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Subclinical Late Cardiomyopathy After Doxorubicin Therapy for Lymphoma in Adults

From the Service of Hematology and Department of Biostatistics Centre Hospitalier Lyon-Sud, Pierre Bénite, France.

Address reprint requests to B. Coiffier, MD, Service d'Hématologie, Centre Hospitalier Lyon-Sud, 69495 Pierre-Bénite Cedex; e-mail: bertrand.coiffier{at}chu-lyon.fr

PURPOSE: To assess the cardiac status of the long-term survivors and to estimate the incidence and the features of subclinical cardiotoxicity induced after conventional treatment with doxorubicin for non-Hodgkin's lymphoma or Hodgkin's lymphoma.

PATIENTS AND METHODS: We analyzed a group of patients who previously received doxorubicin-based chemotherapy for lymphoma. Echocardiograms were performed at least 5 years after therapy with anthracyclines. Clinical cardiomyopathy was defined by the presence of clinical signs of congestive heart failure (CHF). Subclinical cardiomyopathy was defined by decrease of left ventricular fractional shortening (FS) without clinical signs of CHF. Cumulative dose of doxorubicin, male sex, older age, relapse, radiotherapy (mediastinal or total-body irradiation), autologous stem-cell transplantation, high-dose cyclophosphamide, and cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, familial history of cardiac disease, being overweight, and smoking history) were evaluated as potential risk factors for the development of cardiac dysfunction.

RESULTS: Of 141 assessable patients (median age, 54 years; median cumulative dose of doxorubicin, 300 mg/m²), only one developed CHF. Criteria of subclinical cardiomyopathy were found in 39 patients. In multivariate analysis, factors that contributed to decreased FS were male sex (P < .01), older age (P < .01), higher cumulative dose of doxorubicin or association with another anthracycline (P = .04), radiotherapy (P = .04), and being overweight (P = .04).

CONCLUSION: Cardiac abnormalities can occur in patients treated with doxorubicin for lymphoma in the absence of CHF, even in patients who received moderate anthracycline doses. Male sex, older age, higher dose of doxorubicin, radiotherapy, and being overweight were risk factors for the development of cardiomyopathy.

Supported in part by an unrestricted grant from Chiron.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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