Cardiac Biomarkers May Predict Toxicity During Doxorubicin Treatment in Children with High-Risk ALL

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(ChemotherapyAdvisor) – The cardiac injury biomarker cardiac troponin (cTnT) and the cardiomyopathy biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) may hold promise as biomarkers of cardiotoxicity in children with high-risk acute lymphoblastic leukemia (ALL) during treatment with doxorubicin, according to a study published in the Journal of Clinical Oncology online February 27.

Children with high-risk ALL were randomly assigned to receive doxorubicin alone (n=100; 75 analyzed) or doxorubicin with dexrazoxane (n=105; 81 analyzed). Echocardiograms and serial serum measurements of cTnT, NT-proBNP, and the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) were obtained before, during, and after treatment.

Prior to treatment, levels of cTnT were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group and in 47% and 13%, respectively, after treatment. Levels of NT-proBNP were increased in 89% of children in the doxorubicin group and in 92% of children in the doxorubicin-dexrazoxane group before treatment but in only 48% and 20%, respectively, after treatment. Percentage of children with increased hsCRP levels did not differ between groups at any time point.

Detectable increases in cTnT in the first 90 days of treatment were associated with abnormally reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness four years later. Increases in NT-proBNP were related to an abnormal LV thickness-to-dimension ratio, suggesting LV remodeling four years later. HsCRP increases were not associated with any echocardiographic variables.

The authors concluded that definitive validation studies are required to establish a range of clinical utility for these cardiac biomarkers.


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