Annals of Oncology Advance Access originally published online on July 11, 2008
Annals of Oncology 2008 19(9):1656-1657; doi:10.1093/annonc/mdn414
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letters to the editor |
Glycogen phosphorylase BB could be a new circulating biomarker for detection of anthracycline cardiotoxicity
Chemotherapy (CT)-induced cardiotoxicity remains a topical problem in cancer survivors. Anthracyclines represent the greatest risk for development of cardiotoxicity [1]. Various methods including cardiac biomarkers have been recommended for monitoring of cardiotoxicity in oncology. The clinical studies using cardiac troponins for evaluation of anthracycline-induced cardiotoxicity brought inconsistent results [2–4]. In our previous study, we, as the first, applied new biomarkers of cardiac injury—glycogen phosphorylase BB (GPBB) and heart-type fatty acid-binding protein (H-FABP)—in the assessment of cardiac toxicity during high-dose CT followed by hematopoietic cell transplantation [5]. In our current study, we evaluated acute and chronic cardiotoxicity of anthracyclines with multiple biomarkers of cardiac injury: GPBB, H-FABP, cardiac troponin I (cTnI), cardiac troponin T (cTnT), creatine kinase MB (CK-MB mass) and myoglobin. GPBB and H-FABP have not been studied in this setting so far.Twenty-four patients with de novo acute myeloid leukemia (mean age 48.1 ± 10.9 years, 13 males) treated with three to six cycles of anthracycline-based CT were studied. All patients had normal liver and renal functions during the study. Circulating biomarkers of cardiac injury were measured on Evidence Randox (GPBB, FABP, cTnI) and Elecsys Roche (cTnT, CK-MB mass, myoglobin) analyzers at the baseline, the day after first CT with anthracyclines (mean cumulative dose 130.6 ± 29.8 mg/m2), the day after last CT containing anthracyclines (mean total cumulative dose 463.2 ± 114.3 mg/m2) and 6 months after completion of treatment. Values above the reference range on the basis of a number of cardiology studies and recommended by the manufacturers were considered elevated. The cut-off values for cardiac injury were as follows: 7.30 µg/l for GPBB, 4.50 µg/l for H-FABP, 0.40 µg/l for cTnI, 0.01 µg/l for cTnT, 4.80 µg/l for CK-MB mass and 76.0 µg/l for myoglobin.
GPBB increased above the cut-off (7.30 µg/l) in four (16.7%) patients after first CT, in five (20.8%) patients after last CT and remained elevated in five (20.8%) patients within 6 months after CT. CTnI became elevated (>0.40 µg/l) in two (8.3%) patients after first and last CT and was elevated in three (12.5%) patients within 6 months after CT. CTnT remained negative (<0.01 µg/l) during CT in all patients. Six months after CT, delayed cTnT positivity was found in two (8.3%) patients. All patients with cTnI or cTnT positivity had elevated GPBB. Other tested biomarkers (myoglobin, CK-MB mass, H-FABP) remained within the reference range in all patients.
Our results indicate that GPBB could be a new promising biomarker for detection of anthracycline-induced cardiotoxicity and probably superior to cardiac troponins. The predictive value for development of cardiomyopathy in the future is not known and will be evaluated during a prospective follow-up. A larger prospective and multicenter study will be needed to confirm our preliminary results and define the potential role of new circulating biomarkers in the assessment of anthracycline-induced cardiotoxicity.
funding
MO 0FVZ 0000503 (Czech Ministry of Defence) and MZO 00179906 (Czech Ministry of Health).
1 Second Department of Medicine–Clinical Hematology, Hradec Kralove, Czech Republic
2 Institute of Clinical Biochemistry and Diagnostics, Hradec Kralove, Czech Republic
3 First Department of Medicine, University Hospital and Charles University, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic
4 Department of Internal Medicine, University of Defence, Faculty of Military Health Sciences in Hradec Kralove, Czech Republic
* (E-mail: jan.hor{at}post.cz)
References
1. Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med (1996) 125:47–58.
2. Kismet E, Varan A, Ayabakan C, et al. Serum troponin T levels and echocardiographic evaluation in children treated with doxorubicin. Pediatr Blood Cancer (2004) 42:220–224.[CrossRef][Web of Science][Medline]
3. Kilickap S, Barista I, Akgul E, et al. CTnT can be a useful marker for early detection of anthracycline cardiotoxicity. Ann Oncol (2005) 16:798–804.
4. Wallace KB, Hausner E, Herman E, et al. Serum troponins as biomarkers of drug-induced cardiac toxicity. Toxicol Pathol (2004) 32:106–121.
5. Horacek JM, Tichy M, Jebavy L, et al. Glycogen phosphorylase BB as a marker of cardiac toxicity during high-dose chemotherapy followed by hematopoietic cell transplantation. Ann Oncol (2007) 18:2041.
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