Assessment of late cardiotoxicity of pirarubicin (THP) in children with acute lymphoblastic leukemia

Pediatr Blood Cancer. 2011 Sep;57(3):461-6. doi: 10.1002/pbc.23012. Epub 2011 Feb 4.

Abstract

Background: Pirarubicin (tetrahydropyranyl-adriamycin: THP) is a derivative of doxorubicin with reportedly less cardiotoxicity in adults. However no studies of cardiotoxicity in children treated with THP have been reported. This study was performed to assess the THP-induced cardiotoxicity for children with acute lymphoblastic leukemia (ALL).

Patients and methods: This study comprised 61 asymptomatic patients aged from 7.6 to 25.7 years old. Median follow-up time after completion of anthracycline treatment was 8.1 years (range: 1.7-12.5). The cumulative dose of THP ranged from 120 to 740 mg/m(2) with a median of 180 mg/m(2) . Patients underwent electrocardiogram (ECG), echocardiography, the 6-min walk test (6MWT), and measurements of serum brain natriuretic peptide (BNP) before and after exercise.

Results: All subjects showed normal left ventricular function assessed by echocardiography. Ventricular premature contraction in Holter ECG and reduced exercise tolerance in the 6MWT were detected in 2/46 (3.3%) and 5/41(12.2%), respectively. Abnormal BNP levels were detected in 6/60 (10%) both before and after exercise. The cumulative dose of THP was significantly correlated with BNP levels after exercise (r = 0.27, P = 0.03), but not with any other cardiac measurements. Further analysis revealed that subjects with a high cumulative dose ≧300 mg/m(2) had significantly higher BNP levels after exercise compared with subjects with a low cumulative dose <300 mg/m(2) (P = 0.04).

Conclusions: No significant cardiac dysfunction was detected in long-term survivors who received THP treatment. The use of post-exercise BNP level to indicate high cardiotoxicity risk should be verified by further study.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Anthracyclines / therapeutic use
  • Antineoplastic Agents
  • Child
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / toxicity
  • Electrocardiography
  • Heart Diseases / chemically induced
  • Heart Function Tests
  • Humans
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Survivors
  • Young Adult

Substances

  • Anthracyclines
  • Antineoplastic Agents
  • Doxorubicin
  • pirarubicin