[Serial determination of anthracycline poisoning in children]

Dose-related cardiotoxicity limits enthracycline administration in patients with solid tumours or leukaemia. Many patients (70%) would probably benefit by receiving more than a total accumulative dose of 500 mg/m2. As a measure of myocardial function the left ventricular ejection fractions (EF) were determined from serial radionuclide angiograms in 62 children who had at least 3 studies (mean age 8.4 +/- 5.4 years). Seven patients who had clinical evidence of cardiac involvement and/or a marked decline in their EF underwent endmyocardial biopsy (9 x). The EF declined progressively from 63 +/- 7% prior to chemotherapy to 60 +/- 5%, 58 +/- 7% and 54 +/- 7% after low, medium and high-dose anthracycline, respectively in the non-biopsied children vs 58 +/- 4%, 54 +/- 7% and 48 +/- 4% in the biopsied patients. Anthracycline dosage was 129 +/- 42, 307 +/- 68 and 471 +/- 61 mg/m2 and 103 +/- 64, 303 +/- 73 and 536 +/- 93 mg/m2, respectively. The biopsies were obtained at a mean anthracycline dose of 408 mg/m2 when the EF was 46 +/- 5%, and graded according to the modified Billingham score; grade 1 (6 x), 1.5 (2 x) and 2.5 (1 x). A decline in the EF was seen in 89% of our patients throughout their chemotherapy course, with a statistical significance of p less than 0.02 in the biopsied patients after medium dose therapy which was not seen in the non-biopsied children until they were receiving anthracyclines.