calca-protein--human and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Disruption of deoxyribonucleic acid (DNA) methylation patterns has emerged as one of the possible origins of leukemogenesis. Calcitonin (CALCA) gene is a hot-spot for gene hypermethylation in acute leukemias. This study aimed to systematically analyze the methylation status of CALCA gene in pediatric acute leukemia using methylation-specific polymerase chain reaction (MSP) and assess its value as a potential prognostic biomarker. The study population consisted of 70 children divided into; 35 acute myeloblastic leukemia (AML) and 35 acute lymphoblastic leukemia (ALL) patients. CALCA gene was found to be hypermethylated in 54.3% of AML and 65.7% of ALL patients. CALCA hypermethylation was neither correlated to any of the clinicopathologic characteristics of patients, standard prognostic factors nor response to induction therapy (P>0.05). Hypermethylated AML and ALL patients displayed poorer clinical outcome when compared with hypomethylated counterparts as evidenced by high relapse and mortality rates with the occurrence of early relapse (P<0.05). The estimated overall and disease-free survival rates at 2.5-years were significantly shorter for hypermethylated patients in both groups (P<0.01). Our results suggest that CALCA gene methylation pattern is an independent prognostic factor in pediatric acute leukemia that could characterize a group of patients with enhanced risk of relapse and death.

Topics: Adolescent; Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Cytogenetic Analysis; DNA Methylation; Female; Gene Expression Profiling; Humans; Infant; Leukemia, Myeloid, Acute; Male; Polymerase Chain Reaction; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Protein Precursors; Survival Analysis; Treatment Outcome

The aim of this study was to assess the value of procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-a), interleukin (IL)-1b, IL-8, and soluble TNF receptor II (sTNFRII) in early and rapid diagnosis of infection in neutropenic children with acute lymphoblastic leukemia (ALL) and to distinguish bacterial from viral infections.. The study included five groups (A, B, C, D, and E) of children with ALL undergoing intensive chemotherapy. Groups A and B consisted of neutropenic children with bacterial and viral infection, respectively. Groups C and D consisted of nonneutropenic children with bacterial and viral infection, respectively. Group E consisted of children without neutropenia and without fever.. In all groups, blood samples were collected upon admission and then for 7 days on a daily basis. Levels of CRP, PCT, TNF-a, IL-1b, IL-8, and sTNFRII were determined in all blood samples.. We found a highly significant difference in PCT levels between bacterial and nonbacterial episodes. Sensitivity and specificity of PCT were 94 and 96.5%, respectively.. Serial measurement of PCT levels on a daily basis seems to be helpful for early prediction of severe bacterial infections, monitoring febrile episodes regarding response to antibiotic therapy, and early detection of complications in the infectious process.

Topics: Adolescent; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Fever; Humans; Infant; Interleukin-1beta; Interleukin-8; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Precursors; Receptors, Tumor Necrosis Factor, Type II; ROC Curve; Tumor Necrosis Factor-alpha

Procalcitonin has proven to be a sensitive inflammatory marker in non-neutropenic patients. The aim of this study was to determine and compare Procalcitonin with other inflammatory markers in the serum of immunosuppressed children with haematological malignancies; and to assess the predictive value of these mediators in distinguishing between bacterial and non-bacterial infection.. The study included 37 children with acute lymphoblastic leukaemia undergoing intensive chemotherapy. They were divided into 3 groups, A, B and C. Group A consisted of 29 neutropenic children with 94 febrile episodes, group B of 20 neutropenic children with 56 afebrile episodes and group C of 13 non-neutropenic children with 58 afebrile episodes. Serial serum levels of PCT, C-Reactive Protein, Neopterin, Interleukin-6 and NO2/NO3 were all determined on a day-to-day basis for 7 consecutive days. In serum the concentrations of CRP was determined by nephelometry, of PCT by immunoluminescence and of Neopterin, IL-6 and NO2/NO3 by ELISA method.. According to our results the Procalcitonin concentration increased rapidly in patients with microbial infection; the response was detectable within 24 hs of the onset of fever due to microbial infections. Procalcitonin is a specific and sensitive marker of microbial infection in patients with neutropenic fever. The markers, C-Reactive Protein, Interleukin-6 and NO2/NO3 may not help to identify infections and distinguish the etiology of infection in neutropenic febrile children with acute lymphoblastic leukaemia.

Topics: Adolescent; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Enzyme-Linked Immunosorbent Assay; Humans; Immune Tolerance; Infant; Interleukin-6; Neopterin; Nephelometry and Turbidimetry; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Protein Precursors

Neutropenia as a state of immunosuppression is probably the major problem in patients suffering from acute lymphoblastic leukaemia undergoing intensive chemotherapy. Fever is frequent in neutropenic patients and often related to infection. Clinically, the presence of infection in patients with neutropenia may be difficult to establish, because there are usually few signs of infection. The aim of this work was to study sensitive markers for early diagnosis of microbial infection in neutropenic children undergoing intensive chemotherapy as a treatment for acute lymphoblastic leukaemia. The study included three groups (A, B and C) of children with acute lymphoblastic leukaemia and neutropenia. Group A consisted of 29 children with febrile neutropenia and microbial infection, aged 1-14 years (5.8+/-2.9), 11 boys and 18 girls; Group B of 38 children with febrile neutropenia without microbial infection, aged 2-14 years (6.8+/-3.1), 14 boys and 24 girls; and Group C of 53 children with neutropenia without fever and without infection, aged 1-14 years (5.9+/-2.1), 21 boys and 32 girls. Blood samples were collected upon admission and before the start of any antimicrobial treatment. The samples were used for blood culture, serological tests, leukocyte count and analysis of levels of C-reactive protein, procalcitonin, total adenosine deaminase (ADA) activity and its isoenzymes, ADA-1 and ADA-2. According to our results the procalcitonin levels and total ADA activity discriminated best between neutropenic febrile (Groups A and B) and neutropenic afebrile episodes (Group C). In conclusion, this study suggests procalcitonin and total ADA activity as two easily measurable and cost effective markers for the assessment of immune response in febrile neutropenic patients with acute lymphoblastic leukaemia.

Topics: Adenosine Deaminase; Adolescent; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Fever; Humans; Infant; Male; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Precursors

Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions to bacterial infections. The main aim in this study was to determine the diagnostic value of PCT in predicting the clinical severity of febril neutropenic attacks, compare it with that of C-reactive protein (CRP), and clarify its importance in culture-positive attacks.. Between February 2001 and April 2002, 36 patients who were neutropenic due to various hematologic disorders and febrile were entered into the study. Blood samples were obtained on the first day of fever for the measurement of serum PCT and CRP levels.. In clinically severe neutropenic fever attacks, means of serum PCT and CRP levels were measured as 0.93+/-1.33 ng/mL and 67+/-24 mg/L, while they were 0.37+/-0.23 ng/mL and 32+/-19 mg/L in clinically mild ones (p = 0.033 and p < 0.001). On the other hand, no statistical significance was found between culture-positive and negative attacks when either serum PCT or CRP levels were taken into consideration (p = 0.133 and p = 0.141). The specificity and positive predictive value of the serum PCT test for severe febrile neutropenia was higher than that of the serum CRP test (0.80 vs. 0.57 and 0.50 vs. 0.39). However, sensitivity and negative predictive value for CRP were higher than the values for PCT (1.00 vs. 0.40 and 1.00 vs. 0.73). Diagnostic value and positive likelihood ratio of CRP for severe febrile neutropenia were higher than those of PCT (71 vs. 67 and 2.32 vs. 2.00).. PCT and CRP are comparable with each other in prediction of the clinical severity of febrile neutropenic attacks. Furthermore, serum CRP levels correlate with the duration of fever.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Humans; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Protein Precursors