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1.
Klin Onkol ; 36(4): 382-395, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37877531

RESUMEN

BACKGROUND: Pediatric-inspired protocols with prospective monitoring of minimal residual disease (MRD) are considered the standard of intensive treatment for adults with acute lymphoblastic leukemia (ALL). They have been used in the Czech Republic since 2007. PATIENTS AND METHODS: Two hundred and ninety-seven patients aged 18-65 years were treated at five hematology centers between 2007-2020 according to the GMALL 07/2003 protocol. This is a retrospective analysis of their treatment outcomes. RESULTS: In the Ph-negative cohort, 189 (93.1%) patients achieved complete remission, 5 (2.4%) patients were refractory, and early mortality was 3.0%. Seventy (34.5%) patients experienced relapse in a median of 10.6 months. Overall survival (OS) at 3 and 5 years was 63.5% and 55.9%, disease-free survival (DFS) at 3 and 5 years was 54.5% and 49.7%, respectively. Young adults under 35 years of age (P = 0.015), patients without initial CNS infiltration (P = 0.016), with MRD negativity before consolidation treatment (P < 0.001), transplanted in the 1st complete remission (P < 0.001), and subjects treated after 2012 (P = 0.05) had significantly better overall survival. In a multivariate analysis, MRD at week 11 was the only independent factor affecting OS (HR 3.06; P = 0.006). For DFS, baseline CNS infiltration (HR 2.08; P = 0.038) and MRD at week 11 (HR 2.15; P = 0.020) were significant. In the Ph-positive cohort, 84 (89.4%) patients achieved complete remission, 1 (1.0%) patient was refractory, early mortality was 4.3%. Twenty-six (27.7%) patients relapsed in a median of 8.6 months. Survival at 3 and 5 years was 57.2% and 52.4% for OS and 50.2% and 44.9% for DFS, respectively. Transplanted patients and patients diagnosed after 2012 had statistically better overall survival (P < 0.001). CONCLUSION: The introduction of pediatric-inspired protocols with treatment intensification according to MRD levels resulted in a significant improvement in the survival outcomes of adult patients with ALL.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto Joven , Humanos , Adulto , Estudios Retrospectivos , Estudios Prospectivos , República Checa/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Supervivencia sin Enfermedad , Neoplasia Residual/diagnóstico
2.
Exp Oncol ; 43(3): 234-236, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34591424

RESUMEN

AIM: To evaluate serum levels of selected cytokine receptors in B-cell precursor acute lymphoblastic leukemia (B-ALL) and their association with acknowledged prognostic factors, relapse-free survival (RFS) and overall survival (OS). MATERIALS AND METHODS: A total of 42 de novo adult B-ALL patients, 19 BCR/ABL positive, were included in this study. Soluble receptor α for IL-2 (sIL-2Rα), soluble receptor for IL-6 (sIL-6R), soluble receptor for TNF-α type I and II (sTNFR-1, sTNFR-2) and matrix metalloproteinase-9 (MMP-9) were measured by biochip array technology at diagnosis and in complete remission (CR). RESULTS: At diagnosis of B-ALL, we found significantly higher levels of sIL-2Rα, sIL-6R, sTNFR-1, sTNFR-2 and significantly lower levels MMP-9 in comparison with CR (p < 0.001 in all cases). BCR/ABL positive patients had higher levels of sIL-2Rα at diagnosis (r = 0.484; p = 0.014). Serum levels of evaluated cytokines were not associated with achievement of CR after one cycle of induction therapy, RFS or OS. CONCLUSION: Serum levels of all evaluated cytokines are significantly altered in newly diagnosed B-ALL reflecting activity of the disease. No significant correlations with response to first induction therapy, RFS or OS were found. Further studies with a longer follow-up will be needed.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Quimioterapia de Inducción/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Receptores de Citocinas/sangre , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Pronóstico , Tasa de Supervivencia , Adulto Joven
3.
Exp Oncol ; 36(4): 252-7, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25537219

RESUMEN

AIM: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in patients with newly diagnosed acute myeloid leukemia (AML) using biochip array technology. We searched for links between baseline levels and age, hyperleukocytosis, secondary origin of AML, resistance to induction therapy with cytarabine and daunorubicin and standard risk stratification according to cytogenetics and molecular genetics. METHODS: We evaluated the sera of 51 consecutive patients. Serum samples were analyzed by biochip based immunoassays on the Evidence Investigator analyzer. T-tests were used for statistical analysis. RESULTS: We found that higher age is associated with lower levels of interleukin (IL)-12. Patients with secondary disease were older, had higher levels of EGF and IL-7, and lower levels of E-selectin, IL-12 and IL-13. In hyperleukocytosis, the levels of IL-1ß, IL-2, TNF-α, VCAM-1, ICAM-1, -E-selectin and L-selectin were increased, whereas levels of IFN-γ and MCP-1 were decreased. In patients who failed to achieve complete remission after induction therapy, we found lower E-selectin and P-selectin levels. High risk patients had lower levels of IFN-γ. CONCLUSION: Some leukemic cell subpopulations have the ability to produce cytokines that modulate the microenvironment by inducing inflammation. This causes endothelial cells to be activated and overexpress adhesion molecules. Hyperleukocytosis and secondary origin of the disease are the major factors influencing the cytokine and adhesion molecule profile in newly diagnosed AML patients.


Asunto(s)
Moléculas de Adhesión Celular/sangre , Citocinas/sangre , Leucemia Mieloide Aguda/sangre , Adulto , Factores de Edad , Anciano , Resistencia a Antineoplásicos , Femenino , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Mutación , Inducción de Remisión , Translocación Genética
4.
Exp Oncol ; 36(1): 50-1, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24691286

RESUMEN

AIM: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in patients with newly diagnosed acute myeloid leukemia (AML) and in healthy subjects using biochip array technology. METHODS: A total of 15 AML patients and 15 healthy subjects (blood donors) were studied. Serum samples were analyzed by biochip based immunoassays on the Evidence Investigator analyzer. This approach allows multi-analytical determination from a single sample. T-tests were used for statistical analysis. RESULTS: In newly diagnosed AML patients, we found significant increase (p < 0.01) in serum VCAM-1, ICAM-1, E-selectin, L-selectin, and significant increase (p < 0.05) in serum IL-6, IL-8. No significant differences were found in the levels of other evaluated cytokines and adhesion molecules. CONCLUSION: Our results indicate that serum levels of specific cytokines and adhesion molecules (VCAM-1, ICAM-1, E-selectin, L-selectin, IL-6, IL-8) are significantly altered in patients with newly diagnosed AML, showing activity of the disease. Whether these alterations could serve as a prognostic marker for AML is not known. Further studies will be needed to define the potential role of these and additional markers in the risk stratification of AML.


Asunto(s)
Biomarcadores de Tumor/sangre , Moléculas de Adhesión Celular/sangre , Citocinas/sangre , Leucemia Mieloide Aguda/sangre , Adulto , Selectina E/sangre , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Selectina L/sangre , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Análisis por Matrices de Proteínas/métodos , Molécula 1 de Adhesión Celular Vascular/sangre
5.
Bratisl Lek Listy ; 114(12): 708-10, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24329509

RESUMEN

OBJECTIVES: The aim of the presented study was to assess plasma glycogen phosphorylase BB (GPBB) concentrations in acute leukemia patients treated with anthracycline containing chemotherapy. BACKGROUND: Anthracyclines represent the highest risk for development of cardiotoxicity. GPBB belongs to proposed biomarkers of cardiac injury with a very limited experience in this context. METHODS: Totally, 24 adult patients with acute leukemia were enrolled. Plasma GPBB concentrations were measured by ELISA at diagnosis (before chemotherapy), after first chemotherapy with anthracyclines and 6 months after the completion of treatment. The cut-off value for GPBB positivity was 10.00 µg/L as recommended by the manufacturer. RESULTS: Before chemotherapy, the mean plasma GPBB concentration was 5.25±3.81 µg/L, increased above the cut-off in 1 patient (4.2 %). After the first chemotherapy, the mean GPBB was 6.61±5.54 µg/L, positive in 7 (29.2 %) patients. Six months after treatment, the mean GPBB was 10.06±11.41 µg/L, positive in 8 (33.3 %) patients. Six months after treatment, we found a significant correlation between elevation in GPBB and diastolic left ventricular dysfunction on echocardiography (r=0.621; p<0.0001). The differences in plasma GPBB between healthy blood donors and patients treated for acute leukemia were statistically significant (p<0.01 in all cases). CONCLUSION: Our results suggested that GPBB could become a potential biomarker for detection of acute and chronic cardiotoxicity associated with anthracycline containing chemotherapy. The predictive value for development of treatment-related cardiomyopathy in future is not clear and will be evaluated during the follow-up. Further studies are needed to define the potential role of GPBB and other biomarkers in the assessment of chemotherapy-induced cardiotoxicity (Ref. 21). Text in PDF www.elis.sk.


Asunto(s)
Antraciclinas/efectos adversos , Glucógeno Fosforilasa/sangre , Cardiopatías/inducido químicamente , Leucemia Mieloide Aguda/tratamiento farmacológico , Antraciclinas/uso terapéutico , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Cardiopatías/enzimología , Humanos , Leucemia Mieloide Aguda/enzimología , Masculino , Persona de Mediana Edad
6.
Exp Oncol ; 35(3): 229-30, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24084464

RESUMEN

AIM: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in patients with acute lymphoblastic leukemia (ALL) and in healthy subjects using biochip array technology. This approach allows multi-analytical determination from a single sample. METHODS: A total of 15 ALL patients and 15 healthy subjects (blood donors) were studied. Serum samples were analyzed by biochip based immunoassays on the Evidence Investigator analyzer. T-tests were used for statistical analysis. RESULTS: Comparing cytokine and adhesion molecule levels in ALL patients and in healthy subject, we found significant increase in serum VCAM-1 (p < 0.000001), ICAM-1 (p < 0.0001), L-selectin (p < 0.0001), IL-8 (p < 0.001), MCP-1 (p < 0.01), and significant decrease (p < 0.01) in serum IL-3 and IL-4. CONCLUSION: Our results indicate that serum levels of specific cytokines and adhesion molecules (VCAM-1, ICAM-1, L-selectin, IL-8, IL-3, IL-4, MCP-1) are significantly altered in patients with newly diagnosed ALL, reflecting acti-vity of the disease. Further investigation is needed to establish if these alterations could be used as a prognostic indicator for ALL.


Asunto(s)
Moléculas de Adhesión Celular/sangre , Citocinas/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Análisis por Matrices de Proteínas/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
7.
Ann Clin Biochem ; 48(Pt 1): 38-40, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21098548

RESUMEN

BACKGROUND: The aim of our study was to monitor radiofrequency catheter ablation-induced myocardial damage by measuring high-sensitivity cardiac troponin T (hs-cTnT). METHODS: Serum concentrations of hs-cTnT (Elecsys 2010 system, Roche) were measured in 73 healthy blood donors and serially in 27 patients who had samples taken both before and 24 h after radiofrequency ablation (RFA) for atrioventricular nodal re-entry tachycardia (AVNRT), atrial fibrillation (AF) or right atrial flutter (AFL). RESULTS: Significant increases of hs-cTnT were seen in patients after RFA (AVNRT: P = 0.0115, AF: P = 0.0011, AFL: P = 0.0009). Postprocedural serum hs-cTnT correlated with the number of radiofrequency applications and with the duration of RFA procedure. Spearman's coefficient of rank correlation (r) were as follows: hs-cTnT versus RFA duration: r = 0.771 (P < 0.001); hs-cTnT versus number of pulses: r = 0.708 (P < 0.001). Patients with the diagnosis of AVNRT had lower serum hs-cTnT concentration after RFA compared with AFL (P < 0.0001) and AF (P < 0.0001) patients. CONCLUSIONS: Our data indicate that RFA causes a significant increase of serum hs-cTnT concentration that could be used to monitor myocardial injury.


Asunto(s)
Ablación por Catéter/efectos adversos , Lesiones Cardíacas/diagnóstico , Monitoreo Fisiológico/métodos , Troponina T/sangre , Fibrilación Atrial/terapia , Aleteo Atrial/terapia , Biomarcadores/sangre , Femenino , Lesiones Cardíacas/sangre , Humanos , Masculino , Persona de Mediana Edad , Miocardio , Proyectos Piloto , Taquicardia por Reentrada en el Nodo Atrioventricular/terapia
8.
Exp Oncol ; 32(2): 97-9, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20693970

RESUMEN

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 microg/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 microg/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.


Asunto(s)
Antineoplásicos/efectos adversos , Biomarcadores de Tumor/sangre , Corazón/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Adulto , Antineoplásicos/administración & dosificación , Forma MB de la Creatina-Quinasa/sangre , Proteína 3 de Unión a Ácidos Grasos , Proteínas de Unión a Ácidos Grasos/sangre , Glucógeno Fosforilasa/sangre , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/cirugía , Mioglobina/sangre , Troponina I/sangre , Troponina T/sangre
9.
Vnitr Lek ; 56(3): 176-82, 2010 Mar.
Artículo en Checo | MEDLINE | ID: mdl-20394203

RESUMEN

INTRODUCTION: We present two years' experience in the treatment of adult acute lymphoblastic leukemia (ALL) according to the German GMALL 07/2003 study protocol at CELL (Czech leukemia study group--for life) hematological centers in the Czech Republic. METHODS: A total number of 37 patients were included in this analysis. We evaluated complete remission and molecular remission rate, incidence of relapse, patients' status at the end of the follow-up period, incidence of chemotherapy-related adverse events and causes of death. A statistical analysis of risk factors affecting survival was carried out. RESULTS: Complete remission was achieved in 36 (97%) patients and molecular remission in 16 (62%) of 26 evaluable patients. Disease relapse occurred in 5 (14%) patients. At the end of the follow-up period with a median of 261 days, 28 (76%) patients were alive in complete remission, one (3%) with relapsed disease and 8 (22%) dead. Treatment toxicity resulted in death in 5 cases, relapse or progression of ALL in 3 patients. Adverse events most often followed consolidation I, induction phase I, consolidation II and induction phase II. Infectious complications in the context of febrile neutropenia, GIT mucositis and side effects of PEG-asparaginase were the most common adverse events observed. The toxicity of allogeneic transplantation was not unexpected, four (25%) patients died after transplantation. Two-year progression-free and overall survival were 66% and 70%, respectively. High risk ALL, age over 35 years, CNS infiltration, disease relapse and permanent minimal residual disease were identified as the major adverse prognostic risk factors. Practical experiences and possible pitfalls of the protocol are described in the discussion. CONCLUSION: Our initial impression is promising. The treatment is feasible, the results very good and the toxicity acceptable. Patients at high risk should be headed to allogeneic transplantation, since the results ofconsolidation chemotherapy alone are very poor in this group. We believe that this study protocol could become a standard adult acute lymphoblastic leukemia treatment in the Czech Republic.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Humanos , Persona de Mediana Edad , Inducción de Remisión , Adulto Joven
11.
Exp Oncol ; 31(2): 115-7, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19550402

RESUMEN

AIM: Monitoring of anthracycline-induced cardiotoxicity with electrocardiography (ECG) and comparing ECG changes with findings on echocardiography (ECHO). METHODS: A total of 26 adult acute leukemia patients (mean age 46.2 -/+ 12.4 years, 15 males) treated with 2-6 cycles of anthracycline-based chemotherapy (CT) were studied. Cardiac evaluation was performed at the baseline (before CT), after first CT, after last CT (cumulative anthracycline dose 464.3 -/+ 117.5 mg/m2) and circa 6 months after CT. Time ECG parameters, QRS voltage, presence of repolarization changes, arrhythmias and other abnormalities were evaluated. RESULTS: During treatment and follow-up, we found a statistical significant QTc interval prolongation - 414.7 -/+ 16.0 ms (before CT), 419.6 -/+ 21.6 ms (after first CT), 428.0 -/+ 16.2 ms (after last CT) and 430.1 -/+ 18.4 ms (6 months after CT). Significant QTc interval prolongation (> 450 ms) occurred in 3 patients after first CT, in 4 patients after last CT and in 5 patients within 6 months after CT. Significant total QRS voltage lowering in the limb leads (> 1.0 mV versus before CT) occurred in 3 patients after first CT, in 5 patients after last CT and in 6 patients within 6 months after CT. We found a statistically significant correlation between decreased QRS voltage, QTc interval prolongation and left ventricular (LV) dysfunction on ECHO. Repolarization changes associated with oncology treatment were present in 9 patients within 6 months after CT. CONCLUSION: Anthracycline treatment is associated with changes in electrical activity of the myocardium. Prolonged QTc interval represents a risk for development of malignant ventricular arrhythmias. Decreased QRS voltage and prolonged QTc interval after anthracycline treatment could correlate with LV dysfunction on ECHO. Further studies will be needed to prove whether these ECG changes could serve as an accessible and non-invasive screening method indicating LV dysfunction after anthracycline treatment.


Asunto(s)
Antraciclinas/efectos adversos , Antineoplásicos/efectos adversos , Arritmias Cardíacas/diagnóstico , Electrocardiografía , Corazón/efectos de los fármacos , Leucemia/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Arritmias Cardíacas/inducido químicamente , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
Exp Oncol ; 31(2): 121-2, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19550404

RESUMEN

AIM: Dimethylsulfoxide (DMSO) is the most frequently used agent for hematopoietic cell (HC) graft cryopreservation. This study aimed to monitor blood pressure and heart rate (HR) during HC graft infusion and assess the impact of cryopreservation with DMSO. METHODS: 153 HC graft infusions in 153 consecutive hematological patients (mean age 49.1 -/+ 12.6 years; 80 males) were evaluated. Cryopreservation with DMSO was used in 133 grafts (DMSO group). Twenty grafts were infused directly without cryopreservation (control group). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR were measured immediately before and after HC graft infusion. RESULTS: SBP and DBP increased significantly after graft infusions cryopreserved with DMSO ( p<0.0001 for SBP; p<0.01 for DBP). Increases (> 10mmHg) in SBP were seen in 42 (31.6%) patients; in DBP in 31 (23.3%) patients. Changes in HR were non-significant in DMSO group. Increases in BP and HR correlated with increasing DMSO dose (p<0.01; p<0.05, respectively). Changes in SBP, DBP and HR were non-significant in control group. CONCLUSION: HC graft infusions cryopreserved with DMSO could cause statistically significant increases in SBP and DBP, without changes in HR. These changes were mostly transient and asymptomatic, not requiring therapeutic intervention. However, they might cause complications, especially in patients with preexisting cardiovascular disease, who should be monitored closely during HC transplantation.


Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Criopreservación/métodos , Crioprotectores/efectos adversos , Dimetilsulfóxido/efectos adversos , Neoplasias Hematológicas/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Presión Sanguínea/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad
14.
Cas Lek Cesk ; 148(12): 591-6, 2009.
Artículo en Checo | MEDLINE | ID: mdl-20662394

RESUMEN

BACKGROUND: Multi-marker approach is recommended for rapid diagnostics and risk stratification of acute coronary syndrome. We tested the analytical performance of protein biochip technology for determination cardiac markers. METHODS: Analysis of cardiac markers: CK-MB mass, cTnl, myoglobin, glycogen phosphorylase BB (GPBB), heart type of fatty acid binding protein (h-FABP) and carbonic anhydrase III (CAIII) was performed by system Evidence Investigator (Randox). Analytical parameters of Cardiac array were tested. The Evidence Investigator results were compared with Elecsys 2010 (Roche) CK-MB mass and myoglobin methods. Markers of myocardial injury were determined in 28 blood donors, 28 patients with acute myocardial infarction diagnosis and 21 patients after chemotherapy containing anthracyclines (monitoring of cardiotoxicity). RESULTS: The Passing-Bablok regression shows statistically significant differences in results. The reasons for these differences are poor standardization of methods and discrepancies between calibrations. New substances h-FABP and GPBB are promising early markers of acute myocardial infarction and diagnostic sensitivity of h-FABP would be better than myoglobin test. These markers can be useful for monitoring of cardiotoxicity of anthracyclines. CONCLUSIONS: In future, the use of biochip technology in cardiology diagnostic represents an important challenge but it is a necessary standardization of immunochemical methods.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Biomarcadores/sangre , Análisis por Matrices de Proteínas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad
15.
Neoplasma ; 55(6): 532-7, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18999883

RESUMEN

Cardiac toxicity of preparative regimen (PR) containing high-dose Cyclophosphamide (120 mg/kg) followed by hematopoietic cell transplantation (HCT) was evaluated with 6 biomarkers of cardiac injury: N-terminal pro brain natriuretic peptide (NT-proBNP), creatine kinase MB (CK-MB mass), cardiac troponins (cTnT, cTnI), heart-type fatty acid binding protein (H-FABP), glycogen phosphorylase BB (GPBB). Twenty-three patients (mean age 44.5+/-10.6 years, 15 males) with acute leukemia were studied. All biomarkers were measured the day before PR, the day after PR, the day after HCT and 14 days after HCT. We found NT-proBNP elevations above 500 ng/L in 6 (26.1 %) patients after PR, in 9 (39.1 %) after HCT and in 7 (30.4 %) 14 days after HCT. GPBB became elevated (above 7.30 microg/L) in 5 (21.7 %) patients after PR, remained elevated in 5 (21.7 %) after HCT and in 2 (8.7 %) 14 days after HCT. A significant correlation between elevation in NT-proBNP and GPBB was found. Other markers remained within the reference range early after PR and HCT. Our findings show that administration of PR and HCT for acute leukemia is associated with acute neurohumoral activation of cardiac dysfunction (significant rise in NT-proBNP) and may lead to GPBB elevation. These changes could indicate acute cardiac toxicity due to treatment and require further follow-up. The predictive value for development of cardiomyopathy in the future is unclear. Further studies will be needed to define the potential role of new biomarkers in this context.


Asunto(s)
Biomarcadores/análisis , Ciclofosfamida/efectos adversos , Cardiopatías/inducido químicamente , Trasplante de Células Madre Hematopoyéticas , Leucemia/terapia , Enfermedad Aguda , Adulto , Femenino , Cardiopatías/diagnóstico , Cardiopatías/terapia , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/efectos adversos
17.
Exp Oncol ; 30(2): 157-9, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18566582

RESUMEN

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 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 microg/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 microg/L) in 1 (8.3%) patient after first and last CT and within 6 months after CT. CTnT remained negative (below 0.01 microg/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.


Asunto(s)
Antraciclinas/toxicidad , Biomarcadores de Tumor/biosíntesis , Corazón/efectos de los fármacos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Anciano , Biomarcadores/metabolismo , Femenino , Glucógeno Fosforilasa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo
18.
Exp Oncol ; 30(2): 160-2, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18566583

RESUMEN

AIM: To analyze the very early changes of diastolic LV function during and after chemotherapy (CT) in patients with newly diagnosed acute leukemia. METHODS: 26 patients with acute leukemia have been studied. The cardiac echo evaluation was performed at the baseline (before CT), after the first CT (mean cumulative anthracyclines dose 136.3-/+28.3 mg m(-2)), after the last CT (mean cumulative anthracyclines dose 464.3-/+117.5 mg m(-2)) and circa 6 months after the completion of CT. RESULTS: We found a significant decrease in LVEF (65.3-/+4.5' vs 60.2-/+5.7', p<0.01), the fractional shortening of the LV (34.8-/+3.7', vs 29.5-/+5.0', p<0.01), but the mitral flow rapid filling velocity (E-wave) was not changed (0.74-/+0.18 ms(-1), vs 0.67-/+0.17 ms(-1), p ns), and atrial filling velocity (A-wave) increased (0.66-/+0.15 ms(-1) vs 0.78-/+0.18 ms(-1), p<0.01). E/A ratio significantly decreased (1.18-/+0.35 vs 0.89-/+0.27, p<0.01). IVRT increased (71.5-/+11.6 ms vs 84.0-/+11.6 ms, p<0.01). DT E-wave velocity increased (162.3-/+25.8 ms vs 206.7-/+25.5 ms, p<0.01). After the first CT, the signs of LV diastolic dysfunction were detected in 5 (19.2') patients. 6 months after the last CT, two of these patients (7.7') developed LV systolic dysfunction with the clinical symptoms of heart failure. Six months after the last CT, 12 (46.2') patients developed the signs of LV diastolic dysfunction. CONCLUSION: Chemotherapy can induce early changes of diastolic left ventricular function. We consider using Doppler echocardiography as the election tool not only for baseline cardiologic screening but also for the monitoring of the earliest subclinical signs of cardiotoxicity.


Asunto(s)
Antraciclinas/uso terapéutico , Antineoplásicos/uso terapéutico , Diástole , Leucemia/tratamiento farmacológico , Función Ventricular Izquierda/efectos de los fármacos , Adulto , Antraciclinas/efectos adversos , Antineoplásicos/efectos adversos , Ecocardiografía Doppler/métodos , Femenino , Atrios Cardíacos/patología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo
19.
Neoplasma ; 55(4): 350-5, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18505348

RESUMEN

A pilot study analyses an effect of selected demographic, psychosocial and health aspects on quality of life (QoL) in multiple myeloma survivors treated with high-dose chemotherapy followed by autologous peripheral blood progenitor cell transplantation (PBPCT). The total number of respondents with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT between years 2001-2003 at the Department of Clinical Haematology of the 2nd Department of Internal Medicine of Charles University Hospital and Faculty of Medicine in Hradec Králové, Czech Republic was 32 (18 male, 14 female). The average age of respondents was 60 years old. The Czech version of an international generic European Quality of Life Questionnaire - Version EQ-5D was used. The effect of selected demographics, psychosocial and health aspects on QoL was determined by means of analysis of variance (ANOVA). The QoL questionnaires were evaluated by means of descriptive analysis. The above-mentioned aspects proved statistically significant dependence of QoL on respondents age and on smoking abuse. EQ-5D score (dimensions of QoL) and EQ-5D VAS (a subjective health condition) significantly decrease with increasing age and with smoking abuse. The effect of other aspects on QoL was not proven as statistically significant. Prevailing complaints in respondents with multiple myeloma were: 1. regular activity with complaints 81,2 % (26/32 respondents), 2. medium serious pain / discomfort 68,8 % (22/32 respondents), 3. movement with complaints 59 % (19/32 respondents), 4. medium serious anxiety / depression 59 % (19/32 respondents). The QoL in patients with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT was on low level (mean EQ-5D score was 68,9 %, mean EQ-5D VAS was 66,6 %). The results had shown that with an increasing age, the QoL of patients with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT, declines. The smokers and former smokers have lower QoL than non smokers. The global QoL in all studied patients with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT was on low level.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/psicología , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica , Calidad de Vida , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Retrospectivos , Factores Sexuales , Fumar , Sobrevivientes , Trasplante Autólogo
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