{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:53:23Z","timestamp":1791147203869,"version":"4.1.0"},"reference-count":36,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,4,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Cross-sectional studies show that cardiac abnormalities are common in long-term survivors of doxorubicin-treated childhood malignancies. Longitudinal data, however, are rare. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> Serial echocardiograms (N = 499) were obtained from 115 doxorubicin-treated long-term survivors of childhood acute lymphoblastic leukemia (median age at diagnosis, 4.8 years; median follow-up after completion of doxorubicin, 11.8 years). Results were expressed as z scores to indicate the number of standard deviations (SDs) above (+) or below (\u2212) the normal predicted value. Median individual and cumulative doxorubicin doses were 30 mg\/m<jats:sup>2<\/jats:sup> per dose and 352 mg\/m<jats:sup>2<\/jats:sup>, respectively. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Left ventricular fractional shortening was significantly reduced after doxorubicin therapy, and the reduction was related to cumulative dose. z scores for fractional shortening transiently improved before falling to \u22122.76 more than 12 years after diagnosis. Reduced fractional shortening was related to impaired contractility and increasing afterload, consequences of a progressive reduction of ventricular mass, and wall thickness relative to body-surface area. Left ventricular contractility fell significantly over time and was depressed at last follow-up in patients receiving more than 300 mg\/m<jats:sup>2<\/jats:sup> of doxorubicin. Systolic and diastolic blood pressures were below normal more than 9 years after diagnosis. Even patients receiving lower cumulative doxorubicin doses experienced reduced mass and dimension. Fractional shortening and dimension at the end of therapy predicted these parameters 11.8 years later. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Cardiac abnormalities were persistent and progressive after doxorubicin therapy. Inadequate ventricular mass with chronic afterload excess was associated with progressive contractile deficit and possibly reduced cardiac output and restrictive cardiomyopathy. 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