calca-protein--human and Graft-vs-Host-Disease

Infections are one of the most common complications after hematopoietic stem cell transplantation (HSCT). Diagnosis is established by analysis of clinical symptoms and results of diagnostic tests such as biochemical panels, microbiological cultures, and visual diagnostics. As the microbiological cultures yield positive results in only some patients and visual diagnostics might miss the infectious source, the diagnosis and proper treatment often depends on clinical assessment supported by laboratory test results. The most commonly used makers of inflammation include C-reactive protein and procalcitonin. However, these tests have serious limitations when used in patients after HSCT. The drugs used in conditioning, neutropenia, and graft-versus-host disease might influence the results of the tests and misguide the physician. In this review, we summarize the current knowledge on profiles of expression of basic markers of inflammation used in clinical practice in patients after HSCT.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Communicable Diseases; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Inflammation; Inflammation Mediators; Lung Diseases; Mucositis; Predictive Value of Tests; Protein Precursors; Risk Factors; Time Factors; Transplantation Conditioning; Treatment Outcome

Serum procalcitonin (PCT) has become a routinely utilized parameter with a high prediction value of the severity of bacterial infectious complications and their immediate outcomes. Whereas the utility of PCT in differentiating between bacterial and viral infection is generally accepted, its significance in fungal infections has yet to be determined. The aim of the study was to determine the role of PCT testing in patients at high risk for invasive fungal infections.. Immunocompromised hematological patients undergoing cyclic chemotherapy treatment or allogeneic hemopoietic stem cell transplantation with infectious complications in which the infectious agents were identified during the disease course were evaluated. In patients with bacterial infection, positive hemocultures were documented, and in patients with fungal infection, the presence of either proven or probable disease was confirmed according to Ascioglu criteria. C-reactive protein (CRP) and PCT were prospectively assessed from the day following fever onset, for four consecutive days.. Overall, 34 patients were evaluated, 21 with bacterial and 13 with fungal infections. Significant elevations of CRP concentrations (i.e., above the upper normal limit) were observed in all patients, with a tendency toward higher levels in bacterial (both gram-positive [Gr+] and Gr-negative [Gr-]) than in fungal infections. PCT levels were significantly elevated in patients with bacterial infections (e.g., predominantly in Gr- compared to Gr+), whereas in patients with fungal infections, we identified minimal or no PCT elevations, p < 0.01. For the fungal infections, according to constructed receiver operating characteristic curves, a combination of PCT <0.5 μg/L and CRP 100-300 mg/L offers the best specificity, sensitivity and positive and negative predictive values (81, 85, 73, and 89 %, respectively).. Altogether, our data suggest that the finding of substantially elevated CRP combined with low PCT in immunocompromised patients may indicate systemic fungal infection. The use of this combination might simplify the diagnostic process, which otherwise can often be lengthy and arduous.

Topics: Adult; Aged; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Middle Aged; Mycoses; Predictive Value of Tests; Protein Precursors; ROC Curve; Young Adult

Hematopoietic stem-cell transplant is a curative therapy for several malignant and nonmalignant disorders. The purpose of this study was to investigate the association of serum levels of high-sensitivity C-reactive protein and procalcitonin with complications such as acute graft-versus-host disease, veno-occlusive disease, and infection after hematopoietic stem-cell transplant.. Serum high-sensitivity C-reactive protein and procalcitonin levels were sequentially measured with an enzyme-linked immunosorbent assay and a semiquantitative immunochromatographic assay in 35 patients who had undergone hematopoietic stem-cell transplant.. The high-sensitivity C-reactive protein serum level was increased in patients with acute graft-versus-host disease and in those with sepsis. Increased procalcitonin levels were associated only with bacterial infection. Only procalcitonin levels differentiated patients with infection from those with another transplant-related complication. Veno-occlusive disease did not alter C-reactive protein or procalcitonin levels.. Our results support theories that serum levels of high-sensitivity C-reactive protein and procalcitonin are biomarkers for transplantrelated complications such as graft-versus-host disease or infection and that the procalcitonin level can differentiate patients with infection from those with graft-versus-host disease.

Topics: Adolescent; Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Diagnosis, Differential; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Young Adult

Procalcitonin (PCT) is considered a sensitive and specific diagnostic and prognostic marker of systemic bacterial infection, but its value is questionable in certain clinical conditions, particularly in hemato-oncological patients.. We analyzed PCT and C-reactive protein (CRP) levels in 56 patients of a pediatric hematology-oncology unit during 110 consecutive non-infectious febrile episodes related to administration of T-cell antibodies (group A; n = 22), alemtuzumab (monoclonal CD52 antibody, CAMPATH-1H/group B; n = 8), interleukin-2 (IL-2/group C; n = 41), prophylactic donor granulocyte transfusions (group D; n = 9), or to acute graft-versus-host disease (aGvHD/group E; n = 10) and compared the results with 20 episodes of Gram-negative sepsis (group F).. In the majority of the non-infectious episodes PCT and CRP increased to serum levels statistically indistinguishable from Gram-negative sepsis. Median peak levels of PCT (normal < 0.5 ng/ml)/CRP (normal < 8 mg/l) for groups A-F were 4.34/59.0 (A), 10.14/93.5 (B), 1.11/175.0 (C), 1.43/164 (D), 0.96/34.0 (E), and 8.14 ng/ml /126.0 mg/l (F). Highest single levels were observed in groups A and F.. PCT and CRP are of limited value as diagnostic markers of sepsis during T-cell-directed immunomodulatory treatment, granulocyte support, or acute GvHD.

Topics: Adolescent; Adult; Age Factors; Biomarkers; Biomarkers, Tumor; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child Welfare; Child, Preschool; Female; Graft vs Host Disease; Hematologic Diseases; Hematologic Neoplasms; Humans; Infant; Interleukin-2; Male; Prospective Studies; Protein Precursors

Procalcitonin (PCT) is an early marker of bacterial infection but little is known about its value in neutropenic allogeneic bone marrow transplant (BMT) recipients. We collected plasma from 12 recipients of T-cell-depleted HLA-matched related BMT recipients who had been treated preemptively with meropenem from the day after BMT for at least 15 days. PCT and C-reactive protein (CRP) concentrations were determined on BMT days 1, 5, 8, 12, and 15, and their relationship to inflammatory events (IE), including mucositis, microbiologically and clinically defined infections, acute graft-versus-host disease (GVDH), and unexplained fever, was then determined. The PCT concentrations were all low and never exceeded 4 microg/liter, unlike CRP concentrations, which spanned the full range up to 350 mg/liter. All patients had mucositis, and there was no significant difference between PCT concentrations associated with mucositis alone and those associated with an additional IE on BMT days 1 to 12. However, on BMT day 15, the mean concentrations of PCT were 0.37 +/- 0.05 microg/liter for the 10 patients that had an additional IE, compared with 0.11 +/- 0.03 microg/liter for the 2 patients with mucositis only (P = 0.012), and GVHD rather than infection was involved in six cases. PCT was also not a sensitive marker of gram-positive bacteremia or pulmonary aspergillosis. Thus, PCT is of little value in discriminating infections from other inflammatory complications that occur following allogeneic BMT.

Topics: Adult; Biomarkers; Bone Marrow Transplantation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Graft vs Host Disease; Humans; Infections; Inflammation; Male; Meropenem; Protein Precursors; Thienamycins; Transplantation, Homologous