Cardiovascular disease after childhood acute lymphoblastic leukaemia: a cohort study.

Roland A Ammann,Nicolas X Von Der Weid,Julien N Caccia,Claudia E Kuehni,Rahel Kasteler,Ben Spycher,Eva M Hau,Thomas Suter

doi:10.4414/smw.2019.20012

Abstract

Cardiovascular diseases (CVD) increase late morbidity and mortality in survivors of acute lymphoblastic leukaemia (ALL). We compared the risk of CVD in ALL survivors to siblings, examined time trends, quantified treatment-related risks, and investigated whether risk extends beyond patients treated with anthracyclines and chest radiotherapy. The Swiss Childhood Cancer Survivor Study assessed CVD by patient questionnaire in 5-year ALL survivors diagnosed between 1976 and 2005 and their siblings. Participants were asked whether a physician had ever told them that they had hypertension, arrhythmia, heart failure, myocardial infarction, angina pectoris, stroke, thrombosis or valvular problems. We investigated treatment-related risk factors for CVD using multivariable logistic regression, adjusting for demographic and socioeconomic factors, BMI, smoking, diabetes mellitus, alcohol consumption and physical activity. We contacted 707 survivors and 1299 siblings, 511 (72%) and 709 (55%) of whom responded, respectively. Survivors had a higher risk of developing CVD than siblings (odds ratio [OR] 1.9, 95% confidence interval 1.3–2.8), in particular heart failure (OR 13.9, 1.8–107.4). Compared to patients treated 1976–85, the risk of CVD was 1.4 (0.7–2.8) for those treated 1985–1994 and 1.5 (0.6–3.7) for those treated 1995–2005. The overall CVD risks after anthracycline treatment (OR 3.1, 2.0–4.7), haematopoietic stem cell transplantation (OR 8.0, 2.4–26.9) or relapse (OR 4.1, 1.9–8.8) were increased compared to those of siblings, while the CVD risks of survivors treated without anthracycline or chest radiotherapy were similar (OR 1.0; 0.5–2.0). Despite attempts to reduce cardiotoxicity in childhood cancer treatment, CVD risks in ALL survivors treated more recently do not seem to have declined.

Highlights

Acute lymphoblastic leukaemia (ALL) is the most common malignancy in childhood
The overall cardiovascular diseases (CVD) risks after anthracycline treatment, haematopoietic stem cell transplantation or relapse were increased compared to those of siblings, while the CVD risks of survivors treated without anthracycline or chest radiotherapy were similar
(analysis 3), we investigated differences in CVD risk according to treatment-related risk factors

Summary

Introduction

Acute lymphoblastic leukaemia (ALL) is the most common malignancy in childhood. Its incidence has increased in recent decades [1]. A consequence of these effective treatments is damage to normal tissues, which may result in the long-term dysfunction of many organs. The cardiovascular system is vulnerable to cancer treatment, and cardiovascular diseases (CVD) are recognised late effects of cancer treatment [3]. Survivors of childhood ALL have a lifelong increased risk for cardiovascular morbidity and mortality compared to the general population, mainly caused by chemotherapy with anthracyclines or, to a lesser extent, by direct or scattered chest radiotherapy [4]. ALL survivors have an increased prevalence of insulin resistance and dyslipidaemia [5], and differ from their siblings in health behaviours relevant for CVD, such as physical activity, smoking and alcohol consumption [6,7,8,9]

Methods

Results

Conclusion