Impact of preparative regimen and haematopoietic stem cell transplantation on circulating markers of cardiac damage

Overview

Introduction:
Cardiac toxicity is a relatively frequent and potentially serious complication of treatment in hematooncology. Anthracyclines and high-dose chemotherapy represent the greatest risk. Various methods including measurement of circulating markers have been recommended for monitoring of cardiotoxicity of oncology treatment.

Aim:
Assessment of cardiotoxicity during preparative regimen (PR) and haematopoietic stem cell transplantation (HSCT) in acute leukemia (AL) with circulating markers – N-terminal pro brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT) and creatine kinase MB (CK-MB mass).

Patients and methods:
Nineteen adult patients treated for AL (mean age 42.8±10.0 years, 13 males) were studied. The patients were pretreated with anthracyclines in the cumulative dose (CD) of 446.1±91.6 mg/m². PR consisted of high-dose Cyclophosphamide 120 mg/kg (HD-C) and Busulphan 16 mg/kg in 13 patients, HD-C and fractionated total body irradiation 12 Gy (TBI) in 6 patients. Ten patients underwent allogeneic HSCT, 9 patients autologous HSCT. Plasma NT-proBNP, cTnT and CK-MB mass concentrations were measured the day before PR, the day after PR, the day after HSCT and 14 days after HSCT, i.e. at the time of bone marrow recovery.

Results:
The day before PR, mean plasma NT-proBNP value was 106.3±55.7 pg/ml (slightly elevated in 4 patients). The mean NT-proBNP increased to 426.1±391.5 pg/ml after completion of PR. After HSCT, a further increase to 847.6±780.6 pg/ml was observed. Fourteen days after HSCT, the mean NTproBNP was 330.8±236.8 pg/ml, values remained elevated in 12 patients. The differences were statistically significant in comparison with the baseline NT-proBNP (p < 0.01). The NT-proBNP elevations were more pronounced in patients with CD of anthracyclines above 450 mg/m² (p < 0.05), in patients with PR containing HD-C and TBI (p<0.05) and in patients undergoing allogeneic HSCT (p < 0.05). In all patients, plasma cTnT and CK-MB mass concentrations remained negative during PR and HSCT.

Conclusions:
Our results suggest that administration of PR and HSCT is in most AL patients associated with acute neurohumoral activation (significant rise in NT-proBNP). Persistent NT-proBNP elevations, in our study in 12 (63.2 %) patients, indicate subclinical cardiotoxicity (risk for

development of heart failure) and require further follow-up. More pronounced NT-proBNP elevations in patients with higher CD of anthracyclines and in patients with PR containing combination of high-dose chemotherapy and radiotherapy confirm that these therapeutic procedures seem to be more cardiotoxic and not very appropriate for patients with cumulation of risk factors for cardiotoxicity. Negative plasma cTnT and CK-MB mass concentrations show no detectable damage of cardiomyocyte structure during PR and HSCT.

Key words:
cardiotoxicity, circulating markers, preparative regimen, transplantation, acute leukemia