Myocardial performance index and biochemical markers for early detection of doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukaemia.
BACKGROUND
Despite significant improvements in the prognosis of childhood acute lymphoblastic leukaemia (ALL), the risk of anthracycline-induced cardiovascular disease remains a major concern. This study was designed to investigate the role of the myocardial performance index (MPI) and serum concentrations of biomarkers (cTnT and NT-pro-BNP) in the early detection of subclinical anthracycline-induced functional alterations in children with ALL.


METHODS
All children consecutively admitted to our Pediatric Oncologic Department from January 2009 to October 2010 with a diagnosis of ALL were enrolled in this study. cTnT and NT-pro-BNP were evaluated in all patients at diagnosis, before doxorubicin therapy and 2 and 24 h following each anthracycline administration. ECG and echocardiography were performed at diagnosis and 24 h after each anthracycline course.


RESULTS
Nineteen children with standard-risk ALL were evaluated. The mean age was 6 years. The cumulative doxorubicin dosage was 240 mg/m(2) according to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) ALL 2000 protocol. None of the 19 patients developed congestive heart failure. With increasing cumulative dosages of anthracyclines a significant increase was observed in MPI. This increase was statistically significant starting from the cumulative dosage of 120 mg/m(2) compared to baseline, while the median NT-pro-BNP level did not change significantly during treatment and cTnT levels never exceeded the cut-off value for cardiac injury.


CONCLUSIONS
MPI value is a sensitive and accurate parameter, allowing subclinical cardiac dysfunction to be detected in children receiving anthracyclines. Lifelong cardiac surveillance of these patients is warranted in order to determine the clinical implications of increased MPI on long-term cardiac status.
Pediatric Oncology Division, "A. Gemelli" Hospital, Catholic University of Rome, Largo A Gemelli, 1, 00168, Rome, Italy, ruggiero@rm.unicatt.it.
Antonio
A
Ruggiero
Gabriella
G
De Rosa
Daniela
D
Rizzo
Andrea
A
Leo
Palma
P
Maurizi
Alessia
A
De Nisco
Francesca
F
Vendittelli
Cecilia
C
Zuppi
Alvaro
A
Mordente
Riccardo
R
Riccardi
D054715:Cardiotoxins / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004317:Doxorubicin / Q000009:adverse effects*; D042241:Early Diagnosis; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D019209:Troponin C / Q000097:blood
D054715:Cardiotoxins; D010446:Peptide Fragments; D019209:Troponin C; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D004317:Doxorubicin