Administration of Dexrazoxane Improves Cardiac Indices in Children and Young Adults With Acute Myeloid Leukemia (AML) While Maintaining Survival Outcomes

Abstract

Anthracycline induced cardiotoxicity remains a significant contributor to late morbidity/mortality in children and young adults with acute myeloid leukemia (AML). The cardioprotectant dexrazoxane can be used as prophylaxis to diminish risk for cardiomyopathy but whether it affects risk of relapse in pediatric AML is unclear. Our institution adopted the use of dexrazoxane prior to anthracyclines administration for all oncology patients in 2011. We compared patients with AML (ages 0 to 21 years) who received or did not receive dexrazoxane during the years 2008 to 2013. Forty-four patients with AML (ages 4.5 months to 21.7 years) were included. We identified no statistical difference in 2-year event rate (62% vs. 50%, p=0.41) or 2-year overall survival (OS) (69% vs. 69%, p=0.53) between patients receiving (n=28) or not receiving (n=16) dexrazoxane. Ejection fraction (p=0.0262) and shortening fraction (p=0.0381) trended significantly higher in patients that received dexrazoxane compared to those that did not receive dexrazoxane. Utilization of the cardioprotectant dexrazoxane prior to anthracycline chemotherapy in pediatric patients with AML demonstrated no significant difference in either event rate or OS relative to institutional controls and appears to improve cardiac function indices. Further studies in this patient population are needed to confirm these findings.

Risk–Benefit of Dexrazoxane for Preventing Anthracycline-Related Cardiotoxicity: Re-Evaluating the European Labeling

“…The underlying cause of death in these four patients was the original tumor DRZ is not associated with deaths from cardiovascular causes The increases in cTnT were associated with abnormally reduced LV mass and end-diastolic posterior wall thickness after 4 years (p Ͻ 0.01). Increases in NT-proBNP were related to abnormal LV thickness-to-dimension ratio after 4 years (p = 0.01) [11] Retrospective AML Ͻ21 years old Anthracycline (n = 16) alone or combined with DRZ (n = 28) EF (p = 0.03) and shortening fraction z-scores (p = 0.04) were significantly higher in DRZ patients than patients treated with chemotherapy alone [13] † Dose ratio DRZ:anthracycline. ‡ Results from the P9754 trial were also included in the abstract.…”

“…When we limited the results to publications consistent with the revised label for Cardioxane, 13 clinical trials [6][7][8][9][10][11][12][13][14][15][16][17][18] and four meta-analyses or systematic reviews remained [19][20][21][22]. These meta-analyses and systematic…”

Pharmacogenetics of Chemotherapy-Induced Cardiotoxicity

“…Interestingly, cardiomyocytes do not express topoisomerase IIα like tumor cells, but topoisomerase IIβ which can similarly complex with anthracyclines and result in cell death and decreased mitochondrial biogenesis [10, 11]. This is important because dexrozaxane is a cardioprotectant that has been shown to decrease incidence and severity of cardiotoxicity from anthracycline exposure [12–14] and acts through inhibition of both isomers of topoisomerase II as well as by chelating free iron and decreasing free radical generation [15–17]. …”

Early markers of cardiovascular injury in childhood leukaemia survivors treated with anthracycline chemotherapy

“…Additionally, it is rare to see cMRI studies that utilise matched control groups. Leukaemia is the most common childhood cancer, with its survivors representing one of the largest cohorts at risk of, or currently experiencing, the various complications of late anthracycline toxicity [8,[20][21][22][23]. Despite this, it has not yet been determined whether cMRI with late gadolinium enhancement is able to detect signs of underlying anthracycline injury in this survivorship group.…”