Dexrazoxane significantly reduced the risk of left ventricular systolic dysfunction by 45% (HR 0.55) compared to no dexrazoxane in pediatric patients with acute myeloid leukemia.
Cohort (n=1,014)
Yes
Does dexrazoxane prevent left ventricular systolic dysfunction in pediatric patients with acute myeloid leukemia receiving anthracycline-based chemotherapy?
Dexrazoxane provides effective cardioprotection against anthracycline-induced left ventricular systolic dysfunction in pediatric AML without compromising survival or increasing noncardiac toxicities.
Effect estimate: HR 0.55 (95% CI 0.36-0.86)
Absolute Event Rate: 26.5% vs 42.2%
p-value: p=0.009
PURPOSE To determine whether dexrazoxane provides effective cardioprotection during frontline treatment of pediatric acute myeloid leukemia (AML) without increasing relapse risk or noncardiac toxicities of the chemotherapy regimens. PATIENTS AND METHODS This was a multicenter study of all pediatric patients with AML without high allelic ratio FLT3/ITD treated in the Children’s Oncology Group trial AAML1031 between 2011 and 2016. Median follow-up was 3.5 years. Dexrazoxane was administered at the discretion of treating physicians and documented at each course. Ejection fraction (EF) and shortening fraction (SF) were recorded after each course and at regular intervals in follow-up. Per protocol, anthracyclines were to be withheld if there was evidence of left ventricular systolic dysfunction (LVSD) defined as SF < 28% or EF < 55%. Occurrence of LVSD, trends in EF and SF, 5-year event-free survival (EFS) and overall survival (OS), and treatment-related mortality (TRM) were compared by dexrazoxane exposure. RESULTS A total of 1,014 patients were included in the analyses; 96 were exposed to dexrazoxane at every anthracycline course, and 918 were never exposed. Distributions of sex, age, race, presenting WBC count, risk group, treatment arm, and compliance with cardiac monitoring were similar for dexrazoxane-exposed and -unexposed patients. Dexrazoxane-exposed patients had significantly smaller EF and SF declines than unexposed patients across courses and a lower risk for LVSD (26.5% v 42.2%; hazard ratio, 0.55; 95% CI, 0.36 to 0.86; P = .009). Dexrazoxane-exposed patients had similar 5-year EFS (49.0% v 45.1%; P = .534) and OS (65.0% v 61.9%; P = .613) to those unexposed; however, there was a suggestion of lower TRM with dexrazoxane (5.7% v 12.7%; P = .068). CONCLUSION Dexrazoxane preserved cardiac function without compromising EFS and OS or increasing noncardiac toxicities. Dexrazoxane should be considered for cardioprotection during frontline treatment of pediatric AML.
Getz et al. (Tue,) conducted a cohort in Pediatric acute myeloid leukemia (n=1,014). Dexrazoxane vs. No dexrazoxane was evaluated on Left ventricular systolic dysfunction (LVSD) defined as SF < 28% or EF < 55% (HR 0.55, 95% CI 0.36-0.86, p=0.009). Dexrazoxane significantly reduced the risk of left ventricular systolic dysfunction by 45% (HR 0.55) compared to no dexrazoxane in pediatric patients with acute myeloid leukemia.