ANTHRACYCLINE DOSE IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA - ISSUESOF EARLY SURVIVAL VERSUS LATE CARDIOTOXICITY

Purpose: Late abnormalities of left ventricular (LV) performance occur in most survivors of childhood acute lymphoblastic leukemia (ALL) tre ated with moderate anthracycline doses. We studied the prevalence of l ate cardiotoxicity in patients treated with lower anthracycline doses and related this to survival. Patients and Methods: Echocardiograms we re performed in 50 normal children and 120 relapse-free ALL survivors 6.2 +/- 2.0 years after the end of cumulative daunorubicin doses of 90 mg/m(2) (n = 40), 180 mg/m(2) (n = 40), or 270 mg/m(2) (n = 40) on UK ALL X pilot (1982 to 1984) or UKALL X (1985 to 1989) protocols, Age at treatment onset was 4.7 +/- 2.8 years. Cardiac abnormalities were rev iewed in light of the UKALL X 5-year disease-free survival rates of 57 % (95% confidence interval [CI], 51% to 63%), 61% to 62% (95% CI, 56% to 68%), and 71% (95% CI, 66% to 76%) for the groups that received 90, 180, and 270 mg/m(2) of daunorubicin, respectively. Results: ALL surv ivors had reduced LV fractional shortening (FS) compared with normal ( 32.3% +/- 4.4% v 35.9% +/- 4.2%, P <.005), which was accounted for by increased LV end-systolic stress (49.4 +/- 13.5 v 42.2 +/- 9.1 g/cm(2) , P <.001), whereas LV contractility independent of loading conditions was normal for the group as a whole. Of 27 patients (23%) with cardia c abnormalities, 25 (21%) had increased end-systolic stress, whereas o nly two (2%) had reduced contractility, The proportion with cardiac ab normality was similar in the three dose groups, Anthracycline dose, ag e at treatment, sex, follow-up duration, growth hormone, pubertal stat us, hemoglobin level, and total WBC count at presentation were not pre dictive of increased LV end-systolic stress. Conclusion: There was a r educed incidence and severity of cardiac abnormalities with the lower anthracycline dine dose protocols (90 to 270 mg/m(2)) studied compared with previous reports in which subjects had received moderate anthrac ycline doses (similar or equal to 300 to 550 mg/m(2)). Cumulative anth racycline dose within the range 90 to 270 mg/m(2) did not relate to ca rdiac abnormalities. This suggests that there may be no safe anthracyc line dose to avoid late cardiotoxicity, but reinforces the use of the protocol that affords best survival within the dose range studied. (C) 1997 by American Society of Clinical Oncology.