Publisher's Note: There is an Inside Blood Commentary on this article in this issue.

Gardner et al report that early intervention with tocilizumab and steroids at the first signs of mild cytokine release syndrome (CRS) following CD19 chimeric antigen receptor (CAR) T-cell infusion for B-cell acute lymphocytic leukemia reduces the development of life-threatening severe CRS without having a negative impact on antileukemic effect.

Purpose Late cardiotoxicity after pediatric acute myeloid leukemia therapy causes substantial morbidity and mortality. The impact of early-onset cardiotoxicity on treatment outcomes is less well understood. Thus, we evaluated the risk factors for incident early cardiotoxicity and the impacts of cardiotoxicity on event-free survival (EFS) and overall survival (OS). Methods Cardiotoxicity was ascertained through adverse event monitoring over the course of follow-up among 1,022 pediatric patients with acute myeloid leukemia treated in the Children’s Oncology Group trial AAML0531. It was defined as grade 2 or higher left ventricular systolic dysfunction on the basis of Common Terminology Criteria for Adverse Events (version 3) definitions. Results Approximately 12% of patients experienced cardiotoxicity over a 5-year follow-up, with more than 70% of incident events occurring during on-protocol therapy. Documented cardiotoxicity during on-protocol therapy was significantly associated with subsequent off-protocol toxicity. Overall, the incidence was higher among noninfants and black patients, and in the setting of a bloodstream infection. Both EFS (hazard ratio [HR], 1.6; 95% CI, 1.2 to 2.1; P = .004) and OS (HR, 1.6; 95% CI, 1.2 to 2.2, P = .005) were significantly worse in patients with documented cardiotoxicity. Impacts on EFS were equivalent whether the incident cardiotoxicity event occurred in the absence (HR, 1.6; 95% CI, 1.1 to 2.2; P = .017) or presence of infection (HR, 1.6; 95% CI, 1.0 to 2.7; P = .069) compared with patients without documented cardiotoxicity. However, the reduction in OS was more pronounced for cardiotoxicity not associated with infection (HR, 1.7; 95% CI, 1.2 to 2.5; P = .004) than for infection-associated cardiotoxicity (HR, 1.3; 95% CI, 0.7 to 2.4; P = .387). Conclusion Early treatment-related cardiotoxicity may be associated with decreased EFS and OS. Cardioprotective strategies are urgently needed to improve relapse risk and both short- and long-term mortality outcomes.

With 5-year survival of children with cancer exceeding 80% in developed countries, premature cardiovascular disease is now a major cause of early morbidity and mortality. In addition to the acute and chronic cardiotoxic effects of anthracyclines, related chemotherapeutics, and radiation, a growing number of new molecular targeted agents may also have detrimental effects on the cardiovascular system. Survivors of childhood cancer also may have earlier development of conventional cardiovascular risk factors such as hypertension, dyslipidaemia, and diabetes, which further increase their risk of serious cardiovascular disease. This review will examine the epidemiology of acute and chronic cardiotoxicity relevant to paediatric cancer patients, including genetic risk factors. We will also provide an overview of current screening recommendations, including the evidence regarding both imaging (e.g. echocardiography and magnetic resonance imaging) and blood-based biomarkers. Various primary and secondary prevention strategies will also be discussed, primarily in relation to anthracycline-related cardiomyopathy. Finally, we review the available evidence related to the management of systolic and diastolic dysfunction in paediatric cancer patients and childhood cancer survivors.