NEW YORK (Reuters Health) - Anthracycline-containing chemotherapy (ACCT) is associated with valvular dysfunction (VD) and degeneration in lymphoma survivors who have undergone stem cell transplant, according to new research.
Cardiac radiotherapy increases VD risk, and anthracyclines are known to have dose-dependent cardiotoxic effects, Dr. Klaus Murbraech, of Oslo University Hospital, and colleagues write in their report online February 17 in Journal of the American College of Cardiology - Cardiovascular Imaging. However, they add, prevalence and risk factors for VD in adult lymphoma survivors who undergo autologous hematopoietic stem cell transplantation (auto-HCT) are unclear.
To investigate, and learn whether patients who received anthracycline therapy but not radiation were at increased risk of VD, the researchers compared 274 lymphoma survivors who had received auto-HCT between 1987 and 2008 in Norway and controls drawn from a clinical echocardiographic database. None of the controls had been diagnosed with cardiovascular disease, hypertension, or diabetes.
The mean follow-up time since diagnosis was 13 years, and 62% of study participants were men. The mean cumulative anthracycline dosage was 316 mg/m2, and just over one-third had received radiation involving the heart.
Sixty-one lymphoma survivors (22.3%) had a total of 82 dysfunctional valves, and seven survivors had severe VD. Among patients who received ACCT, 16.9% had VD, triple the risk for controls (odds ratio 3.3, p<0 .001="" and="" aortic="" but="" comparable="" controls="" higher.="" mitral="" of="" p="" regurgitation="" risk="" significantly="" that="" their="" to="" tricuspid="" was="">
Risk factors independently associated with VD among the lymphoma survivors included female gender (OR 2.0), age 50 or older at diagnosis (OR 3.4), receiving at least three lines of chemotherapy before HCT (OR 2.9), and having received a cardiac radiotherapy dose above 30 Gy (OR 5.3).
Among the patients treated with ACCT who did not receive radiation, being 50 or older (OR 5.7) and receiving at least three lines of chemotherapy before HCT (OR 4.4) were both significantly associated with VD. A cardiac radiotherapy dose of 30 Gy or below did not further increase VD risk in patients who received ACCT.
"The majority of VD observed was moderate, and longer observation time is necessary for further clarification of the clinical significance of (these) findings," the researchers conclude.
"Although this is a cross-sectional study with no report of prior echoes, the data supporting the hypothesis that anthracycline-containing chemotherapy can cause direct valve injury is compelling," Dr. Michael H. Crawford, of the University of California at San Francisco, writes in an editorial accompanying the study.
"Further basic and clinical research need to be done to elucidate this intriguing concept. At this time it seems prudent to consider valve disease in long-term lymphoma survivors whether they received radiation or chemotherapy or especially both at high doses as a young person (<25 adds.="" age="" agents="" also="" cause="" chemotherapeutic="" crawford="" dr.="" effects="" erhaps="" have="" heart="" injury="" known="" long-term="" myocardial="" newer="" of="" on="" other="" p="" these="" to="" valves.="" will="" years="">0>
Dr. Murbraech did not respond to an interview request by press time.
The South-Eastern Norway Regional Health Authority and Extrastiftelsen supported this study. One coauthor reported disclosures.
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