heart failure can develop many years after therapy for lymphoma, with rates ranging from 2% to 9%. Anthracyclines, such as doxorubicin, and cardiac radiation therapy can contribute to increased cardiac risk, the authors note.

The study included lymphoma survivors who had received auto-HSCT as adults in Norway between 1987 and 2008. Participants completed self-reported questionnaires and had comprehensive medical exams, including echocardiography and exercise capacity testing. The researchers also obtained treatment details from medical records and the lymphoma registry at Oslo University Hospital.

The team defined LVSD as left ventricular ejection fraction less than 50% according to echocardiography. They defined heart failure using American College of Cardiology and American Heart Association criteria. The same investigator assessed images and was blinded to lymphoma treatment.

The analysis included 274 lymphoma survivors (69% of those eligible), of whom 62% were men (mean age, 56 ± 12 years) and 78% had non-Hodgkin's lymphoma. Patients had a mean follow-up time of 13 ± 6 years. They had received a mean doxorubicin dose of 316 ± 111 mg/m2. Thirty-five percent of lymphoma survivors had also undergone cardiac radiation therapy.

LVSD occurred in 15.7% of lymphoma survivors, of whom 5.1% had asymptomatic LVSD. Compared with age- and sex-matched controls, lymphoma survivors had "substantially" increased LVSD risk (odds ratio [OR], 6.6; 95% confidence interval [CI], 2.5 - 17.6; P < .001).

One of three lymphoma survivors with LVSD was asymptomatic and had peak oxygen consumption similar to of the general population.

Overt heart failure occurred in 29 patients (10.6%). Most patients with heart failure had mild symptoms, with 8.8% (n = 24) classified as New York Heart Association (NYHA) class II.

More severe heart failure (NYHA class III) occurred rarely (1.8%; n = 5), all in patients who had received cardiac radiation therapy plus anthracyclines. No participants had NYHA class IV heart failure.

Independent risk factors for LVSD included doxorubicin dose of 300 mg/m2 or greater (OR, 3.3; 95% CI, 1.2 - 8.9; P = .02) and cardiac radiation dose greater than 30 Gy (OR, 4.3; 95% CI, 1.7 - 11.4; P = .003, respectively). Patients treated with both anthracyclines and high-dose cardiac radiation therapy (>30 Gy) had the highest risk for LVSD.

"We identified doxorubicin dose over 300 mg/m2 and high-dose [cardiac] radiotherapy as independent risk factors for LVSD. Consequently, survivors with these treatment variables are at the highest risk for LVSD," Dr Murbraech pointed out.

Doxorubicin has dose-dependent cardiac toxicity, and heart failure rarely develops below a certain threshold dose, according to the authors. In accordance with other research, they suggested that a cumulative dose of 300 mg/m2 could be used as a threshold for estimating the risk for LVSD in lymphoma patients who have had auto-HCT.

One or more of the authors reports honoraria, advisory board membership, or consulting with one or more of the following: Actelion Pharmaceuticals, Pfizer, Bayer, and ResMed. One coauthor held a position at the MI Lab supported by GE.

J Clin Oncol. Published online July 13, 2015. Abstract

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