Daunorubicin cardiac toxicity in children with acute lymphocytic leukemia

Abstract

Daunorubicin (DNR) cardiac toxicity was documented in 17 (9.9%) of 172 children with acute lymphocytic leukemia. Group IIB (7/87) received twice weekly methotrexate (MTX) and pulse dose of vincristine, DNR, and prednisone (Pred). Group IIIB (10/85) received methotrexate (MTX), 6-MP, and the same pulse dose. Groups IIA, 88 patients, and IIIA, 79 patients, were treated similarly to IIB and IIIB, but without DNR. The latter were all free of cardiac toxicity. This is the first random controlled study to demonstrate DNR cardiotoxicity. The 17 children were in complete remission at onset of cardiac symptoms. The range of DNR administered was 360-1260 mg/m2. All 17 patients had onset of congestive heart failure that responded well initially to anticongestive treatment. Electrocardiograms were abnormal showing a variety of changes. In three patients, systolic time intervals indicated severe myocardial dysfunction. Postmortem cardiac studies on two patients demonstrated myocardial interstitial edema with cellular degeneration manifested by irregularity and separation and loss of some myofibrils. DNR demonstrated no advantage as a supplement to VCR and Pred reinforcement with regard to remission duration. DNR used in this described schedule causes significant and debilitating cardiac toxicity in 10% of patients treated.