Prevalence and predictors of anthracycline cardiotoxicity in children treated for acute myeloid leukaemia: Retrospective cohort study in a single centre in the United Kingdom

Abstract

Background Anthracycline cardiomyopathy is of concern in children treated for acute myeloid leukaemia (AML), but there are few data on the incidence and natural history of cardiotoxicity after AML treatment in the United Kingdom, where regimens have included high anthracycline exposure. Procedure Prevalence and predictors of cardiotoxicity were retrospectively reviewed in 124 children treated on the MRC AML 10 and AML 12 trials in a single, large centre from November 1987 to September 2004. Subclinical cardiotoxicity was defined as a shortening fraction of less than 28% and clinical cardiomyopathy as evidence of heart failure, and both were classified as late cardiotoxicity 1 year after completing first line therapy. Results Cumulative survival was 61% at 10 years. The prevalence of early and late cardiotoxicity was 13.7% (95%‐CI: 8.2–22.0%) and 17.4% (95%‐CI: 10.9–26.8%), respectively. Early cardiotoxicity was a strong predictor (OR = 9.18; 95%‐CI: 2.10–40.11; P < 0.005) and children who received salvage therapy following relapse showed a trend towards increased late cardiotoxicity (OR = 3.53; 95%‐CI: 0.86–14.48; P < 0.08). Subclinical cardiotoxicity resolved spontaneously in all but one case, but clinical cardiomyopathy always required continuing therapy. Two children died of cardiomyopathy and six remained on medical therapy. Conclusions Anthracycline cardiotoxicity remains a major concern for survivors of childhood AML and correlates with early cardiotoxicity and treatment intensity. Long‐term follow‐up is required to fully determine the outcome for children with subclinical cardiotoxicity. Pediatr Blood Cancer 2011;56:625–630. © 2011 Wiley‐Liss, Inc.

Late cardiomyopathy in childhood acute myeloid leukemia survivors: a study from the L.E.A. program

“…The same feature has already been published by Temming et al who reported a 12% prevalence of late cardiotoxicity after first-line treatment only versus 37% after first-line treatment plus salvage therapy for relapse. 12 The German group also underlined a high risk of late cardiotoxicity in patients who had been treated twice with anthracycline because of secondary AML, which is consistent with our results. 13 In transplanted children, when our study was restricted to patients who never experienced leukemia relapse, we did not detect any difference in late cardiotoxicity between those who received HSCT during their first CR and those treated with chemotherapy only.…”

“…This feature of transient cardiomyopathy occurrence has already been reported in the German as well as in the UK experience of childhood AML survivors' late cardiotoxicity. 12,13 Although potentially reassuring, this concept of possible improvement must be interpreted with caution because long-term persistence of such an improvement cannot be predicted and will require longer follow up. In addition, we cannot exclude the possibility that some apparent improvements were, in fact, due to underestimation of cardiac function in a previous echocardiogram.…”

Evaluation of Cardiotoxicity by Tissue Doppler Imaging in Childhood Leukemia Survivors Treated with Low-Dose Anthracycline

“…More recent studies that included both the LV and RV reported functional deterioration also at RV [12,14]. It was recently reported that diastolic dysfunction can precede systolic dysfunction and the risk of diastolic dysfunction in RV is higher than that of LV [14,25]. In contrast, another recent study reported normal RV function and high LV MPI values in patients with early-stage anthracycline-induced cardiotoxicity [4].…”

The Combination of Fludarabine, Cytarabine and Etoposide Is an Active and Well-Tolerated Regimen in Relapsed/Refractory Acute Myeloid Leukemia

“…Analysis from two pediatric AML studies (MRC AML10 and AML12) showed a prevalence of early and late cardiotoxicity of 14 and 17%, respectively, and there was a trend toward increased cardiotoxicity in patients who subsequently received salvage therapy [31]. In another pediatric analysis that included 1,207 AML patients <18 years of age treated in trials AML-BFM93/98, the cumulative incidence of cardiotoxicity at 11 years was 5% [32].…”