04 May 2020

Children receiving chemotherapy for acute myeloid leukaemia (AML) could benefit from taking the drug dexrazoxane to protect their heart, US doctors have reported.

Anthracyclines are a key component of chemotherapy for paediatric AML. However, children receiving anthracyclines are at increased risk of early- and late-cardiotoxicity, including left ventricular systolic dysfunction (LVSD). Currently, at least 12% of AML patients experience LVSD within a year of starting treatment

A new observational study looked at the outcomes of 1,092 paediatric acute myeloid leukaemia patients previously enrolled in the AAML1031 trial between 2011 and 2016, some of whom had received dexrazoxane to protect heart function. Of these patients, 84% were never exposed to dexrazoxane, and 9% received it with all their anthracycline chemotherapy. The remaining 7% were given it at some of their treatments and were excluded from the analysis.

Although the allocation of dexrazoxane was not randomised, patient demographic and clinical characteristics were similar between patients who had received dexrazoxane throughout their chemotherapy and those who had not.

The analysis concluded that dexrazoxane significantly reduce risk of LVSD in these patients. Of those who had received dexrazoxane throughout their chemotherapy treatment, 27% developed LVSD, compared with 42% of those who did not have the drug at all.

Treatment-related mortality was 6% with the drug and 13% without, although this difference was not statistically significant. Five-year event free survival and overall survival rates were similar in both groups, according to the report in the Journal of Clinical Oncology.

The team, led by researchers from Children’s Hospital of Philadelphia, USA, suggest that dexrazoxane should be considered for all paediatric patients undergoing standard chemotherapy for AML.

Researcher Prof Richard Aplenc said: “This study provides important evidence that using dexrazoxane helps prevent heart damage in children undergoing treatment for acute myeloid leukaemia. These results have arguably changed the standard of care for paediatric acute myeloid leukaemia treatment.”

First author, Dr Kelly Getz, added: “Additional research to understand the underlying biology of anthracycline-associated cardiotoxicity and effective interventions will improve both the cardiovascular and oncologic outcomes for children with cancer.”

Source: Getz KD, Sung L, Alonzo TA, Leger KJ, Gerbing RB, Pollard JA, Cooper T, Kolb EA, Gamis AS, Ky B, Aplenc R (2020) “Effect of dexrazoxane on left ventricular systolic function and treatment outcomes in patients with acute myeloid leukemia: a report from the Children's Oncology Group”, Journal of Clinical Oncology, doi: 10.1200/JCO.19.02856


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