Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood

Introduction Late cardiotoxicity is a known complication of anthracycline therapy but the long-term effects of low cumulative doses are not well documented. We studied late cardiotoxicity in survivors of childhood acute lymphoblastic leukemia (ALL) treated with low anthracycline doses 10 to 20 years earlier. Methods Seventy-seven ALL survivors who received a cumulative anthracycline dose <250 mg/m(2) and were at least 10 years after treatment were evaluated for signs of clinical heart failure. Cardiac function was assessed by echocardiography including tissue Doppler measurements of the septal mitral annulus in 37 ALL survivors 10.6-18.3 years (median 13.3 years) after anthracycline treatment with cumulative doses of 180 (n=19) or 240 mg/m(2) (n=18). The control group consisted of 30 healthy volunteers matched for age, sex, BSA, and BMI. Results No clinical relevant cardiotoxicity was found. Left ventricular shortening fraction (SF) was significantly reduced in male ALL survivors. Three of the 19 male ALL survivors had an SF below 30%. Male ALL survivors showed a significantly lower early filling velocity to atrial contraction velocity ratio but myocardial velocity during early filling was comparable between patients and controls. ALL survivors had a significantly longer isovolumetric relaxation time (IVRT). Thirty percent of the ALL survivors have an abnormal IVRT compared to the normal range of the controls. Conclusion and implications for cancer survivors At a median of 13.3 years after exposure to cumulative doses of anthracyclines of 180 or 240 mg/m(2), no clinical relevant cardiotoxicity was found but subclinical cardiac abnormalities were present in 30% of the patients

Low-dose daunorubicin in induction treatment of childhood acute lymphoblastic leukemia:No long-term cardiac damage in a randomized study of the Dutch Childhood Leukemia Study Group

Background. To investigate late cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors after induction treatment with or without daunorubicin (DNR; 25 mg/m(2), i.v., weekly, x4, cumulative dose 100 mg/m(2)). Procedure, Cardiac function was assessed in 90 event-free survivors of childhood ALL, 11.4-17.8 years (median 14.8 years) after treatment according to the DCLSG protocol ALL V. In this protocol patients were randomized to receive (group B) or not to receive (group A) DNR 25 mg/m(2)/week i.v. during the first 4 weeks of induction treatment. Age at diagnosis was 1.2-14.9 years (median 4.5 years). The cardiac evaluation consisted of a history, physical examination, electrocardiogram (ECC), 24 hr ambulatory EGG, and echocardiography. Results. Electrocardiographic data, arrhythmias, left ventricular dimensions, left ventricular contractility, wall stress, and diastolic function were within normal limits in both groups. No difference could be shown between data from group A (n = 40) and group B (n = 50). Conclusions. No late cardiac damage was demonstrated in childhood ALL survivors after induction treatment including a cumulative dose of 100 mg/m(2) DNR, compared to survivors who received the same treatment but without DNR. DNR 100 mg/m(2) given in 4 doses of 25 mg/m(2)/week appears to be a safe dose in induction treatment of ALL. 2000 Wiley-Liss, Inc

Low-dose daunorubicin in induction treatment of childhood acute lymphoblastic leukemia:No long-term cardiac damage in a randomized study of the Dutch Childhood Leukemia Study Group

Background. To investigate late cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors after induction treatment with or without daunorubicin (DNR; 25 mg/m(2), i.v., weekly, x4, cumulative dose 100 mg/m(2)). Procedure, Cardiac function was assessed in 90 event-free survivors of childhood ALL, 11.4-17.8 years (median 14.8 years) after treatment according to the DCLSG protocol ALL V. In this protocol patients were randomized to receive (group B) or not to receive (group A) DNR 25 mg/m(2)/week i.v. during the first 4 weeks of induction treatment. Age at diagnosis was 1.2-14.9 years (median 4.5 years). The cardiac evaluation consisted of a history, physical examination, electrocardiogram (ECC), 24 hr ambulatory EGG, and echocardiography. Results. Electrocardiographic data, arrhythmias, left ventricular dimensions, left ventricular contractility, wall stress, and diastolic function were within normal limits in both groups. No difference could be shown between data from group A (n = 40) and group B (n = 50). Conclusions. No late cardiac damage was demonstrated in childhood ALL survivors after induction treatment including a cumulative dose of 100 mg/m(2) DNR, compared to survivors who received the same treatment but without DNR. DNR 100 mg/m(2) given in 4 doses of 25 mg/m(2)/week appears to be a safe dose in induction treatment of ALL. 2000 Wiley-Liss, Inc

Predicting outcome in children with dilated cardiomyopathy: the use of repeated measurements of risk factors for outcome

Aims: We aimed to determine whether in children with dilated cardiomyopathy repeated measurement of known risk factors for death or heart transplantation (HTx) during disease progression can identify children at the highest risk for adverse outcome. Methods and results: Of 137 children we included in a prospective cohort, 36 (26%) reached the study endpoint (SE: all-cause death or HTx), 15 (11%) died at a median of 0.09 years [inter-quartile range (IQR) 0.03–0.7] after diagnosis, and 21 (15%) underwent HTx at a median of 2.9 years [IQR 0.8–6.1] after diagnosis. Median follow-up was 2.1 years [IQR 0.8–4.3]. Twenty-three children recovered at a median of 0.6 years [IQR 0.5–1.4] after diagnosis, and 78 children had ongoing disease at the end of the study. Children who reached the SE could be distinguished from those who did not, based on the temporal evolution of four risk factors: stunting of length growth (−0.42 vs. −0.02 length Z-score per year, P 6 years at presentation (all P < 0.001) were predictive of adverse outcome. In multivariate analysis, NT-proBNP appeared the only independent predictor for adverse outcome, a two-fold higher NT-proBNP was associated with a 2.8 times higher risk of the SE (hazard ratio 2.78, 95% confidence interval 1.81–3.94, P < 0.001). Conclusions: The evolution over time of NT-proBNP, LVIDd, length growth, and NYU PHFI identified a subgroup of children with dilated cardiomyopathy at high risk for adverse outcome. In this sample, with a limited number of endpoints, NT-proBNP was the strongest independent predictor for adverse outcome