Acute cardiotoxicity of idarubicin in patients treated for hematological malignancy

Konference: 2006 2. ročník Dny diagnostické, prediktivní a experimentální onkologie

Kategorie: Toxicita, nežádoucí účinky léčby

Téma: Postery

Číslo abstraktu: 008p

Autoři: MUDr. Jan Horáček, Ph.D.; Prof. RNDr. Miloš Tichý, CSc.; Prof.MUDr. Radek Pudil, Ph.D.; Mjr. doc. MUDr. Ladislav Slováček, Ph.D.

Background: Cardiotoxicity is a serious and relatively frequent complication of antitumorous treatment. Anthracyclines represent the greatest risk. Various methods have been recommended for cardiotoxicity monitoring. Biochemical markers of structural and functional myocardial injury have been gaining ground in this field.
Aim: Monitoring of acute cardiac toxicity during induction chemotherapy for acute myeloid leukemia (AML) and assessment of the potential for use of biochemical markers in early diagnostics of cardiotoxicity.
Methods: Fifteen consecutive adult patients with a newly diagnosed AML (mean age 43.7± 10.6 years, 9 male and 6 female) were studied. The patients received induction chemotherapy containing intermediate doses of cytarabine and anthracycline agent – idarubicin (IDA) 12mg/m2/day intravenously on day 1, 3 and 5 (in total 36mg/m2 = one quarter of the maximum recommended cumulative dose).
From biochemical markers of myocardial injury, we used N-terminal pro brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT) and creatine kinase MB (CK-MB mass). Serial measurements of plasma NT-proBNP concentrations were performed at the baseline, the day following each IDA infusion, after 14 days and after circa 1 month, i.e. before the next chemotherapy. Cardiospecific markers (cTnT, CK-MB mass) were measured at the baseline and after the last IDA infusion.
Results: The mean baseline concentration of NT-proBNP in newly diagnosed AML patients was 129.7 ± 59.6 pg/ml. The mean NT-proBNP concentration increased after the first IDA infusion to 307.3 ± 171.4 pg/ml (p < 0.05). In most of the patients, the second and the third IDA infusions were not associated with a further increase in the NT-proBNP value and values after 2 or 4 weeks were not significantly different from the baseline. However, in one of the patients the NT-proBNP values were increasing after each IDA infusion (after the last one 786.2pg/ml) and within 14 days he developed congestive heart failure due to left ventricular diastolic dysfunction as assessed by echocardiography. At that time, the NT-proBNP value was 1184.0pg/ml; after diuretics it decreased significantly.
In all patients, plasma cTnT and CK-MB mass concentrations were within the reference interval at the baseline and after the induction chemotherapy.
Conclusions: Our results show that induction chemotherapy in AML (IDA 36mg/m2 and intermediate doses of cytarabine):
  1. does not cause detectable damage of cardiomyocyte structure
  2. is in most patients associated with acute neurohumoral activation (transient elevation of NTproBNP) indicating acute subclinical cardiotoxicity
  3. may lead to congestive heart failure and NTproBNP seems to be a promising early marker and predictor of this complication.

Further follow-up of the patients is required to find out whether these acute changes are predictive for chronic and late anthracycline cardiotoxicity.

The work was primarily supported by the Research Project MO 0FVZ 0000 503.

Datum přednesení příspěvku: 7. 12. 2006