The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia
Aim: Monitoring of cardiotoxicity of conventional and high-dose chemotherapy (HD-CT) with multiple biomarkers of cardiac injury — glycogen phosphorylase BB (GPBB), heart-type fatty acid binding protein (H-FABP), cardiac troponins (cTnT, cTnI), creatine kinase MB (CK-MB mass), myoglobin. Methods: A t...
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Horacek, J.M. Vasatova, M. Tichy, M. Pudil, R. Jebavy, L. Maly, J. 2018-06-19T10:22:56Z 2018-06-19T10:22:56Z 2010 The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia / J.M. Horacek, M. Vasatova, M. Tichy, R. Pudil, L. Jebavy, J. Maly // Experimental Oncology. — 2010. — Т. 32, № 2. — С. 97-99. — Бібліогр.: 26 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/138602 Aim: Monitoring of cardiotoxicity of conventional and high-dose chemotherapy (HD-CT) with multiple biomarkers of cardiac injury — glycogen phosphorylase BB (GPBB), heart-type fatty acid binding protein (H-FABP), cardiac troponins (cTnT, cTnI), creatine kinase MB (CK-MB mass), myoglobin. Methods: A total of 47 adult acute leukemia patients were studied — 24 patients treated with conventional CT containing anthracyclines (ANT) and 23 patients treated with HD-CT (myeloablative preparative regimen) followed by hematopoietic cell transplantation (HCT). Cardiac biomarkers were assessed prior to treatment (before CT/HD-CT), after first CT with ANT, after last CT with ANT in the first group, after HD-CT and after HCT in the second group. Values above the reference range were considered elevated. Results: Before CT/HD-CT, all biomarkers of cardiac injury were below the cut-offs in all patients. GPBB increased above the cut-off (7.30 μg/L) in 4 (16.7%) patients after first CT and in 5 (20.8%) patients after last CT with ANT. GPBB increased above the cut-off in 5 (21.7%) patients after HD-CT and remained elevated in 5 (21.7%) patients after HCT. CTnI became elevated (above 0.40 μg/L) in 2 (8.3%) patients after first and last CT with ANT. Both patients with cTnI positivity had elevated GPBB. Other tested biomarkers remained below the cut-offs during the study. Conclusion: Our results suggest that GPBB could become a sensitive biomarker for detection of acute cardiotoxicity associated with conventional CT containing ANT and HD-CT followed by HCT. The predictive value for development of cardiomyopathy in the future is not known and should be evaluated during a prospective follow-up. Based on our data, a larger prospective and multicenter study would be most desirable to define the potential role of new circulating biomarkers in the assessment of cardiotoxicity in oncology. The work was supported by research projects MO 0FVZ0000503 (Czech Ministry of Defence) and MZO 00179906 (Czech Ministry of Health) and MSM 0021620817 (Czech Ministry of Education). en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia Article published earlier |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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| title |
The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia |
| spellingShingle |
The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia Horacek, J.M. Vasatova, M. Tichy, M. Pudil, R. Jebavy, L. Maly, J. Original contributions |
| title_short |
The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia |
| title_full |
The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia |
| title_fullStr |
The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia |
| title_full_unstemmed |
The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia |
| title_sort |
use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia |
| author |
Horacek, J.M. Vasatova, M. Tichy, M. Pudil, R. Jebavy, L. Maly, J. |
| author_facet |
Horacek, J.M. Vasatova, M. Tichy, M. Pudil, R. Jebavy, L. Maly, J. |
| topic |
Original contributions |
| topic_facet |
Original contributions |
| publishDate |
2010 |
| language |
English |
| container_title |
Experimental Oncology |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| format |
Article |
| description |
Aim: Monitoring of cardiotoxicity of conventional and high-dose chemotherapy (HD-CT) with multiple biomarkers of cardiac injury — glycogen phosphorylase BB (GPBB), heart-type fatty acid binding protein (H-FABP), cardiac troponins (cTnT, cTnI), creatine kinase MB (CK-MB mass), myoglobin. Methods: A total of 47 adult acute leukemia patients were studied — 24 patients treated with conventional CT containing anthracyclines (ANT) and 23 patients treated with HD-CT (myeloablative preparative regimen) followed by hematopoietic cell transplantation (HCT). Cardiac biomarkers were assessed prior to treatment (before CT/HD-CT), after first CT with ANT, after last CT with ANT in the first group, after HD-CT and after HCT in the second group. Values above the reference range were considered elevated. Results: Before CT/HD-CT, all biomarkers of cardiac injury were below the cut-offs in all patients. GPBB increased above the cut-off (7.30 μg/L) in 4 (16.7%) patients after first CT and in 5 (20.8%) patients after last CT with ANT. GPBB increased above the cut-off in 5 (21.7%) patients after HD-CT and remained elevated in 5 (21.7%) patients after HCT. CTnI became elevated (above 0.40 μg/L) in 2 (8.3%) patients after first and last CT with ANT. Both patients with cTnI positivity had elevated GPBB. Other tested biomarkers remained below the cut-offs during the study. Conclusion: Our results suggest that GPBB could become a sensitive biomarker for detection of acute cardiotoxicity associated with conventional CT containing ANT and HD-CT followed by HCT. The predictive value for development of cardiomyopathy in the future is not known and should be evaluated during a prospective follow-up. Based on our data, a larger prospective and multicenter study would be most desirable to define the potential role of new circulating biomarkers in the assessment of cardiotoxicity in oncology.
|
| issn |
1812-9269 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/138602 |
| citation_txt |
The use of cardiac biomarkers in detection of cardiotoxicity associated with conventional and high-dose chemotherapy for acute leukemia / J.M. Horacek, M. Vasatova, M. Tichy, R. Pudil, L. Jebavy, J. Maly // Experimental Oncology. — 2010. — Т. 32, № 2. — С. 97-99. — Бібліогр.: 26 назв. — англ. |
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2025-11-27T09:28:54Z |
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| fulltext |
Experimental Oncology 32, 97–99, 2010 (June) 97
Cardiotoxicity is a well-known and potentially
serious complication of anticancer therapy that can
significantly impair patient’s quality of life and also
substantially increase health care costs. The greatest
risk for development of cardiotoxicity represent an-
thracyclines (ANT) [1–3] and high-dose chemotherapy
(HD-CT) especially regimens containing high-dose
cyclophosphamide [4–6]. Various methods have
been recommended for monitoring of cardiotoxicity
in oncology [7, 8]. In our conditions, echocardiogra-
phy and electrocardiography are routinely used [9,
10]. Recently, biochemical markers of cardiac injury,
especially cardiac troponins and natriuretic peptides,
have been investigated in the assessment of cancer
therapy-induced cardiotoxicity [11–13].
Cardiac troponins — cardiac troponin T (cTnT),
cardiac troponin I (cTnI) — and myocardial izoenzyme
of creatine kinase (CK-MB) are cardiospecific markers
that show structural injury of cardiomyocytes from va-
rious causes, including cardiotoxic effect of anticancer
therapy [14–17].
Heart-type fatty acid binding protein (H-FABP)
and glycogen phosphorylase isoenzyme BB (GPBB)
are new perspective markers of myocardial ischemia
and necrosis, recently evaluated in the diagnostics
and risk stratification of acute coronary syndromes
[18–22]. H-FABP is a relatively small cytoplasmic pro-
tein for the oxidation of fatty acids that is quite specific
for cardiac muscle. H-FABP is rapidly released from
the myocardium into the bloodstream after ischemic
injury. Plasma H-FABP increases above the reference
limit within 2–3 h of the onset of myocardial injury and
returns to normal within 18–30 h. GPBB is a glyco-
genolytic enzyme providing glucose for heart muscle
tissue. After glycogenolysis in ischemic tissue, GPBB
is released from the sarcoplasmic reticulum into the
cytoplasm and then into the circulation through the
damaged cell membrane. GPBB is released into the
circulation 2–4 h after myocardial injury, returning to
normal va lues within 24–36 h of damage occurring.
In the acute coronary syndrome setting, both markers
are regarded early markers of cardiac injury due to
acute myocardial ischemia. However, the main mecha-
nism of cardiac injury caused by anticancer therapy is
THE USE OF CARDIAC BIOMARKERS IN DETECTION
OF CARDIOTOXICITY ASSOCIATED WITH CONVENTIONAL
AND HIGH-DOSE CHEMOTHERAPY FOR ACUTE LEUKEMIA
J.M. Horacek1, 2, *, M. Vasatova3, M. Tichy3, R. Pudil4, L. Jebavy1, 2, J. Maly1
1Department of Medicine II — Clinical Hematology, University Hospital and Charles University,
Faculty of Medicine in Hradec Kralove, Czech Republic
2Department of Internal Medicine, University of Defence,
Faculty of Military Health Sciences in Hradec Kralove, Czech Republic
3Institute of Clinical Biochemistry and Diagnostics, University Hospital and Charles University,
Faculty of Medicine in Hradec Kralove, Czech Republic
4Department of Medicine I — Cardiology, University Hospital and Charles University,
Faculty of Medicine in Hradec Kralove, Czech Republic
Aim: Monitoring of cardiotoxicity of conventional and high-dose chemotherapy (HD-CT) with multiple biomarkers of cardiac
injury — glycogen phosphorylase BB (GPBB), heart-type fatty acid binding protein (H-FABP), cardiac troponins (cTnT, cTnI),
creatine kinase MB (CK-MB mass), myoglobin. Methods: A total of 47 adult acute leukemia patients were studied — 24 patients
treated with conventional CT containing anthracyclines (ANT) and 23 patients treated with HD-CT (myeloablative preparative
regimen) followed by hematopoietic cell transplantation (HCT). Cardiac biomarkers were assessed prior to treatment (before
CT/HD-CT), after first CT with ANT, after last CT with ANT in the first group, after HD-CT and after HCT in the second
group. Values above the reference range were considered elevated. Results: Before CT/HD-CT, all biomarkers of cardiac injury
were below the cut-offs in all patients. GPBB increased above the cut-off (7.30 μg/L) in 4 (16.7%) patients after first CT and in
5 (20.8%) patients after last CT with ANT. GPBB increased above the cut-off in 5 (21.7%) patients after HD-CT and remained
elevated in 5 (21.7%) patients after HCT. CTnI became elevated (above 0.40 μg/L) in 2 (8.3%) patients after first and last CT with
ANT. Both patients with cTnI positivity had elevated GPBB. Other tested biomarkers remained below the cut-offs during the study.
Conclusion: Our results suggest that GPBB could become a sensitive biomarker for detection of acute cardiotoxicity associated with
conventional CT containing ANT and HD-CT followed by HCT. The predictive value for development of cardiomyopathy in the future
is not known and should be evaluated during a prospective follow-up. Based on our data, a larger prospective and multicenter study
would be most desirable to define the potential role of new circulating biomarkers in the assessment of cardiotoxicity in oncology.
Key Words: cardiotoxicity, biomarkers, glycogen phosphorylase BB, chemotherapy, anthracyclines, high-dose.
Received: March 10, 2010.
*Correspondence: E-mail: jan.hor@post.cz
Abbreviations used: ALL — acute lymphoblastic leukemia; AML —
acute myeloid leukemia; ANT — anthracyclines; CK-MB — creatine
kinase MB; CT — chemotherapy; cTnI — cardiac troponin I; cTnT —
cardiac troponin T; GPBB — glycogen phosphorylase BB; HCT —
hematopoietic cell transplantation; HD-CT — high-dose chemo-
therapy; H-FABP — heart-type fatty acid binding protein.
Exp Oncol 2010
32, 2, 97–99
98 Experimental Oncology 32, 97–99, 2010 (June)
mainly non-ischemic and prior cyclic exposition to ANT
agents may play a role (chronic and late cardiotoxici-
ty). Therefore, it is difficult to estimate the kinetics of
release of these biomarkers from cardiomyocytes in
this setting. At present, new perspective biomarkers
of cardiotoxicity have been evaluated inadequately in
patients treated for oncological diseases.
The aim of our study was to evaluate cardiac toxi city
of conventional CT containing ANT and HD-CT followed
by hematopoietic cell transplantation (HCT) with mul-
tiple biomarkers of cardiac injury: glycogen phosphory-
lase BB (GPBB), heart-type fatty acid binding protein
(H-FABP), cardiac troponins (cTnT, cTnI), creatine kinase
MB (CK-MB mass), myoglobin. Experience with GPBB
and H-FABP in this context is very limited.
PATIENTS AND METHODS
A total of 47 patients treated for acute leukemia
were included in the study. The study population was
divided into 2 groups — (1) 24 patients treated with
conventional CT containing ANT (3–6 cycles of CT,
mean total cumulative ANT dose 463.2 ± 114.3 mg/m2),
mean age 48.1 ± 10.9 years, 13 males. All patients had
de novo acute myeloid leukemia (AML): 2 — AML M1,
16 — AML M2, 5 — AML M4, 1 — AML M5 according
to FAB classification; (2) 23 patients treated with HD-
CT (ablative preparative regimen containing high-dose
cyclophosphamide in the total dose of 120 mg/kg in
combination with peroral busulfan 16 mg/kg /BuCy2/
or fractionated total body irradiation 12 Gy /CyTBI/) fol-
lowed by HCT, mean age of 44.5 ± 10.6 years, 15 males.
Twenty patients had AML, from that 2 — AML M1, 14 —
AML M2, 4 — AML M4 according to FAB classification,
and 3 patients had acute lymphoblastic leukemia (ALL),
from that 2 — B-ALL, 1 — T-ALL. All patients had normal
liver and renal functions during the study. The study was
carried out with approval from the ethics committee.
All patients gave a written consent before they were
included in the study.
In the first group, biochemical analysis was per-
formed at the baseline (before CT), the day after first
CT with ANT (after first CT; mean cumulative ANT dose
130.6 ± 29.8 mg/m2), the day after last CT with ANT (af-
ter last CT; mean cumulative dose 463.2 ± 114.3 mg/m2).
In the second group, cardiac biomarkers were assessed
the day before administration of HD-CT (before HD-CT),
the day after completion of HD-CT (after HD-CT) and
the day after HCT (after HCT).
Circulating biomarkers of cardiac injury were
measured according to the manufacturer’s guidelines
as follows: cTnT, CK-MB mass, myoglobin (Roche
Diagnostics; Elecsys analyzer), GPBB, H-FABP, cTnI
(Randox; Evidence Investigator analyzer).
Concentrations of cardiac biomarkers diagnostic
for cardiotoxicity of oncology treatment have not been
established yet. On that ground, values above the refe-
rence range based on a number of cardiology studies
and recommended by the manufacturers were consi-
dered 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.
RESULTS
The cut-off values of all biomarkers and the number of
patients with elevated values are shown in Table 1 and 2.
Table 1. Elevated biomarkers of cardiac injury in association with
anthracycline-based chemotherapy (n = 24)
Cardiac biomarkers Before CT After first CT After last CT
Myoglobin above 76.0 μg/L 0 0 0
CK-MB mass above 4.80 μg/L 0 0 0
cTnT above 0.01 μg/L 0 0 0
cTnI above 0.40 μg/L 0 2 (8.3%) 2 (8.3%)
H-FABP above 4.50 μg/L 0 0 0
GPBB above 7.30 μg/L 0 4 (16.7%) 5 (20.8%)
In Table 1 and 2: CT — chemotherapy; HD-CT — high-dose chemotherapy;
HCT — hematopoietic cell transplantation; CK-MB mass — creatine kinase
MB; cTnT — cardiac troponin T; cTnI — cardiac troponin I; H-FABP — heart-
type fatty acid binding protein; GPBB — glycogen phosphorylase BB.
Table 2. Elevated biomarkers of cardiac injury in association with high-
dose chemotherapy and hematopoietic cell transplantation (n = 23)
Cardiac biomarkers Before HD-CT After HD-CT After HCT
Myoglobin above 76.0 μg/L 0 0 0
CK-MB mass above 4.80 μg/L 0 0 0
cTnT above 0.01 μg/L 0 0 0
cTnI above 0.40 μg/L 0 0 0
H-FABP above 4.50 μg/L 0 0 0
GPBB above 7.30 μg/L 0 5 (21.7%) 5 (21.7%)
Before CT/HD-CT, all biomarkers of cardiac injury
were below the cut-off values in all patients. GPBB con-
centrations increased above the cut-off in 4 (16.7%)
patients after first CT and in 5 (20.8%) patients after
last CT with ANT. In the second group, GPBB increased
above the cut-off in 5 (21.7%) patients after HD-CT and
remained elevated in 5 (21.7%) patients after HCT. CTnI
concentrations became elevated in 2 (8.3%) patients
after first and last CT with ANT. Both patients with cTnI
positivity had elevated GPBB. CTnI remained nega-
tive after HD-CT and HCT in all patients. Other tested
biomarkers (H-FABP, cTnT, CK-MB mass, myoglobin)
remained below the cut-offs during conventional CT
containing ANT and HD-CT followed by HCT.
DISCUSSION
GPBB and H-FABP have been recently investi-
gated in the early detection of cardiac injury. They
have been suggested sensitive markers of myocardial
ischemia and necrosis in patients with acute coronary
synd romes [18–22]. Moreover, GPBB could be as-
sociated with pulmonary artery wedge pressure and
left ventricle mass index in patients with hypertrophic
cardiomyopathy. This finding raises an important is-
sue concerning the role of cardiac biomarkers in the
diagnosis of hypertrophic cardiomyopathy and could
potentially provide a useful tool to stratify these
patients [23]. However, in the field of cardiotoxicity
of anticancer therapy, these perspective biomarkers
of cardiac injury have been evaluated inadequately.
In 2008, we published our pilot study on usability
of multiple biomarkers, including GPBB and H-FABP,
for evaluation of ANT-induced cardiotoxicity in patients
with acute myeloid leukemia [24]. Recently, we applied
multiple biomarkers, including GPBB and H-FABP,
in the assessment of cardiotoxicity associated with
administration of preparative regimen and HCT for
Experimental Oncology 32, 97–99, 2010 (June) 99
various hematological malignancies [25]. ElGhan-
dour et al. [26] studied H-FABP in 40 non-Hodgkin’s
lymphoma patients treated with 6 cycles of CT contain-
ing doxorubicin (cumulative dose 300 mg/m2). The
authors concluded that H-FABP may serve as a reliable
early marker for prediction of cardiomyopathy induced
by doxorubicin. Otherwise, no studies have been
published so far and experience with these perspec-
tive biomarkers in the assessment of cardiotoxicity
of anticancer therapy is very limited.
In our present study on 47 acute leukemia patients,
we found significant elevations in GPBB after CT with
ANT (in 16.7% and 20.8% patients, respectively) and
after HD-CT followed by HCT (in 21.7% patients). In-
creased release of GPBB from cardiomyocytes after
administration of CT could be considered a sign of acute
subclinical cardiotoxicity of this treatment. Positivity of
GPBB in patients with negativity of other biomarkers
(cTnI, cTnT, H-FABP, CK-MB mass, myoglobin) sug-
gests that GPBB could be a more sensitive marker for
detection of acute cardiac injury caused by anticancer
therapy, both conventional and HD-CT. Whether these
acute changes will have predictive value for develop-
ment of CT-associated cardiomyopathy in the future is
not clear and should be evaluated during a prospective
follow-up. Based on our data, a larger prospective and
multicenter study would be most desirable to define
the potential role of new circulating biomarkers in the
assessment of cardiotoxicity in oncology.
ACKNOWLEDGMENTS
The work was supported by research projects
MO 0FVZ0000503 (Czech Ministry of Defence) and
MZO 00179906 (Czech Ministry of Health) and MSM
0021620817 (Czech Ministry of Education).
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