We thank Dr. Steinherz for highlighting data on the long-term follow-up of patients after anthracycline treatment. Nevertheless, there remains a concerning lack of prognostic information from adequately powered controlled studies assessing cardiac function in patients more than 10 years after anthracycline therapy. For example, in one of Steinherz and colleagues' reports [1], no control group was used for comparison; because of the abstract format of the report, few specific clinical details are available on the patients studied. In our review we attempted to concentrate on follow-up studies of anthracycline recipients that were as detailed as possible in order to allow a more considered interpretation of the results. The confounding factors that we mentioned in our conclusion, such as heterogeneity of the study patients and preexisting heart disease, are difficult to dissect in abstracts. Thus, we await the publication of full-length reports of such studies as that of Steinherz and colleagues on the extended follow-up of patients more than a decade after treatment with anthracyclines. The 4 of 20 patients with new-onset ventricular dysfunction whom we mentioned in our review were indeed described by Dr. Steinherz's group in 1991. These researchers' 1993 report [2] discusses a pilot study that assessed 18 children who received continuous infusion of danorubicin but that lacked concurrent controls. As stated in our review, it is therefore clear that the overall benefit derived from continuous infusion of anthracycline in children in terms of antineoplastic effect versus cardiotoxicity still awaits rigorous proof.

Because of space limitations, we did not discuss the abnormalities of myocardial carnitine seen with anthracycline treatment or the potential cardioprotective effects of L-carnitine. However, anthracycline treatment can lead to altered fatty-acid transport and abnormal myocardial energy production [3]. L-carnitine is involved in the transport of long-chain fatty acids to mitochondrial sites of myocardial energy production. In addition, a recent report has indicated that tissue levels of free carnitine and high-energy phosphate were reduced in hearts treated with adriamycin for 3 to 6 weeks [4]. Consistent with these findings, in vitro data suggest that carnitine derivatives significantly reduce anthracycline-induced metabolic impairment in myocardial tissue [5]. These findings, together with the presentation cited by Dr. Klein, provide a possible pathophysiologic rationale for further investigation of using L-carnitine to provide cardioprotection against anthracycline-induced cardiomyopathy.