natriuretic-peptide--brain and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Doxorubicin causes cardiac injury and cardiomyopathy in children with acute lymphoblastic leukemia (ALL). Measuring biomarkers during therapy might help individualize treatment by immediately identifying cardiac injury and cardiomyopathy.. Children with high-risk ALL were randomly assigned to receive doxorubicin alone (n = 100; 75 analyzed) or doxorubicin with dexrazoxane (n = 105; 81 analyzed). Echocardiograms and serial serum measurements of cardiac troponin T (cTnT; cardiac injury biomarker), N-terminal pro-brain natriuretic peptide (NT-proBNP; cardiomyopathy biomarker), and high-sensitivity C-reactive protein (hsCRP; inflammatory biomarker) were obtained before, during, and after treatment.. cTnT levels were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before treatment but in 47% and 13%, respectively, after treatment (P = .005). NT-proBNP levels were increased in 89% of children in the doxorubicin group and in 92% of children in the doxorubicin-dexrazoxane group before treatment but in only 48% and 20%, respectively, after treatment (P = .07). The percentage of children with increased hsCRP levels did not differ between groups at any time. In the first 90 days of treatment, detectable increases in cTnT were associated with abnormally reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness 4 years later (P < .01); increases in NT-proBNP were related to an abnormal LV thickness-to-dimension ratio, suggesting LV remodeling, 4 years later (P = .01). Increases in hsCRP were not associated with any echocardiographic variables.. cTnT and NT-proBNP may hold promise as biomarkers of cardiotoxicity in children with high-risk ALL. Definitive validation studies are required to fully establish their range of clinical utility.

Topics: Antibiotics, Antineoplastic; Biomarkers; C-Reactive Protein; Cardiomyopathies; Cardiotonic Agents; Child; Child, Preschool; Doxorubicin; Echocardiography; Female; Heart; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Razoxane; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Troponin T; Ventricular Function, Left; Ventricular Remodeling

Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes and often induced by chemotherapy. Recombinant human interleukin-11 (rhIL-11) is a cytokine that can stimulate thrombopoiesis and is commonly used to treat thrombocytopenia. We observed the side effects of rhIL-11 in 24 leukemia patients with chemotherapy-induced thrombocytopenia. To determine the cardiovascular effects of rhIL-11, we detected changes in the patients' serum brain natriuretic peptide (BNP), blood pressure fluctuations, weight change, and whether edema or heart failure occurred in leukemia patients after chemotherapy. The results showed that BNP was significantly elevated after using rhIL-11 (P < 0. 05) but regressed after 2-4 days. Furthermore, nine patients had edema and experienced weight gain, and four experienced acute left heart failure. In addition, the average blood pressure was 119/75 mmHg (range 139/86 mmHg to 99/64 mmHg) before rhIL-11 administration and 127/79 mmHg (range 146/89 mmHg to 108/69 mmHg) after rhIL-11 use. In conclusion, although rhIL-11 is useful for treating chemotherapy-induced thrombocytopenia, it is important to monitor the patients' clinical status and re-examine BNP levels frequently during the use of rhIL-11. Furthermore, senile patients should be given special attention. However, the appropriate timing to begin and discontinue rhIL-11 treatment needs further investigation.

Topics: Adult; Aged; Animals; Humans; Interleukin-11; Male; Middle Aged; Natriuretic Peptide, Brain; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rats; Thrombocytopenia

To describe the high-risk profile group, susceptible to develop anthracycline-induced cardiomyopathy in children with acute leukemia.. The study involved 35 pediatric patients diagnosed with acute lymphoblastic (ALL) or acute myeloblastic leukemia (AML), from March 2014 to December 2016. Serologic markers used for the analysis of cardiac dysfunction were troponin T, NT-proBNP and PCRhs. Also, the patients have had echocardiographic evaluation at the beginning of treatment to determine LVEF, SF and A, E, E' Doppler waves.. Positive linear correlation was shown between NT-proBNP and leukocyte values, NT-proBNP and blast cells value, and NT-proBNP and LDH. Significant linear negative correlations between LVEF with leukocyte values, blast cells values, LDH, SF and leukocyte values, LVEF and NT-proBNP values and LVEF and troponin T values were also identified. A weak negative correlation between E/E' ratio and blast cells values has been observed. All of these correlations were statistically significant (p<0.05).. Leukocyte value, as well as the other serological markers assessed (NT-proBNP, Troponin T), are useful tools to evaluate the risk of anthracycline-induced cardiotoxicity. The variation of the biological markers at the beginning of the cytotoxic treatment confirms the presence of an early myocardial dysfunction, emphasizing the importance of systematic evaluation of this particular group of patients.

Topics: Adolescent; Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Cardiotoxicity; Child; Child, Preschool; Echocardiography; Female; Follow-Up Studies; Humans; Infant; Leukemia, Myeloid, Acute; Male; Natriuretic Peptide, Brain; Peptide Fragments; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Risk Assessment; Survival Rate; Troponin T

Despite significant improvements in the prognosis of childhood acute lymphoblastic leukaemia (ALL), the risk of anthracycline-induced cardiovascular disease remains a major concern. This study was designed to investigate the role of the myocardial performance index (MPI) and serum concentrations of biomarkers (cTnT and NT-pro-BNP) in the early detection of subclinical anthracycline-induced functional alterations in children with ALL.. All children consecutively admitted to our Pediatric Oncologic Department from January 2009 to October 2010 with a diagnosis of ALL were enrolled in this study. cTnT and NT-pro-BNP were evaluated in all patients at diagnosis, before doxorubicin therapy and 2 and 24 h following each anthracycline administration. ECG and echocardiography were performed at diagnosis and 24 h after each anthracycline course.. Nineteen children with standard-risk ALL were evaluated. The mean age was 6 years. The cumulative doxorubicin dosage was 240 mg/m(2) according to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) ALL 2000 protocol. None of the 19 patients developed congestive heart failure. With increasing cumulative dosages of anthracyclines a significant increase was observed in MPI. This increase was statistically significant starting from the cumulative dosage of 120 mg/m(2) compared to baseline, while the median NT-pro-BNP level did not change significantly during treatment and cTnT levels never exceeded the cut-off value for cardiac injury.. MPI value is a sensitive and accurate parameter, allowing subclinical cardiac dysfunction to be detected in children receiving anthracyclines. Lifelong cardiac surveillance of these patients is warranted in order to determine the clinical implications of increased MPI on long-term cardiac status.

Topics: Cardiotoxins; Child; Child, Preschool; Doxorubicin; Early Diagnosis; Echocardiography; Female; Heart; Heart Failure; Humans; Infant; Male; Natriuretic Peptide, Brain; Peptide Fragments; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Troponin C

The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines.. Cardiac function of 60 children with ALL was prospectively studied with measurements of cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and conventional and myocardial 2D strain echocardiography before start (T = 0), after 3 months (T = 1), and after 1 year (T = 2), and were compared with 60 healthy age-matched controls. None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening. Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls. Cardiac troponin T levels were abnormal in 11% of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 (P = 0.003). N-terminal-pro-brain natriuretic peptide levels were abnormal in 13% of patients at T = 1 and in 20% at T = 2, absolute values increased throughout treatment in 59%. Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1, for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline.. Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography. N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore, the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines.

Topics: Adolescent; Anthracyclines; Biomarkers; Case-Control Studies; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography; Female; Follow-Up Studies; Heart Function Tests; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Risk Assessment; Stroke Volume; Survival Rate; Treatment Outcome; Troponin T; Ventricular Dysfunction, Left

Exposure to anthracyclines (ANT) during childhood represents a high risk for development of late cardiotoxicity. Cardiotoxicity is usually detected only when clinical symptoms or progressive cardiac dysfunction have already occurred. Early detection of cardiotoxicity may lead to better therapeutic outcome. N-terminal pro-brain natriuretic peptide (NTproBNP) has been hypothesized to reflect increased left ventricular wall stress before development of echocardiographic abnormalities. The aim of this study was to detect cardiac abnormalities using plasma NTproBNP and echocardiography in asymptomatic childhood leukemia survivors treated with or without cardiotoxic anthracycline therapy.. Serum levels of NTproBNP were determined in 69 asymptomatic survivors of childhood leukemia treated with or without anthracyclines and in 44 apparently healthy controls. The survivors were divided into two treatment groups: 36 patients after chemotherapy containing anthracyclines (ANT) and 33 patients after chemotherapy without anthracyclines (nonANT). Levels of NTproBNP were measured by using the Elecsys 2010 immunoassay analyzer (Roche Diagnostics). Echocardiography using M-mode, two-dimensional and Doppler measurements were performed on the same day as blood samples were obtained for NTproBNP analysis in survivors.. Serum levels of NTproBNP were significantly higher in the ANT group than in controls (median 51.52 vs 17.37 pg/ml; p=0.0026). Survivors exposed to ANT had significantly increased levels of NTproBNP compared with patients treated without ANT (median 51.52 vs 12.24 pg/ml; p=0.0002). Female exposed and unexposed survivors had significantly higher NTproBNP levels than males. Four of the 36 survivors (11%) treated with ANT and two of the 33 patients (6%) not exposed to ANT had abnormal NTproBNP levels. Although no patient had echocardiographic abnormalities, significant differences were found in values of left ventricular ejection fraction (LVEF) and deceleration time (DT) between survivors treated with or without anthracyclines.. Higher levels of NTproBNP detected in childhood leukemia survivors after low anthracycline cumulative doses might reflect an initial stage of ANT cardiotoxicity before the development of echocardiographic abnormalities. Although the current studies support NTproBNP as one of the best available biochemical markers of late anthracycline cardiotoxicity, a possible strategy toward further improvement and combination with other cardiac biomarkers and novel echocardiographic methods should be explored in additional studies.

Topics: Adolescent; Anthracyclines; Biomarkers; Child; Child, Preschool; Echocardiography; Female; Heart Injuries; Humans; Infant; Male; Natriuretic Peptide, Brain; Peptide Fragments; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survivors

The study objective was to assess plasma N-terminal-pro-brain natriuretic peptide (BNP) levels and to evaluate left ventricular mass as well as left ventricular systolic and diastolic functions in 44 children who had undergone treatment for acute lymphoblastic leukaemia and Hodgkin's lymphoma, with regard to gender, age at disease onset, time that had passed since therapy completion, cumulative dose of antracyclines and mediastinal radiotherapy applied.. The median levels of pro-BNP were found to be higher in the whole study group as compared with the control (55.9 ± 53.1 ng/mL vs. 38.5 ± 47.7 ng/mL, P= 0.059). The pro-BNP values >80.0 ng/mL (standard deviation score (SDS)) were noted in 11/44 patients, including those exceeding 115.0 ng/mL (2 SDS) - in 6/44 patients.. No correlation was observed of pro-BNP levels with the accumulated dose of antracyclines (r=-0.42, P= 0.79) or mediastinal radiotherapy (r= 0.197, P= 0.2). However, negative correlation was found between pro-BNP and the time that had passed since therapy completion (r=-0.378, P= 0.009). In echocardiography, shortening and ejection fractions remained normal, whereas the indexed stroke volume was below 40 mL/m(2) in 16/44 patients. The E/A index below 1.5 was found in 6/44 cases. The left ventricular systolic mass remained within the normal range. Negative correlation was noted between isovolumetric diastolic time and pro-BNP level.. Increased levels of pro-BNP after anti-cancer treatment with the involvement of cardiotoxic substances may indicate the first symptoms of myocardial dysfunction, despite the lack of major echocardiographic disorders.

Topics: Adolescent; Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Chemoradiotherapy; Child; Diastole; Echocardiography; Female; Follow-Up Studies; Heart Ventricles; Hodgkin Disease; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiation Injuries; Stroke Volume; Ventricular Function, Left; Young Adult

The purpose of this study is to evaluate echocardiographically determined cardiac functions with serum levels of brain natriuretic peptide (BNP), cardiac troponin I (cTnI) and total antioxidant status (TAOS) in childhood leukemia treated with chemotherapeutics containing anthracyclines.. A study group of 29 patients who have been followed for acute lymphoblastic leukemia (ALL) and administered a treatment protocol containing chemotherapy of anthracyclines were included in the analysis. Levels of BNP, cTnI and TAOS were studied in serum samples of the patients.. We demonstrated that as the drug dosage increased, systolic ejection fraction (EF) and shortening fraction (FS) values decreased (EF r2=0.2327, FS r2=0.251). On the other hand, increased dosage of anthracycline therapy was associated with significant raise in plasma BNP levels (r2=0.246) and significant decrease in serum TAOS levels (r2=0.317) without any change in serum cTnI levels.. Our study suggest that serum TAOS and BNP levels may be useful as an early and sensitive indicator of anthracycline induced cardiotoxicity.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Antioxidants; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infant; Male; Natriuretic Peptide, Brain; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Stroke Volume; Troponin I; Ultrasonography

The incidence of subclinical cardiotoxicity following anthracycline treatment for childhood cancer varies according to the method used for its detection. The aim of the study was to document the prevalence of left ventricular myocardial mass (LVM) reduction and its possible association with plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in asymptomatic children treated with anthracyclines.. Nineteen asymptomatic children who had received anthracyclines during their treatment for cancer were evaluated. They had received an equivalent of doxorubicin dose 240 mg/m2 (22-1200 mg/m2) on average 3.9 years (0.6-8.3) before (median age at diagnosis 3.8 years). The LVM was determined by M-Mode echocardiography and compared to the expected value, obtained from the regression equation of LVM on height of a group of 160 healthy children. Additionally the patients' plasma NT-pro BNP levels were determined.. A high prevalence of reduced LVM associated with increased NT-proBNP levels was found. The average LVM value was -14.4% (+/-4.9) lower than expected whereas fourteen patients (73%) had a lower LVM than predicted. The NT-pro BNP levels in patients with reduced LVM were significantly higher than those measured in patients without LVM reduction (0.316+/-0.02 versus 0.17+/-0.01 pmol/ml respectively, p=0.009). A cut off NT-pro BNP level of 0.2 pmol/ml could differentiate patients with LVM reduction from those with normal or greater than expected LVM.. The association of higher NT-proBNP levels with reduced LVM in asymptomatic children after anthracycline administration could be an early indication of subclinical cardiotoxicity.

Topics: Adolescent; Anthracyclines; Child; Child, Preschool; Doxorubicin; Female; Heart Diseases; Heart Ventricles; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Precursor Cell Lymphoblastic Leukemia-Lymphoma