natriuretic-peptide--brain and Leukemia

Cardiac failure is a known complication of haemopoietic stem cell transplantation (HSCT) and is often difficult to diagnose as patients may have multiple medical problems. Since brain natriuretic peptide (BNP) is largely a hormone of cardiac ventricular origin and is released early in the course of ventricular dysfunction, we have examined the value of serial plasma BNP levels for detecting cardiac failure in patients undergoing cytotoxic conditioning for HSCT. Fifteen patients undergoing HSCT were evaluated (10 undergoing autologous HSCT; five undergoing allogeneic HSCT). BNP was measured by radioimmunoassay prior to therapy and weekly for 5 weeks. Seven patients had a significant rise in BNP level (above a previously established threshold of 43 pmol/l associated with cardiac failure), occurring 1-4 weeks post commencement of conditioning. In three of these patients, cardiac failure was subsequently diagnosed clinically 3, 9 and 23 days after a BNP level of 43 pmol/l had been detected. These three patients had the highest peak BNP levels for the group and in each case elevation in BNP level occurred for a period exceeding 1 week. Although numbers were relatively small, a BNP >43 pmol/l was significantly associated with the inclusion of high-dose cyclophosphamide in the preparative regimen (P = 0.02). BNP levels showed no relationship to febrile episodes. In conclusion, these results show that plasma BNP may be used as a marker for early detection of cardiac dysfunction in patients undergoing HSCT, particularly if levels are increased for periods exceeding 1 week. Measurement of BNP during HSCT may be helpful in patients at risk of cardiac failure, in complex clinical situations and in monitoring the cardiotoxicity of preparative regimens.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Lymphoma; Middle Aged; Natriuretic Peptide, Brain; Rhabdomyosarcoma; Transplantation Conditioning; Ventricular Dysfunction, Left

The use of posttransplant cyclophosphamide (PT-Cy) has contributed significantly to the success of haploidentical hematopoietic cell transplantation (HCT). Furthermore, several studies have shown promising results in the human leukocyte antigen-matched setting. However, the use of high-dose cyclophosphamide has been associated with the development of cardiomyopathy. There is a paucity of data concerning posttransplant cardiac complications in patients undergoing PT-Cy-based HCT.. A retrospective analysis of 176 patients undergoing HCT with PT-Cy was performed. The overall survival, left ventricular ejection fractions, brain natriuretic peptide levels, and cardiac comorbidities were reviewed. The associations between comorbidities and the onset of heart failure were assessed with a Cox proportional hazards model.. Pretransplant cardiomyopathy was found in 16 patients (9.1%) but had no effect on their posttransplant overall survival. Thirty-five patients (21.9%) developed posttransplant cardiomyopathy, which correlated with increased mortality, but this was not statistically different from the frequency-matched non-PT-Cy cohort. The majority of these cardiomyopathies occurred in the setting of an infectious milieu. An age greater than 60 years and an HCT comorbidity index score equal to or greater than 4 were the only risk factors that correlated with posttransplant cardiomyopathy.. The presence of pretransplant cardiomyopathy does not negatively affect overall survival for patients who undergo HCT with PT-Cy. Furthermore, cardiomyopathy in PT-Cy patients is not caused by PT-Cy but is mostly concurrent with infectious complications and is associated with reduced overall survival. Traditional cardiovascular risk factors do not fully predict the occurrence of posttransplant cardiomyopathy. Future research is required to unravel predictive factors for cardiomyopathy after PT-Cy-based HCT. Cancer 2017;123:1800-1809. © 2017 American Cancer Society.

Topics: Adult; Aged; Anemia, Aplastic; Antineoplastic Agents, Alkylating; Bone Marrow Diseases; Cardiomyopathies; Cardiovascular Diseases; Comorbidity; Cyclophosphamide; Echocardiography; Female; Heart Failure; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Lymphoma; Male; Middle Aged; Multiple Myeloma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Retrospective Studies; Stroke Volume; Survival Rate; Transplantation Conditioning; Young Adult

The goal of this study was to determine if low to moderate doses of anthracycline-based chemotherapy (Anth-bC) are associated with subclinical cardiovascular (CV) injury.. Cancer survivors who receive Anth-bC experience premature CV events. It is unknown whether low to moderate doses of anthracyclines promote early subclinical CV disease manifested by deteriorations in left ventricular ejection fraction (LVEF) or increases in aortic stiffness, or if these doses are associated with changes in quality of life (QOL).. In 53 men and women with breast cancer, leukemia, or lymphoma, we assessed left ventricular volumes, LVEF, circumferential strain, aortic pulse wave velocity, late gadolinium enhancement, serum B-type natriuretic peptide, troponin I, and the impact of treatment on QOL before and 1, 3, and 6 months after receipt of Anth-bC.. Participants averaged 50 ± 2 (range 19 to 80) years in age, 58% were women, 17% were black, and they each received a range of 50 to 375 mg/m(2) of doxorubicin-equivalent chemotherapy. Left ventricular end-systolic volume (48 ± 3 ml to 54 ± 3 ml; p = 0.02), left ventricular strain (-17.7 ± 0.4 to -15.1 ± 0.4; p = 0.0003), pulse wave velocity (6.7 ± 0.5 m/s to 10.1 ± 1 m/s; p = 0.0006), and QOL deterioration (15.4 ± 3.3 to 28.5 ± 3.9; p = 0.008) increased, whereas LVEF (58 ± 1% to 53 ± 1%; p = 0.0002) decreased within 6 months after low to moderate doses of Anth-bC. All findings persisted after accounting for age, gender, race (white/black), doxorubicin-equivalent dose, doxorubicin administration technique, comorbidities associated with CV events, and cancer diagnosis (p = 0.02 to 0.0001 for all). There were no new late gadolinium enhancement findings after 6 months.. In these study patients, low to moderate doses of Anth-bC were associated with the early development of subclinical abnormalities of cardiac and vascular function that in other populations are associated with the future occurrence of CV events.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Breast Neoplasms; Cardiovascular Diseases; Female; Humans; Leukemia; Lymphoma; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Pulse Wave Analysis; Quality of Life; Risk Factors; Stroke Volume; Surveys and Questionnaires; Time Factors; Troponin I; Vascular Stiffness; Ventricular Function, Left; Young Adult

Clinical cardiac complications in oncologic patients may develop from subclinical myocardial damage. Biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and troponin T (cTnT) have been hypothesized to reflect preclinical cardiotoxicity earlier than echocardiography. The aim of this study was to assess prospectively the serial values of these cardiomarkers in leukemia patients treated with allogeneic hematopoietic stem cell transplantation (HSCT).. Twenty-one patients who were treated with allogeneic HSCT for acute leukemia at mean age of 32.8 years (range: 19-58) were studied. The conditioning regimen included high-dose cyclophosphamide in combination with total body irradiation (TBI) or busulphan. All patients were treated with anthracyclines earlier (median cumulative dose 250 mg/m, range: 150-580).. Cardiomarkers were measured before the preparative regimen (PR) and on days 1, 14 and 30 after HSCT. Their cardiac systolic function was assessed before PR, and 1-2 months after HSCT by echocardiography.. The differences in NT-proBNP before PR and after HSCT were statistically significant (p<0.001). The values of cTnT before and after HSCT were also significantly different (p=0.005). Persistent abnormalities (30 days after HSCT) of NT-proBNP levels were found in 19/21 patients (90.5 %) and of cTnT levels in 10/21 patients (47.6 %). The median cTnT concentrations were higher in patients treated with TBI than in patients without TBI (p=0.013). The median NT-proBNP values were higher in patients pretreated with higher cumulative doses of anthracyclines (>250 mg/m vs ≤250 mg/m) Cardiac symptoms developed in 3/21 (14.3 %) patients (Tab. 1, Fig. 3, Ref. 36).

Topics: Acute Disease; Adult; Biomarkers; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Transplantation Conditioning; Troponin T; Young Adult

Late cardiac complications in cancer survivors may develop from subclinical myocardial damage. Biochemical correlates of minimal myocardial changes can be analyzed using a commercially available rapid assay. Biomarkers are considered more sensitive markers of subclinical cardiotoxicity than conventional electrocardiographic and echocardiographic methods. The aim of this study was to determine the values of plasma N-terminal pro brain natriuretic peptide (NT-pro-BNP) and cardiac troponin T (cTnT) in asymptomatic childhood leukemia survivors after anthracycline therapy in comparison with healthy volunteers. The survivors also underwent a detailed echocardiography. Twenty six survivors of leukemia previously treated with anthracyclines with total cumulative dose 95-600 (median 221) mg/m(2) were evaluated. Analyses of cTnT and NT-proBNP from blood samples and echocardiography were performed 5-25 years after completion of therapy for childhood leukemia. Control group for biochemical analyses consisted of 22 age- and gender- matched apparently healthy volunteers. Values of NT-proBNP were significantly elevated in ANT group compared to controls (35.1 +/- 37.8 vs. 9.6 +/- 6.7 pg/ml, P<0.010). CTnT remained below the diagnostic cut-off values in both groups. All echocardiographic parameters of patients remained normal. In conclusion, differences in NT-proBNP values between patients treated with anthracyclines and healthy volunteers might signal an initial stage of anthracycline-induced myocardial damage. The potential of this biomarker to detect subclinical anthracycline-induced myocardial alterations before development of echocardiographic and clinical changes is promising.

Topics: Adolescent; Adult; Anthracyclines; Antineoplastic Agents; Biomarkers; Case-Control Studies; Child; Child, Preschool; Echocardiography; Female; Heart Diseases; Humans; Infant; Leukemia; Male; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Survivors; Treatment Outcome; Troponin T; Young Adult

Cardiotoxicity is a relatively frequent and potentially serious complication of antitumor treatment. Anthracyclines and other high-dose chemotherapy represent the greatest risk. The aim of the study was to assess cardiotoxicity during preparative regimen (PR) and hematopoietic cell transplantation (HCT) in acute leukemia (AL) with biochemical markers - "N-terminal pro brain natriuretic peptide" (NT-proBNP), cardiac troponin T (cTnT) and creatine kinase MB (CK-MB mass).. Nineteen adult AL patients previously treated with anthracyclines--idarubicine, daunorubicine, mitoxantrone with standard doses for a cycle as 3 x 12 mg/m(2), 3 x 50 mg/m(2), 3 x 10 mg/m(2) accordingly were studied. PR consisted of high-dose cyclophosphamide (HD-C) in combination with busulphan or total body irradiation (TBI). Plasma NT-proBNP, cTnT and CK-MB mass concentrations were measured the day before PR, the day after PR, the day after HCT and 14 days after HCT.. Before PR, mean plasma NT-proBNP value was 106.3+/-55.7 ng/l. After PR, it increased to 426.1+/-391.5 ng/l. After HCT, a further increase to 847.6+/-780.6 ng/l was observed. Fourteen days after HCT, the mean NT-proBNP was 330.8+/-236.8 ng/l. The differences were statistically significant in comparison with the baseline values (p<0.01). The NT-proBNP elevations were more pronounced in patients with cumulative doses (CD) of anthracyclines above 450 mg/m(2) (p<0.05), in patients with PR containing HD-C and TBI (p<0.05). In all patients, plasma cTnT and CK-MB mass concentrations remained unchangable during PR and HCT.. Our results suggest that administration of PR and HCT is in most AL patients associated with acute neurohumoral activation (significant rise in NT-proBNP). Persistent NT-proBNP elevations, in our study in 12 (63.2%) patients, indicate subclinical cardiotoxicity (risk for development of heart failure) and require further follow-up. More pronounced NT-proBNP elevations in patients with higher CD of anthracyclines and in patients with PR containing combination of HD-C and TBI confirm that these therapeutic procedures seem to be more cardiotoxic and not very appropriate for patients with cumulation of risk factors for cardiotoxicity. Negative plasma cTnT and CK-MB mass concentrations show no detectable damage of cardiomyocyte structure during PR and HCT.

Topics: Acute Disease; Adult; Anthracyclines; Biomarkers; Creatine Kinase, MB Form; Echocardiography; Female; Heart Diseases; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Male; Myeloablative Agonists; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Assessment of acute and chronic cardiotoxicity of anthracyclines in patients treated for acute leukemia (AL) with biochemical markers - "N-terminal pro brain natriuretic peptide" (NT-proBNP), cardiac troponin T (cTnT), creatine kinase MB (CK-MB mass), and echocardiography.. Twenty-six adult AL patients (mean age 46.2 +/- 12.4 years, 15 males) treated with 2-6 cycles of chemotherapy (CT) containing anthracyclines in the total cumulative dose of 464.3 +/- 117.5 mg/m2 were studied. Cardiac evaluation was performed at baseline, after first and last CT with anthracyclines and 6 months after CT.. Mean baseline NT-proBNP concentration was 117.7 +/- 46.4 ng/L (slightly elevated in 3 patients). After first and last CT, NT-proBNP elevations to 299.7 +/- 176.2 ng/L and 287.1 +/- 147.4 ng/L were observed, respectively. Six months after CT, mean NT-proBNP concentration was 362.5 +/- 304.9 ng/L (elevated in 16 patients). Changes in NT-proBNP were significant in comparison with the baseline values (p < 0.001). Six months after CT, two patients with marked NT-proBNP elevations during CT developed treatment-related cardiomyopathy with symptoms of heart failure. NT-proBNP correlated with systolic and diastolic LV dysfunction on echocardiography (r = 0.514; p < 0.01) and (r = 0.587; p < 0.01). CTnT concentrations were negative (bellow 0.01 microg/L) during CT in all patients. Six months after CT, delayed cTnT positivity occurred in 3 patients. CK-MB mass remained within the reference range in all patients.. Our study shows that anthracycline treatment is associated with acute and chronic neurohumoral activation of cardiac dysfunction that is manifested by a significant increase in NT-proBNP. It seems that NT-proBNP could be useful in the early detection of anthracycline cardiotoxicity. CTnT negativity during anthracycline treatment suggests that anthracyclines, even in higher cumulative doses, do not cause detectable acute injury to cardiomyocyte structure. Further studies using more sensitive markers of cardiac damage will be needed in this context.

Topics: Acute Disease; Adult; Anthracyclines; Biomarkers; Creatine Kinase, MB Form; Echocardiography; Female; Heart Diseases; Humans; Leukemia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Troponin T

Anthracyclines are well established as highly efficacious antineoplastic agents for childhood malignancy, but they frequently cause dose-related cardiotoxicity. For this reason, children who have received anthracyclines need periodical cardiac evaluation. The plasma levels of B-type natriuretic peptide (BNP) have been shown to increase in proportion to severity of cardiac dysfunction. N-terminal BNP (NT-pro-BNP) is secreted from the cardiac ventricles in response to volume expansion and pressure overload. The aim of our study was to investigate whether plasma levels of NT-pro-BNP and cardiac troponin I (cTnI) can be used as specific markers for doxorubicin-induced cardiotoxicity in children with malignancy.. We performed the study in Dicle University Hospital, Pediatric Hematology and Oncology clinic. Were measured plasma NT-pro-BNP and cTnI in 31 patients (14 boys and 17 girls) who received doxorubicin-containing chemotherapy for their malignancy at cumulative doses of 30-600 mg/m2, between October 2000 and December 2004. Cardiac evaluation of the patients included recording of electrocardiography and assessment of systolic and diastolic functions of the heart by echocardiography.. Of the 31 patients, 4 (12.9%) had left ventricular dysfunction as assessed by echocardiography. Plasma NT-pro-BNP levels in these patients were significantly elevated in comparison with healthy controls (p<0.001). Plasma NT-pro-BNP levels were significantly elevated in patients with cardiac dysfunction when compared with normal cardiac function (p<0.008). The cTnI levels were found under normal value in all patients.. Measurement of NT-pro-BNP level may be an easy and practical tool, and during treatment may allow earlier-identification of individuals at risk for monitoring cardiac damage. Plasma NT-pro-BNP concentration may be a useful and sensitive indicator of cardiac dysfunction in children receiving doxorubicin therapy.

Topics: Adolescent; Antibiotics, Antineoplastic; Cardiomyopathies; Case-Control Studies; Child; Child, Preschool; Doxorubicin; Female; Humans; Leukemia; Lymphoma; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin I; Ultrasonography

Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.

Topics: Acute Disease; Adult; Aged; Antibiotics, Antineoplastic; Atrial Natriuretic Factor; Biomarkers; Cardiac Output, Low; Daunorubicin; Female; Heart Diseases; Heart Failure; Heart Function Tests; Humans; Leukemia; Male; Middle Aged; Natriuretic Peptide, Brain; Statistics, Nonparametric