Annals of Oncology Advance Access originally published online on October 31, 2007
Annals of Oncology 2007 18(12):2041; doi:10.1093/annonc/mdm499
© 2007 European Society for Medical Oncology
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Glycogen phosphorylase BB as a marker of cardiac toxicity during high-dose chemotherapy followed by hematopoietic cell transplantation
Cardiotoxicity is a potentially serious complication of oncology treatment. Myeloablative preparative regimen (PR) followed by hematopoietic cell transplantation (HCT) represents high risk for the development of cardiotoxicity [1]. Various methods have been recommended for monitoring cardiotoxicity in oncology. Recently, the applicability of cardiac troponins (cTnT, cTnI) has been investigated in this context and the results are inconsistent [2, 3]. Therefore, we evaluated the possible role of new perspective biomarkers of cardiac injury—heart fatty acid-binding protein (H-FABP) and glycogen phosphorylase BB (GPBB) [4, 5]. According to the available literature, there are no data on using these biomarkers in this context.The aim of our pilot study was to assess cardiotoxicity during PR and HCT with biomarkers of myocardial injury—myoglobin, creatine kinase MB (CK-MB) mass, cTnT (Roche), cTnI, H-FABP and GPBB (Randox).
Nineteen patients (mean age 42.8 ± 10.0 years, 13 males) pretreated with anthracycline-based chemotherapy for acute leukemia were studied. PR consisted of high-dose cyclophosphamide 120 mg/kg in combination with busulphan or total body irradiation, followed by HCT. All patients had normal liver and renal functions during the study. Biomarkers of cardiac injury were measured on Elecsys Roche and Evidence Randox analyzers the day before PR (baseline), the day after PR, the day after HCT and 14 days after HCT. Concentrations of cardiac biomarkers diagnostic for cardiotoxicity of oncology treatment have not been established yet. In our study, values above the reference range recommended by the manufacturer were considered elevated. The cut-off values were as follows: 76.0 µg/l for myoglobin, 4.80 µg/l for CK-MB mass, 0.01 µg/l for cTnT, 0.40 µg/l for cTnI, 4.50 µg/l for H-FABP and 7.30 µg/l for GPBB.
Before PR, all biomarkers were below the cut-off values in all patients. GPBB became elevated (>7.30 µg/l) in five (26.3%) patients the day after PR, remained elevated in five (26.3%) the day after HCT and in one (5.3%) 14 days after HCT. The changes in GPBB were significant in comparison with the baseline values (P < 0.01). Other biomarkers (myoglobin, CK-MB mass, cTnT, cTnI and H-FABP) remained within the reference range in all the patients.
Our results show that administration of PR containing high-dose cyclophosphamide followed by HCT may be associated with myocardial injury manifested by increased release of GPBB from cardiomyocytes in our cohort in five (26.3%) patients early after PR and HCT. These findings could be considered a sign of acute subclinical cardiotoxicity of this treatment. Whether these acute changes will predict treatment-related cardiomyopathy in the future is unclear and must be evaluated during a prospective follow-up. Persistent GPBB elevation in one (5.3%) patient 14 days after HCT could be a sign of subacute cardiac toxicity related to undergone oncology treatment (prior anthracycline-based chemotherapy and recent administration of PR). According to our results, other sensitive markers of myocardial injury (cTnT, cTnI, H-FABP, CK-MB mass and myoglobin) do not seem to be of value in the detection of cardiotoxicity during PR and HCT in acute leukemia. Further studies will be necessary to confirm our preliminary results and define the potential role of new biomarkers in this context.
funding
Czech Ministry of Defence (MO 0FVZ 0000503) and Czech Ministry of Health (MZO 00179906).
1 2nd Department of Medicine–Clinical Hematology
2 Institute of Clinical Biochemistry and Diagnostics
3 1st Department of Medicine, Faculty of Medicine and University Hospital, Sokolska 581, 50005 Hradec Kralove
4 Department of Internal Medicine, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 50001 Hradec Kralove, Czech Republic
* (E-mail: jan.hor{at}post.cz)
References
1. Morandi P, Ruffini PA, Benvenuto GM, et al. Cardiac toxicity of high-dose chemotherapy. Bone Marrow Transplant (2005) 35:323–334.[CrossRef][Web of Science][Medline]
2. Sparano JA, Brown DL, Wolff AC. Predicting cancer therapy-induced cardiotoxicity. The role of troponins and other markers. Drug Saf (2002) 25:301–311.[CrossRef][Web of Science][Medline]
3. Auner HW, Tinchon C, Brezinschek RI, et al. Monitoring of cardiac function by serum cardiac troponin T levels, ventricular repolarization indices, and echocardiography after conditioning with fractionated total body irradiation and high-dose cyclophosphamide. Eur J Haematol (2002) 69:1–6.[CrossRef][Web of Science][Medline]
4. Azzazy HM, Pelsers MM, Christenson RH. Unbound free fatty acids and heart-type fatty acid-binding protein: diagnostic assays and clinical applications. Clin Chem (2006) 52:19–29.
5. Peetz D, Post F, Schinzel H, Schweigert R, et al. Glycogen phosphorylase BB in acute coronary syndromes. Clin Chem Lab Med (2005) 43:1351–1358.[CrossRef][Web of Science][Medline]
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