title: Assessment of late cardiotoxicity of pirarubicin (THP) in children with acute lymphoblastic leukemia.
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).
  
  
  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.
authors.affiliation: Department of Pediatrics, Aichi Medical University, Aichi-gun, Aichi-ken, Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Reizo
authors.initials: R
authors.lastname: Baba
authors.forename: Arata
authors.initials: A
authors.lastname: Watanabe
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Horikoshi
authors.forename: Keiko
authors.initials: K
authors.lastname: Asami
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hyakuna
authors.forename: Asayuki
authors.initials: A
authors.lastname: Iwai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yamaji
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hori
authors.forename: Masahito
authors.initials: M
authors.lastname: Tsurusawa
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents; D002648:Child; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004562:Electrocardiography; D006331:Heart Diseases / Q000139:chemically induced; D006334:Heart Function Tests; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy*; D017741:Survivors; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D004317:Doxorubicin; C027260:pirarubicin