Persistent Cardiac Dysfunction Following Treatment of Childhood Malignancy Is Related to Cumulative Anthracycline Dose

Abstract 165 Poster Session III, Monday, 5/3 (poster 131)

Late cardiotoxicity following anthracycline therapy for malignancies in children is an important but poorly characterized clinical problem. The onset of late cardiotoxicity after therapy has been shown to be loosely related to the cumulative anthracycline dose (CumD), but there are no data published which characterize subsequent changes in cardiac function following the initial recognition of cardiotoxicity. We hypothesized that in patients with cardiac dysfunction, CumD would help stratify the risk that cardiac dysfunction would be persistent, and further hypothesized that a CumD of greater than 350 mg/m² would identify a patient subset at high risk of continued cardiac dysfunction. The study population included 344 pediatric patients who underwent echocardiography at Stanford between 1993 and 1998 for follow-up of anthracycline-containing chemotherapy. From this group, 30 pts were identified who had at least one echocardiogram with diminished cardiac function (fractional shortening ≤ 27%), and who had at least one subsequent echocardiogram. Median age at diagnosis was 8.0 yrs (1 week-18.6 yrs), anthracycline dose was 335 mg/m² (35-575 mg/m²), and follow-up was 2.8 yrs (0.6-18.6 yrs). Fifteen patients (50%) were male. Follow-up intervals were defined as 0-90 days post start of therapy, 91-180 days, 181 days-1yr, and yearly thereafter. Cardiac status was defined as normalized if the initial echocardiogram was the only abnormal echocardiogram, and persistently abnormal if echocardiograms during subsequent intervals had diminished function. The effect of CumD on cardiac status was evaluated using both contingency tables and logistic regression modeling. A total of 15 pts (50%) were classified as persistently abnormal. For CumD greater than 350 mg/m², 9/12 pts (75%) were persistently abnormal, as compared to 6/18 pts (33%) with CumD ≤ 350 mg/m² (p=0.02). By logistic regression, CumD was predictive of an increased likelihood of cardiac function remaining abnormal, with an odds ratio of 2.4 for each increment of 100 mg/m². CONCLUSION: In pts with one episode of cardiac dysfunction, the likelihood of persistently abnormal echocardiograms is related to the cumulative dose of anthracycline. Some patients may return to normal cardiac function. For patients with cumulative doses greater than 350 mg/m2, the risk of persistent cardiac dysfunction is quite high and warrants close follow-up.