N-Terminal-ProB-Type Natriuretic Peptide as a Marker for Anthracycline Cardiotoxicity in Children with Acute Lymphoblastic Leukaemia

Background: Anthracyclines (ANTR) are very effective agents in treatment of acute lymphoblastic leukaemia (ALL). However, a potential heart damage caused by ANTR in patients who have been cured of ALL may lessen the success of this cure. Plasma brain B-type natriuretic peptide (BNP) levels are highly sensitive biochemical markers for myocardial damage.

Objectives of the study: Our purpose was to evaluate N-terminal proBNP (Nt-proBNP) as a screening test for detecting cardiac dysfunction in children with ALL.

Subjects: 156 asymptomatic children (72 girls and 84 boys) who had received ANTR during treatment for ALL were evaluated. They had received ANTR doses of 180 to 480mg/m² (according to the protocol treatment) at median age of 6.6 years at diagnosis. 47 healthy children constituted the control group.

Methods: Concentration of plasma N-terminal proBNP was measured in 420 samples by enzyme immunoassay (Biomedica) before treatment, after 6 months, 2 and 4 years and longer than 5 years after ANTR therapy. 261 echocardiograms (ECHO) were performed in 128 children. Nt-proBNP was measured at the same time. Shortening fraction (%SF) and ejection fraction (%EF) were determined as systolic left ventricular function.

Results: Mean Nt-proBNP plasma levels in children with ALL were higher in comparison with the control group (90.7 and 66.2pg/ml respectively) but the difference was not significant (p=0.2). The levels of Nt-proBNP before ALL treatment were significantly the lowest (51.5pg/ml). Later, they were respectively: 108.3pg/ml after 6 months, 97.4pg/ml after 2 years and 92.9pg/ml after 4 years (p=0.0019). The highest levels of NT-proBNP were observed in children with cumulative ANTR doses of 240, 330 and 480mg/m² (98.8pg/ml, 102.8pg/ml, 86.1pg/ml respectively) (p=0.0008). The lowest levels were observed with the cumulative doses of 180mg/m² and 300mg/m² (60.7pg/ml and 58.8pg/ml respectively). The average value of %SF in children with ALL was 39.4% (26 to 52%) and the average value of %EF was 69.95% (51.1 do 83.4%). In children with %SF and %EF lower than the average in both study and control group Nt-proBNP was insignificantly higher than in children whose %SF and %EF were higher than the average in both groups (respectively for %SF: 107.1pg/ml and 97.3pg/ml and for %EF: 106.3pg/ml and 98.8pg/ml).

Conclusion: Increased Nt-proBNP levels were observed more often in children who received higher doses of ANTR and in all children after the end of treatment. Independently of ECHO assessment of the left ventricular function, the Nt-proBNP is of value in the detection of subclinical left ventricular dysfunction in children with ALL who were treated with ANTR therapy.