epiglucan and Leukemia

As culture-based methods for the diagnosis of invasive fungal diseases (IFD) in leukemia and hematopoietic SCT patients have limited performance, non-culture methods are increasingly being used. The third European Conference on Infections in Leukemia (ECIL-3) meeting aimed at establishing evidence-based recommendations for the use of biological tests in adult patients, based on the grading system of the Infectious Diseases Society of America. The following biomarkers were investigated as screening tests: galactomannan (GM) for invasive aspergillosis (IA); β-glucan (BG) for invasive candidiasis (IC) and IA; Cryptococcus Ag for cryptococcosis; mannan (Mn) Ag/anti-mannan (A-Mn) Ab for IC, and PCR for IA. Testing for GM, Cryptococcus Ag and BG are included in the revised EORTC/MSG (European Organization for Research and Treatment of Cancer/Mycoses Study Group) consensus definitions for IFD. Strong evidence supports the use of GM in serum (A II), and Cryptococcus Ag in serum and cerebrospinal fluid (CSF) (A II). Evidence is moderate for BG detection in serum (B II), and the combined Mn/A-Mn testing in serum for hepatosplenic candidiasis (B III) and candidemia (C II). No recommendations were formulated for the use of PCR owing to a lack of standardization and clinical validation. Clinical utility of these markers for the early management of IFD should be further assessed in prospective randomized interventional studies.

Topics: Antigens, Fungal; beta-Glucans; Biomarkers; Congresses as Topic; European Union; Galactose; Hematopoietic Stem Cell Transplantation; Leukemia; Mannans; Mycoses; Transplantation, Homologous

Topics: Antigens, Fungal; Aspergillosis; Aspergillus; beta-Glucans; Breath Tests; DNA, Fungal; Early Diagnosis; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Leukemia; Lung; Mannans; Neutropenia; Organ Transplantation; Transplantation Immunology

Invasive fungal infections (IFIs) are difficult to diagnose, especially early in the course of infection when antifungal therapy is most effective. There are two commercially available biomarker assays useful for detection of the IFIs most commonly seen in patients with hematologic malignancies, the galactomannan and beta glucan assays. The former is specific for aspergillosis, the latter positive for not only Aspergillus and Candida species, but several other clinically relevant fungal pathogens as well. Both have good assay performance characteristics, provide rapid test results, are widely available, can be assayed non-invasively, and are positive early in the course of infection, often before onset of signs and symptoms of infection. Adoption of these assays into clinical practice has led to reduced need to perform invasive procedures to obtain deep tissue to establish the diagnosis of invasive fungal infections. Improved survival rates from aspergillosis are, in part, due to earlier detection of infection and earlier therapy.

Topics: Acute Disease; Aspergillosis; Aspergillus; beta-Glucans; Biomarkers; Candida; Candidiasis; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Mannans; Transplantation, Homologous

Surveillance cultures may be helpful in identifying patients at increased risk of developing invasive candidiasis. However, only scant information exists on the effect of Candida colonization on serum levels of diagnostic biomarkers. This prospective surveillance study determined the extent of Candida colonization among pediatric cancer patients and its possible impact on serum levels of (1-3)-β-D-glucan (BDG), Candida mannan and Candida DNA.. A total of 1075 swabs originating from oropharynx (n = 294), nostrils (n = 600), rectum (n = 28), groin (n = 50), ear (n = 54), and axilla (n = 49) of 63 pediatric cancer patients were cultured for the isolation of Candida spp. Patients yielding Candida spp. from any sites were considered as colonized. Serum samples were collected from patients at the time of first surveillance culture for detection of BDG by Fungitell kit and Candida mannan by Platelia Candida Ag. Candida DNA was detected by using panfungal primers and identification was carried out by using species-specific primers and DNA sequencing.. Seventy-five (7.6%) swab cultures from 35 (55.5%) patients yielded Candida spp. These isolates included C. albicans (n = 62), C. dubliniensis (n = 8), C. glabrata and C. tropicalis (n = 2 each) and C. krusei (n = 1). Eleven patients were colonized at three or more sites. Eight of 36 serum samples from 6 colonized patients yielded BDG values higher than the currently recommended cut-off value of ≥80 pg/ml. However, none of the serum samples yielded Candida mannan levels ≥0.5 ng/ml and PCR test for Candida DNA was also negative in all the serum samples of colonized patients. During the study period, only two colonized patients subsequently developed candidemia due to C. tropicalis. Besides positive blood cultures, C. tropicalis DNA, BDG and Candida mannan were also detected in serum samples of both the patients.. The present study demonstrates that while mucosal colonization with Candida species in pediatric cancer patients is common, it does not give rise to diagnostically significant levels of Candida mannan or Candida DNA in serum specimens. However, BDG values may be higher than the cut-off value in some pediatric patients without clinical evidence of invasive Candida infection. The study suggests the utility of Candida mannan or Candida DNA in the diagnosis of invasive candidiasis, however, the BDG levels in pediatric cancer subjects should be interpreted with caution.

Topics: Adolescent; beta-Glucans; Candida; Candidiasis; Child; Child, Preschool; DNA, Fungal; DNA, Ribosomal Spacer; Humans; Infant; Leukemia; Mannans; Polymerase Chain Reaction; Proteoglycans

Persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients on broad-spectrum antibiotics have traditionally been treated with empirical antifungal therapy (EAFT). The lack of survival benefit seen with the use of amphotericin B deoxycholate (AmB-D) as EAFT has been attributed to its toxicities. More recently, newer, less toxic and more expensive antifungal agents such as the lipid formulations of AmB, the newer azoles (fluconazole, itraconazole and voriconazole) and caspofungin have been analysed in a number of EAFT trials. Compared with AmB-D the newer agents have superior safety but are of equivalent efficacy. This lack of survival advantage is related to the fact that the trigger for commencement of EAFT is late and non-specific. Thus, alternative approaches are required. New sensitive serological and molecular tests for the detection of Aspergillus antigens and genomic DNA have been developed and evaluated in accuracy studies. These tests have been incorporated into management strategies (i.e. pre-emptive strategies) to direct antifungal therapy. The pre-emptive approach has been shown to be safe and feasible but its impact on clinically important patient outcomes such as survival is less clear. Other advances include the introduction of effective, non-toxic mould-active antifungal prophylaxis and patient risk-group stratification. In this paper we provide new evidence-based algorithms for the diagnosis and treatment of PFUO in adult patients undergoing stem cell transplantation and chemotherapy for haematological malignancy which incorporate these newer diagnostic tests and are directed by the risk category of the patient and type of antifungal prophylaxis the patient is receiving.

Topics: Adult; Algorithms; Antifungal Agents; Antigens, Fungal; Aspergillus; beta-Glucans; Evidence-Based Medicine; Fever of Unknown Origin; Galactose; Humans; Leukemia; Mannans; Polymerase Chain Reaction; Recurrence; Stem Cell Transplantation; Tomography, X-Ray Computed

Topics: Antifungal Agents; Antigens, Fungal; Aspergillosis; beta-Glucans; Candidiasis; Chemoprevention; Humans; Leukemia; Proteoglycans; Triazoles

One of the advanced methodologies of the tumor therapy is the application of the so-called biological response modifiers used for activation of the endogenous antitumor mechanisms and combined with classical cytotoxic agents. The aim of this work was the investigation of the effect of sulfoethylated (1-->3)-beta-D-glucan (SEG) in the treatment of experimental murine leukoses in combination with cyclophosphamide (CPA) and its ability to modulate the activity of lysosomal enzymes in tumor tissues.. The solid forms of inoculated murine leukoses P388 and L1210/1 were transplantated to male DBA/2 mice. The therapy was performed by treating animals with CPA (Biokhimik, Saransk, Russia) alone or in combination with SEG (Institute of Chemistry, Slovak Academy of Sciences, Slovakia). CPA was administered in saline as a single intraperitoneal (ip) injection on the 10th day after tumor transplantation; SEG was administered to mice ip 3 days after tumor transplantation with the intervals in 3 days. The therapy effect was estimated by measuring of solid tumor volume. Activity of the cysteine proteases--cathepsins B and L--was measured fluorometrically using fluorescent substrates Z-Arg-Arg-MCA and Z-Phe-Arg-MCA (Sigma, USA), respectively. The apoptosis was estimated evaluating the number of cells with fragmented nuclei using optical microscope.. It has been demonstrated that application SEG leads to inhibition of tumor growth and potentiates therapeutic action of CPA, especially at repeated administrations during the whole treatment/observation At addition of SEG, therapeutic effect of a one-half reduced dose of CPA is equal or higher than that of the full dose. Therapeutic action of CPA and SEG on the studied tumors is realized predominantly through induction of apoptosis and is accompanied by a substantial increase of the activity of cysteine proteases cathepsins B and L in tumor tissues. The highest cathepsin B and cathepsin L activity in tumor tissue accompanied with the strongest inhibition of tumor growth. It is suggested that this phenomenon is due to the infiltration of the macrophages rich in the named enzymes into the tumor, where they phagocytize the apoptotic cells and tissue debris.. Utilization of this polysaccharide BRM, sulfoethylated (1-->3)-beta-D-glucan, might potentially enhance efficiency of antitumor therapy with standard cytostatics without a need of substantial increase of their dosage and hence avoiding their toxic side-effects.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Cathepsin B; Cathepsin L; Cathepsins; Cyclophosphamide; Cysteine Endopeptidases; Drug Synergism; Immunologic Factors; Leukemia; Male; Mice; Mice, Inbred DBA; Neoplasm Transplantation

Efficacy of fluconazole (FLCZ), an anti-fungal agent of triazole derivatives, was evaluated in patients with systemic mycoses and suspected mycoses associated with hematologic malignancies including leukemia, myelodysplastic syndrome and malignant lymphoma. Plasma beta-D-glycan levels, the differences between the levels determined toxicolor test and in endospecy test, were also investigated. Fourteen patients with systemic mycoses and 31 patients with suspected mycotic infections were treated with intravenous administration of FLCZ at a daily dose of 400 mg. Excellent to good responses were observed in 4 of the 14 patients (28.6%) with definitive diagnosis of mycosis, and in 18 of the 31 patients (58.1%) with suspected fungal infections, with an overall efficacy rate of 48.9% (22/45). Levels of plasma beta-D-glycan correlated well with efficacies of FLCZ in 19 of 30 patients. In several cases, however, plasma beta-D-glucan levels were low during the entire course of treatment. Even in 10 cases of definite mycosis, 4 cases showed low levels of plasma beta-D-glucan (below 15 pg/ml by repeated determinations). The results indicate that FLCZ is an effective agent for the treatment of severe systemic fungal infections in patients with hematologic disorders. Deep seated mycosis cannot be ruled out even when its plasma levels of beta-D-glucan are low.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Biomarkers; Drug Evaluation; Female; Fluconazole; Glucans; Humans; Leukemia; Lymphoma; Male; Middle Aged; Mycoses

Macrophages obtained from animals treated with beta-1,3-D-glucan-derivatized plastic beads were greatly stimulated, as judged by morphology, esterase release, and cytostatic effect on L-929 tumour cells in vitro. The pretreatment of mice with such beads conferred an apparent absolute local resistance to an otherwise lethal pneumococcal infection but had no effect on the growth of intraperitoneal AA ascites sarcoma. Moreover, peritoneal cells from animals pretreated with glucan beads did not protect the animals in a Winn assay.

Topics: Animals; beta-Glucans; Cell Division; Cell Line; Esterases; Glucans; Leukemia; Macrophage Activation; Macrophages; Melanoma; Mice; Mice, Inbred C57BL; Microspheres; Pneumococcal Infections