Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia
To assess cardiac toxicity of anthracycline treatment with six biomarkers of cardiac injury: myoglobin, creatine kinase MB (CK-MB mass), cardiac troponin T (cTnT), cardiac troponin I (cTnI), heart-type fatty acid binding protein (H-FABP), glycogen phosphorylase BB (GPBB). Methods: We evaluated anthr...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2008
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nasplib_isofts_kiev_ua-123456789-1391902025-02-09T14:53:56Z Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia Биомаркеры для оценки кардиотоксичности, вызванной антрациклином, у больных острой миелоидной лейкемией Horacek, J.M. Tichy, M. Jebavy, L. Pudil, R. Ulrychova, M. Maly, J. Uncategorized To assess cardiac toxicity of anthracycline treatment with six biomarkers of cardiac injury: myoglobin, creatine kinase MB (CK-MB mass), cardiac troponin T (cTnT), cardiac troponin I (cTnI), heart-type fatty acid binding protein (H-FABP), glycogen phosphorylase BB (GPBB). Methods: We evaluated anthracycline-induced cardiotoxicity in 12 acute myeloid leukemia patients (mean age 51.3 ± 10.7 years, 7 females). All biomarkers were measured at the baseline, after first chemotherapy (CT) with anthracyclines, after last CT with anthracyclines (total cumulative dose 479.8 ± 106.2 mg/m2) and 6 months thereafter. Values above the reference range were considered elevated. Results: GPBB increased above the cut-off (7.30 µg/L) in 2 (16.7%) patients after first CT, in 3 (25.0%) patients after last CT and remained elevated in 2 (16.7%) patients within 6 months after CT. CTnI became elevated (above 0.40 µg/L) in 1 (8.3%) patient after first and last CT and within 6 months after CT. CTnT remained negative (below 0.01 µg/L) during CT in all patients. Six months after CT, delayed cTnT positivity was found in 1 (8.3%) patient. All patients with cTnI or cTnT positivity had elevated GPBB. Other biomarkers (myoglobin, CK-MB mass, H-FABP) remained within the reference range in all patients. Conclusion: Our preliminary results suggest that GPBB could be a new promising marker for detection of anthracycline-related cardiotoxicity and probably superior to cardiac troponins. The predictive value for development of cardiomyopathy in the future is not clear and will be evaluated during a prospective follow-up. Цель: провести оценку кардиотоксичности, вызываемой антрациклином, с помощью ряда биомаркеров поражения сердца: миоглобина, креатин-киназы MB (CK-MB mass), кардиального тропонина T (cTnT), кардиального тропонина I (cTnI), белка, связывающего жирные кислоты (H-FABP), и гликогенфосфорилазы BB (GPBB). Методы: оценку кардиотоксичности проводили у 12 больных острой миелоидной лейкемией (средний возраст — 51,3 ± 10,7 года, 7 женщин). Измерены начальные показатели всех биомаркеров, а также таковые после проведения первой и последней химиотерапии (ХT) антрациклинами (общая накопленная доза — 479,8 ± 106,2 мг/м2 ) и через 6 мес после завершения терапии. Значения выше начальных рассматривали как повышенные. Результаты: уровень GPBB превысил норму (7,30 µg/L) у 2 больных (16,7%) после первой ХT, у 3 (25,0%) — после последней ХT и оставался повышенным у 2 больных (16,7%) и через 6 мес после ХT. Уровень CTnI повысился (более 0,40 µg/L) у 1 больного (8,3%) после первой и последней ХT, а также и через 6 мес после ХT. Значения CTnT оставались в пределах нормы (ниже 0,01 µg/L) во время проведения CT у всех пациентов. Через 6 мес после ХT отдаленная положительная реакция на cTnT выявлена у 1 больного (8,3%). У всех пациентов с положительными cTnI или cTnT установлен повышенный уровень GPBB. Другие биомаркеры (миоглобин, CK-MB, H-FABP) оставались в пределах нормы у всех больных. Выводы: предварительные результаты, полученные в данном исследовании, позволяют предположить, что GPBB можно рассматривать как новый перспективный маркер для выявления кардиотоксичности, вызванной антрациклинами, и, возможно, превосходит предложенные ранее тропонины. Возможная прогностическая ценность этого маркера при развитии кардиомиопатии пока не установлена. The study was supported by research projects MO 0FVZ 0000503 (Czech Ministry of Defence), MZO 00179906 (Czech Ministry of Health) and MSM 0021620817 (Czech Ministry of Education). 2008 Article Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia / J.M. Horacek, M. Tichy, L. Jebavy, R. Pudil, M. Ulrychova, J. Maly // Experimental Oncology. — 2008. — Т. 30, № 2. — С. 157–159. — Бібліогр.: 10 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/139190 en Experimental Oncology application/pdf Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Uncategorized Uncategorized Horacek, J.M. Tichy, M. Jebavy, L. Pudil, R. Ulrychova, M. Maly, J. Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia Experimental Oncology |
| description |
To assess cardiac toxicity of anthracycline treatment with six biomarkers of cardiac injury: myoglobin, creatine kinase MB (CK-MB mass), cardiac troponin T (cTnT), cardiac troponin I (cTnI), heart-type fatty acid binding protein (H-FABP), glycogen phosphorylase BB (GPBB). Methods: We evaluated anthracycline-induced cardiotoxicity in 12 acute myeloid leukemia patients (mean age 51.3 ± 10.7 years, 7 females). All biomarkers were measured at the baseline, after first chemotherapy (CT) with anthracyclines, after last CT with anthracyclines (total cumulative dose 479.8 ± 106.2 mg/m2) and 6 months thereafter. Values above the reference range were considered elevated. Results: GPBB increased above the cut-off (7.30 µg/L) in 2 (16.7%) patients after first CT, in 3 (25.0%) patients after last CT and remained elevated in 2 (16.7%) patients within 6 months after CT. CTnI became elevated (above 0.40 µg/L) in 1 (8.3%) patient after first and last CT and within 6 months after CT. CTnT remained negative (below 0.01 µg/L) during CT in all patients. Six months after CT, delayed cTnT positivity was found in 1 (8.3%) patient. All patients with cTnI or cTnT positivity had elevated GPBB. Other biomarkers (myoglobin, CK-MB mass, H-FABP) remained within the reference range in all patients. Conclusion: Our preliminary results suggest that GPBB could be a new promising marker for detection of anthracycline-related cardiotoxicity and probably superior to cardiac troponins. The predictive value for development of cardiomyopathy in the future is not clear and will be evaluated during a prospective follow-up. |
| format |
Article |
| author |
Horacek, J.M. Tichy, M. Jebavy, L. Pudil, R. Ulrychova, M. Maly, J. |
| author_facet |
Horacek, J.M. Tichy, M. Jebavy, L. Pudil, R. Ulrychova, M. Maly, J. |
| author_sort |
Horacek, J.M. |
| title |
Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia |
| title_short |
Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia |
| title_full |
Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia |
| title_fullStr |
Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia |
| title_full_unstemmed |
Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia |
| title_sort |
use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2008 |
| topic_facet |
Uncategorized |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/139190 |
| citation_txt |
Use of multiple biomarkers for evaluation of anthracycline-induced cardiotoxicity in patients with acute myeloid leukemia / J.M. Horacek, M. Tichy, L. Jebavy, R. Pudil, M. Ulrychova, J. Maly // Experimental Oncology. — 2008. — Т. 30, № 2. — С. 157–159. — Бібліогр.: 10 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
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2025-11-27T01:36:43Z |
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2025-11-27T01:36:43Z |
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| fulltext |
Experimental Oncology ��� �������� ���� ���ne� ������ �������� ���� ���ne� �����ne� ���� ��� ���
Cardiotoxicity is a potentially serio�s complication
of oncology treatment. Anthracyclines represent the
greatest risk for development of cardiotoxicity [�].
Vario�s methods have been recommended for moni-
toring of cardiotoxicity in oncology [�� �]. Recently�
the applicability of cardiac troponins �cTnT� cTnI� and
creatine kinase MB �CK-MB mass� has been investi-
gated in this setting and the res�lts of clinical st�dies
are inconsistent [4]. In several st�dies� no early ele-
vations of cardiac troponins and CK-MB mass after
administration of anthracyclines were fo�nd [���]. We
therefore eval�ated the possible role of new perspec-
tive biomarkers of myocardial ischemia and necro-
sis — heart-type fatty acid binding protein �H-FABP�
and glycogen phosphorylase BB �GPBB�� recently
investigated in the diagnostics and risk stratification of
ac�te coronary syndromes [����]. H-FABP is a rela-
tively small cytoplasmic protein for oxidation of fatty
acids that is q�ite specific for heart m�scle. Plasma
H-FABP increases above the reference range within
��� h of the onset of myocardial inj�ry and ret�rns
to normal within ����� h. GPBB is a glycogenolytic
enzyme providing gl�cose for the myocardi�m. Af-
ter glycogenolysis in the ischemic tiss�e� GPBB is
released from the sarcoplasmic retic�l�m into the
cytoplasm and then into the circ�lation thro�gh the
damaged cell membrane. GPBB is released into the
circ�lation ��4 h after myocardial inj�ry� ret�rning to
normal within �4��6 h of damage occ�rring. In the
ac�te coronary syndrome setting� both markers are
regarded early markers of cardiac inj�ry d�e to ac�te
myocardial ischemia. The main mechanism of cardiac
inj�ry ca�sed by anticancer therapy is mainly non-
ischemic and prior cyclic exposition to anthracycline
agents may play a role �chronic and late cardiotoxicity�.
Th�s� it is diffic�lt to estimate the kinetics of release
of these biomarkers from cardiomyocytes in this set-
ting. According to the available literat�re� there are no
data on �sability of these biomarkers for detection of
anthracycline-related cardiotoxicity.
The aim of o�r pilot st�dy was to assess cardiac
toxicity of anthracycline treatment with six biomar-
kers of cardiac inj�ry: myoglobin� CK-MB mass� cTnT
�Roche Diagnostics�� cTnI� H-FABP� GPBB �Randox
Laboratories Ltd.�.
Twelve patients �mean age ��.� ± ��.� years� � fe-
males� with de novo ac�te myeloid le�kemia �� — AML
M�� � — AML M4� � — AML M�� were st�died. The
patients were treated with ��6 cycles of conventional
use of MuLTIPLe BIoMARKeRs foR eVALuATIoN
of ANTHRACYCLINe-INDuCeD CARDIoToXICITY IN PATIeNTs
wITH ACuTe MYeLoID LeuKeMIA
J.M. Horacek1, 4, M. Tichy2, 4, L. Jebavy1, 4, R. Pudil3, M. Ulrychova2, J. Maly1
12nd Department of Medicine — Clinical Hematology, University Hospital and Charles University,
Faculty of Medicine in Hradec Kralove, Czech Republic
2 Institute of Clinical Biochemistry and Diagnostics, University Hospital and Charles University,
Faculty of Medicine in Hradec Kralove, Czech Republic
3 1st Department of Medicine, University Hospital and Charles University,
Faculty of Medicine in Hradec Kralove, Czech Republic
4 Department of Internal Medicine, University of Defence,
Faculty of Military Health Sciences in Hradec Kralove, Czech Republic
Aim: To assess cardiac toxicity of anthracycline treatment with six biomarkers of cardiac injury: myoglobin, creatine kinase MB
(CK-MB mass), cardiac troponin T (cTnT), cardiac troponin I (cTnI), heart-type fatty acid binding protein (H-FABP), glycogen
phosphorylase BB (GPBB). Methods: We evaluated anthracycline-induced cardiotoxicity in 12 acute myeloid leukemia patients
(mean age 51.3 ± 10.7 years, 7 females). All biomarkers were measured at the baseline, after first chemotherapy (CT) with an-
thracyclines, after last CT with anthracyclines (total cumulative dose 479.8 ± 106.2 mg/m2) and 6 months thereafter. Values above
the reference range were considered elevated. Results: GPBB increased above the cut-off (7.30 µg/L) in 2 (16.7%) patients after
first CT, in 3 (25.0%) patients after last CT and remained elevated in 2 (16.7%) patients within 6 months after CT. CTnI became
elevated (above 0.40 µg/L) in 1 (8.3%) patient after first and last CT and within 6 months after CT. CTnT remained negative
(below 0.01 µg/L) during CT in all patients. Six months after CT, delayed cTnT positivity was found in 1 (8.3%) patient. All pa-
tients with cTnI or cTnT positivity had elevated GPBB. Other biomarkers (myoglobin, CK-MB mass, H-FABP) remained within
the reference range in all patients. Conclusion: Our preliminary results suggest that GPBB could be a new promising marker for
detection of anthracycline-related cardiotoxicity and probably superior to cardiac troponins. The predictive value for development
of cardiomyopathy in the future is not clear and will be evaluated during a prospective follow-up.
Key Words: cardiac biomarkers, glycogen phosphorylase BB, cardiotoxicity, anthracyclines, chemotherapy, acute myeloid leukemia.
Received: March 16, 2008.
*Correspondence: E-mail: jan.hor@post.cz
Abbreviations used: CK-MB mass – creatine kinase MB;
CT – chemotherapy; cTnI – cardiac troponin I; cTnT – cardiac
troponin T; GPBB – glycogen phosphorylase BB; H-FABP – heart-
type fatty acid binding protein.
Exp Oncol ����
��� �� �������
��� Experimental Oncology ��� �������� ���� ���ne�
chemotherapy �CT� containing anthracycline agent
�idar�bicin� da�nor�bicin or mitoxantrone� in com-
bination with cytarabine �so called “� + �” or “� + �”
regimen� i. e. anthracycline agent for � or � days and
cytarabine for � or � days per a cycle�. The stan-
dard doses of anthracyclines for a cycle of CT were
as follows: idar�bicin � x �� mg/m�� da�nor�bicin
� x �� mg/m�� mitoxantrone ��� x �� mg/m�. To calc�-
late the c�m�lative dose of anthracyclines� we applied
conversion factors derived from the maxim�m recom-
mended c�m�lative doses for individ�al agents �sed.
The total c�m�lative dose of anthracyclines in o�r
cohort reached 4��.� ± ��6.� mg/m�. Three patients
were treated for arterial hypertension� other patients
had no history of cardiovasc�lar disease. All patients
had normal liver and renal f�nctions d�ring the st�dy.
Biomarkers of cardiac inj�ry were meas�red on Elecsys
Roche and Evidence Randox analyzers at the baseline
�before CT�� the day after first CT with anthracyclines
�after first CT� c�m�lative dose ��4.� ± ��.� mg/m���
the day after last CT with anthracyclines �after last
CT� total c�m�lative dose 4��.� ± ��6.� mg/m�� and
6 months after completion of treatment �6 months
after CT�. Concentrations of cardiac biomarkers di-
agnostic for cardiotoxicity of anticancer therapy have
not been established yet. In o�r st�dy� val�es above
the reference range based on a n�mber of st�dies and
recommended by the man�fact�rer were considered
elevated. The c�t-off val�es for individ�al biomarkers
were as follows: �6.� µg/L for myoglobin� 4.�� µg/L for
CK-MB mass� �.�� µg/L for cTnT� �.4� µg/L for cTnI�
4.�� µg/L for H-FABP� �.�� µg/L for GPBB.
The res�lts are shown in the Table. Before CT� all
biomarkers of cardiac inj�ry were below the c�t-off
val�es in all patients. GPBB concentrations increased
above the c�t-off ��.�� µg/L� in � patients after first
CT� in � patients after last CT and remained elevated
in � patients within 6 months after CT. CTnI became
elevated �above �.4� µg/L� in � patient after first CT
and last CT and remained elevated within 6 months
after CT. CTnT concentrations were negative �below
�.�� µg/L� after first and last CT in all patients. Six
months after completion of CT� we fo�nd delayed cTnT
positivity in � patient. All patients with positivity of cTnI
or cTnT had elevated GPBB as well. Other biomarkers
�myoglobin� CK-MB mass� H-FABP� remained within
the reference range in all patients.
Table. Elevated biomarkers of cardiac injury in acute myeloid leukemia
patients treated with anthracyclines (n = 12)
Cardiac biomarkers Before
CT
After first
CT
After last
CT
6 months
after CT
Myoglobin above 76.0 µg/L 0 0 0 0
CK-MB mass above 4.80 µg/L 0 0 0 0
cTnT above 0.01 µg/L 0 0 0 1 (8.3%)
cTnI above 0.40 µg/L 0 1 (8.3%) 1 (8.3%) 1 (8.3%)
H-FABP above 4.50 µg/L 0 0 0 0
GPBB above 7.30 µg/L 0 2 (16.7%) 3 (25.0%) 2 (16.7%)
Notes: CT – chemotherapy; 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.
O�r res�lts s�ggest that anthracycline treatment
in ac�te myeloid le�kemia may be associated with
myocardial inj�ry manifested by increased release of
GPBB from cardiomyocytes� in o�r cohort in � ��6.�%�
patients after first CT with anthracyclines and in
� ���.�%� patients after last CT with anthracyclines�
respectively. These findings co�ld be considered a
sign of ac�te s�bclinical cardiotoxicity of anthracycline
treatment. Persistent GPBB elevations in � ��6.�%� pa-
tients within 6 months after completion of CT co�ld be
a sign of chronic cardiac toxicity related to �ndergone
oncology treatment. Whether these changes will have
predictive val�e for treatment-related cardiomyopathy
in the f�t�re is not clear and m�st be eval�ated d�r-
ing a prospective follow-�p. According to o�r res�lts�
GPBB seems to be a promising marker for eval�ation
of anthracycline-ind�ced cardiotoxicity and probably
s�perior to cardiac troponins �cTnI� cTnT� in this setting.
Other biomarkers of cardiac inj�ry �H-FABP� CK-MB
mass� myoglobin� do not seem to be of val�e in the
detection of cardiotoxicity d�ring anthracycline treat-
ment in ac�te myeloid le�kemia. F�rther st�dies in a
larger n�mber of patients will be necessary to confirm
o�r preliminary res�lts and define the potential role of
new biomarkers in the eval�ation of treatment-related
cardiotoxicity in oncology.
ACKNowLeDGeMeNTs
The st�dy was s�pported by research projects
MO �FVZ ������� �Czech Ministry of Defence��
MZO �������6 �Czech Ministry of Health� and MSM
����6����� �Czech Ministry of Ed�cation�.
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Experimental Oncology ��� �������� ���� ���ne� ������ �������� ���� ���ne� �����ne� ���� ��� ���
БИОМАРКЕРы ДЛЯ ОЦЕНКИ КАРДИОТОКСИЧНОСТИ,
ВыЗВАННОЙ АНТРАЦИКЛИНОМ, у БОЛьНых ОСТРОЙ
МИЕЛОИДНОЙ ЛЕЙКЕМИЕЙ
Цель: провести оценку кардиотоксичности, вызываемой антрациклином, с помощью ряда биомаркеров поражения сердца:
миоглобина, креатин-киназы MB (CK-MB mass), кардиального тропонина T (cTnT), кардиального тропонина I (cTnI),
белка, связывающего жирные кислоты (H-FABP), и гликогенфосфорилазы BB (GPBB). Методы: оценку кардиотоксич-
ности проводили у 12 больных острой миелоидной лейкемией (средний возраст — 51,3 ± 10,7 года, 7 женщин). Измерены
начальные показатели всех биомаркеров, а также таковые после проведения первой и последней химиотерапии (ХT) ан-T) ан-) ан-
трациклинами (общая накопленная доза — 479,8 ± 106,2 мг/м2) и через 6 мес после завершения терапии. Значения выше
начальных рассматривали как повышенные. Результаты: уровень GPBB превысил норму (7,30 µg/L) у 2 больных (16,7%)
после первой ХT, у 3 (25,0%) — после последней ХT и оставался повышенным у 2 больных (16,7%) и через 6 мес после ХT.
Уровень CTnI повысился (более 0,40 µg/L) у 1 больного (8,3%) после первой и последней ХT, а также и через 6 мес после
ХT. Значения CTnT оставались в пределах нормы (ниже 0,01 µg/L) во время проведения CT у всех пациентов. Через 6 мес
после ХT отдаленная положительная реакция на cTnT выявлена у 1 больного (8,3%). У всех пациентов с положительными
cTnI или cTnT установлен повышенный уровень GPBB. Другие биомаркеры (миоглобин, CK-MB, H-FABP) оставались в
пределах нормы у всех больных. Выводы: предварительные результаты, полученные в данном исследовании, позволяют
предположить, что GPBB можно рассматривать как новый перспективный маркер для выявления кардиотоксичности,
вызванной антрациклинами, и, возможно, превосходит предложенные ранее тропонины. Возможная прогностическая
ценность этого маркера при развитии кардиомиопатии пока не установлена.
Ключевые слова: кардиальные биомаркеры, гликоген фосфорилаза BB, кардиотоксичность, антрациклины, химиотерапия,
острая миелоидная лейкемия.
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