galactomannan and Neoplasms

The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a role in carcinogenesis as recognition patterns for galectins. Galectins are members of the lectin family, which show high affinity for β-galactosides. The galectin-glycan conjugate plays a fundamental role in metastasis, angiogenesis, tumor immunity, proliferation and apoptosis. Galectins' action is mediated by a structure containing at least one carbohydrate recognition domain (CRD). The potential prognostic value of galectins has been described in several neoplasms and helps clinicians predict disease outcome and determine therapeutic interventions. Currently, new therapeutic strategies involve the use of inhibitors such as competitive carbohydrates, small non-carbohydrate binding molecules and antibodies. This review outlines our current knowledge regarding the mechanism of action and potential therapy implications of galectins in cancer.

Topics: Calixarenes; Clinical Trials as Topic; Galactose; Galectins; Humans; Mannans; Neoplasms; Pectins; Peptides; Polysaccharides; Thiogalactosides

We systematically reviewed and analyzed the available data for galactomannan (GM), β-D-glucan (BG), and polymerase chain reaction (PCR)-based assays to detect invasive fungal disease (IFD) in patients with pediatric cancer or undergoing hematopoietic stem cell transplantation when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Of 1532 studies screened, 25 studies reported on GM (n = 19), BG (n = 3), and PCR (n = 11). All fungal biomarkers demonstrated highly variable sensitivity, specificity, and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85% to 100% for screening and 70% to 100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of fungal biomarkers in pediatric cancer and HSCT.

Topics: Adolescent; Adult; beta-Glucans; Child; Child, Preschool; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Invasive Fungal Infections; Mannans; Neoplasms; Polymerase Chain Reaction; Young Adult

The objective of this study was to describe the diagnostic yield and complication rate of bronchoalveolar lavage (BAL) and lung biopsy in the evaluation of pulmonary lesions in patients with cancer and recipients of hematopoietic stem-cell transplantation (HSCT).. We conducted a systematic literature review and performed electronic searches of Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were recipients of HSCT, and if they underwent BAL or lung biopsy for the evaluation of pulmonary lesions. Only English language publications were included.. In all, 14,148 studies were screened; 72 studies of BAL and 31 of lung biopsy were included. The proportion of procedures leading to any diagnosis was similar by procedure type (0.53 v 0.54; P = .94) but an infectious diagnosis was more common with BAL compared with lung biopsy (0.49 v 0.34; P < .001). Lung biopsy more commonly led to a noninfectious diagnosis (0.43 v 0.07; P < .001) and was more likely to change how the patient was managed (0.48 v 0.31; P = .002) compared with BAL. However, complications were more common with lung biopsy (0.15 v 0.08; P = .006), and procedure-related mortality was four-fold higher for lung biopsy (0.0078) compared with BAL (0.0018).. BAL may be the preferred diagnostic modality for the evaluation of potentially infectious pulmonary lesions because of lower complication and mortality rates; thus, choice of procedure depends on clinical suspicion of infection. Guidelines to promote consistency in the approach to the evaluation of lung infiltrates may improve clinical care of patients.

Topics: Adult; Aspergillus; Biomarkers; Biopsy; Bronchoalveolar Lavage; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Lung; Lung Diseases; Lung Neoplasms; Mannans; Neoplasms; Pneumonia; Polymerase Chain Reaction; Pulmonary Aspergillosis

Topics: beta-Glucans; Biomarkers; DNA, Fungal; Fungemia; Galactose; Humans; Immunocompromised Host; Mannans; Neoplasms; Sepsis

In the last few years, major advances in the treatment of transplant recipients, with hemato-oncological diseases or admitted to the intensive care unit, has been accompanied by an increase in classical fungal infections and by the emergence of uncommon fungal infections. Despite the development of new diagnostic techniques such as galactomannan detection and the availability of new antifungal agents, these opportunistic infections continue to pose a diagnostic challenge, prolong length of hospital stay, and increase costs. In addition, mortality from these infections is high. The present chapter provides a brief review of the epidemiology of these infections, diagnostic advances, and the new antifungal agents that have been developed in the last few years.

Topics: Anidulafungin; Antifungal Agents; Aspergillosis; beta-Glucans; Candidiasis; Clinical Trials as Topic; Critical Care; Diabetes Complications; Disease Susceptibility; Echinocandins; Fungemia; Galactose; Hematologic Diseases; Humans; Immunocompromised Host; Mannans; Meta-Analysis as Topic; Mycoses; Neoplasms; Opportunistic Infections

Invasive aspergillosis is major cause of morbility and mortality in immunosuppressed patients, in part due to the inability to identify infected patients at an early stage of the disease. Diagnosis is based on a combination of imaging (high-resolution computed tomography) and a number of laboratory techniques including direct examination, culture and circulating markers (galactomannan and Aspergillus DNA) which can be detected at early stages of the infection.

Topics: Antigens, Fungal; Aspergillosis; Aspergillus; Biomarkers; Bone Marrow Transplantation; DNA, Fungal; Enzyme-Linked Immunosorbent Assay; Fungemia; Galactose; Humans; Immunocompromised Host; Mannans; Mycology; Neoplasms; Neutropenia; Polymerase Chain Reaction; Sensitivity and Specificity

Superparamagnetic iron oxide nanoparticles (SPIONs) represent a versatile class of theranostics with profound applications in biomedicine. An eco-friendly modification of SPIONs was attempted with a 110 kDa galactomannan (PSP001) isolated from the fruit rind of Punica granatum. The PSP001 appended SPIONs favor unique advantages including tumor-targeted accumulation and improved biocompatibility. The antineoplastic agent methotrexate (MTX) was covalently attached with the galactomannan in the SPIONs to yield PSP-IO NPs that demonstrated a reduction-sensitive drug release kinetics favoring MTX accumulation selectively in the tumor cells. Folate receptor (FR) targeted cancer cell uptake followed by the stimuli-responsive release of the payload favored improved biocompatibility and lack of toxicity in BALB/c mice. Superior tumor reduction capacity with marked survival benefits was observed in Ehrlich ascites carcinoma (EAC) bearing solid tumor mice. Phantom imaging of the carrier (PSP-IO) and the drug-loaded (PSP-IO-MTX NPs) nano-constructs generated an r2 relaxivity of 335.3 mM

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Folic Acid; Galactose; Humans; Magnetic Iron Oxide Nanoparticles; Magnetic Resonance Imaging; Magnetite Nanoparticles; Mannans; Methotrexate; Mice; Nanoparticles; Neoplasms; Theranostic Nanomedicine

The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sōna

Topics: Aspergillus; Bronchoalveolar Lavage Fluid; Galactose; Humans; Invasive Pulmonary Aspergillosis; Mannans; Neoplasms; Sensitivity and Specificity

Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population.. To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN.. Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds.. A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7 years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P = .99). A difference threshold in sGM Δ ≥ 0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P = .04).. Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN.

Topics: Antifungal Agents; Aspergillosis; Case-Control Studies; Chemotherapy-Induced Febrile Neutropenia; Child; Female; Galactose; Hematologic Neoplasms; Humans; Invasive Fungal Infections; Invasive Pulmonary Aspergillosis; Male; Mannans; Neoplasms

To improve the quality of invasive pulmonary aspergillosis (IPA) management for intensive care unit (ICU) patients using a practical diagnostic scoring model.. This nested case-control study aimed to determine the incidence of IPA in 405 ICU patients, between July 2012 and June 2014, at 6 hospitals in Jakarta, Indonesia. Phenotypic identifications and galactomannan (GM) tests of sera and lung excreta were performed in mycology laboratory, Parasitology Department, Faculty of Medicine, Universitas Indonesia in Jakarta, Indonesia.. The incidence of IPA in the ICUs was 7.7% (31 of 405 patients). A scoring model used for IPA diagnosis showed 4 variables as the most potential risk factors: lung excreta GM index (score 2), solid organ malignancy (score 2), pulmonary tuberculosis (score 2), and systemic corticosteroids (score 1). Patients were included in a high-risk group if their score was greater than 2, and in a low-risk group if their score was less than 2.. This study provides a novel diagnosis scoring model to predict IPA in ICU patients. Using this model, a more rapid diagnosis and treatment of IPA may be possible. The application of the diagnosis scoring should be preceded by specified pre-requisites.

Topics: Adrenal Cortex Hormones; Case-Control Studies; Galactose; Humans; Incidence; Indonesia; Intensive Care Units; Mannans; Middle Aged; Neoplasms; Predictive Value of Tests; Pulmonary Aspergillosis; Risk Factors; Tuberculosis, Pulmonary

Invasive aspergillosis (IA) remains a critical issue in immunosuppressed patients. Detection of galactomannan antigen (GM) in serum samples is included as a criterion of IA by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group. Nevertheless, Aspergillus DNA detection by polymerase chain reaction (PCR) has not yet been included because clinical data validation is lacking. The present study describes the simultaneous performance of GM and PCR tests as routine methods for IA diagnosis.. During the period January 2012 to December 2017, a total of 156 white children hospitalized in a tertiary children's hospital of Athens (97 boys and 59 girls; age range, 5 months-14 years) were examined as possible cases of IA. Patients were classified into 4 groups based on their underlying diseases: hematologic malignancies (107 of 156 [68.6%]), solid tumors (16 of 156 [10.2%]), primary immunodeficiency (12 of 156 [7.7%]), and hereditary immunodeficiency (21 of 156 [13.5%]). GM detection was made with the Platelia Aspergillus Ag kit (Bio-Rad Laboratories, Hercules, California). Sera with a cut-off index ≥0.5 on at least 2 separate blood collections were considered positive. Serum detection of Aspergillus DNA was conducted with real-time PCR MycAssay Aspergillus assay (Myconostica Ltd, Cambridge, United Kingdom). PCR positivity was determined by using a threshold of 38 cycles in at least 1 serum sample. Four or more successive samples per patient were tested.. Overall, 28 of 156 patients (53 of 744 serum samples) were found positive. Eleven patients were positive using both methods (24 samples). Four children were positive only by PCR (6 samples), whereas 13 (23 samples) were positive only with GM in consecutive samples. Agreement of both methods, GM(+)/PCR(+) or GM(-)/PCR(-), was found in 139 patients (90% of total patients) and 715 samples (96.1% of total samples). The agreement of both methods was found: (1) 85% in patients with hematologic malignancies; (2) 100% in patients with solid tumors; (3) 97.5% in patients with primary immunodeficiency; and (4) 98.8% in patients with hereditary immunodeficiency. Overall disagreement was observed in 17 patients, in which the positive result in any of the 2 methods was estimated as true positive in conjunction with radiologic and other clinical findings.. The combination of GM and PCR, provided high diagnostic accuracy in consecutive samples (twice a week). Clinical, radiologic, and other laboratory findings should be taken into consideration in the evaluation of GM and PCR.

Topics: Adolescent; Antigens; Aspergillosis; Aspergillus; Child; Child, Preschool; DNA, Fungal; Female; Galactose; Greece; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Infant; Male; Mannans; Neoplasms; Real-Time Polymerase Chain Reaction

Limited specific data and investigations are available for the diagnosis of Invasive Fungal Infection (IFI) in paediatrics cancer patients. Three non-invasive tests; Platelia Aspergillus EIA for galactomannan (GM), β-D-glucan (BDG) assay and pan-fungal real-time PCR for fungal DNA in blood were evaluated. One hundred twenty-five paediatrics cancer patients at the high risk of IFI were enrolled. Single blood and serum samples were evaluated by all the three methods. Patients were classified into 10 proven, 52 probable and 63 no IFI cases in accordance with EORTC MSG 2008 revised guidelines. The sensitivity, specificity, PPV and NPV of all the three tests in proven, probable and no IFIs cases were analysed singly and in combination. The sensitivity, specificity, PPV and NPV of GM, BDG and pan-fungal real-time PCR were: 87%, 61%, 81%, 69.5% for GM, 88%, 59.5%, 81%, 71.4% for BDG and 89%, 69.2%, 85%, 67.5% for PCR (95% CI). Among different combinations, best combination was found to be GM and PCR with sensitivity, specificity, PPV and NPV of 98.2%, 89.3%, 97.1% and 90% respectively. Single samples must be evaluated by combination of tests.

Topics: Adolescent; Antigens, Fungal; beta-Glucans; Child; Child, Preschool; DNA, Fungal; Fungi; Galactose; Humans; Immunoassay; Infant; Invasive Fungal Infections; Male; Mannans; Neoplasms; Patients; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity

We evaluated the usefulness of a serum Aspergillus PCR assay for the diagnosis and prognosis of invasive aspergillosis in a study involving 941 patients for a total of 5146 serum samples. Fifty-one patients had proven/probable aspergillosis. We compared galactomannan (GM), PCR and mycologic analysis of pulmonary samples in both neutropenic and nonneutropenic patients. PCR performed in serum yielded 66.7% sensitivity, 98.7% specificity, 75.6% positive predictive value and 98.0% negative predictive value, while the GM index yielded 78.4% sensitivity, 87.5% specificity, 27% positive predictive value and 98.6% negative predictive value. The inclusion of PCR in the European Organization for Research and Treatment of Cancer (EORTC) and the Mycosis Study Group (MSG) mycologic criteria permitted the reclassification of nine other cases from possible to probable aspergillosis and increased the sensitivity to 71.7%. Combining the GM index with serum PCR increased the detection rate of invasive aspergillosis with 88.2% sensitivity. PCR was systematically negative in 16 patients with noninvasive forms of aspergillosis (namely aspergilloma and chronic aspergillosis). Remaining PCR positive after a period of 14 to 20 days of treatment was related to poor outcome at 30 and 90 days. Our results also indicate that, unlike the determination of the GM index, the initial fungus load as determined by PCR was highly predictive of 90-day mortality, with the rate of the latter being 15.8% for patients with <150 copies/mL vs. 73.2% for patients at or above that cutoff (p <0.0001). Therefore, PCR appears to be a powerful and interesting tool for the identification of patients with invasive aspergillosis who might benefit from more intense care.

Topics: Adult; Aged; Aged, 80 and over; Aspergillus; Female; Galactose; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Molecular Diagnostic Techniques; Neoplasms; Neutropenia; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; Retrospective Studies; Sensitivity and Specificity; Serum; Young Adult

Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in immunocompromised critically ill patients. New diagnostic strategies for early detection of IPA include the noninvasive biomarkers 1,3-β-d-glucan (BDG), serum, and bronchoalveolar (BAL) fluid galactomannan (GM). The aim of this study was to compare these markers for early detection of IPA in immunosuppressed critically ill patients.. Between December 2014 and December 2015, 49 immunosuppressed patients with respiratory failure were treated at our intensive care unit (ICU). We compared the BDG Fungitell assay with GM Platelia assay in serum and BAL for early detection of IPA. All tests were performed initially after admission at the ICU.. In our study with 49 patients, 13 (26%) had probable IPA. These patients had a higher Acute Physiology And Chronic Health Evaluation II score (28 vs 23, P<.001), Sequential Organ Failure Assessment score (16 vs 14, P<.001), more neutropenia (77% vs 30%, P<.001), worse Horowitz Index (99 vs 73 P<.020), a longer ICU stay (26 vs 17 days, P<.044), and a higher mortality rate (77% vs 58%, P<.001) as compared with patients without probable IPA. The used biomarker BDG presented in patients with probable IPA showed significantly higher levels as compared with patients without probable IPA (375 [103-1000 pg/mL; P<.001] vs 64 [30-105 pg/mL; P < .001]). Comparison of BDG with GM showed that positive serum GM could be detected in only 4 (30%), whereas positive BAL GM could be detected in 12 (92%; mean optical density index, 3.7) of 13 probable IPA cases. These results can be expressed as an overall sensitivity of 88% and a specificity of 82% for probable IPA using the BDG Fungitell assay, a sensitivity of 35% and a specificity of 70% using the serum GM Platelia assay, and a sensitivity of 70% and a specificity of 94% using the BAL GM Platelia assay. The negative predictive values of the used tests were 94% for the BDG Fungitell assay, 94% for the serum GM Platelia assay, and 90% for the BAL GM Platelia assay.. 1,3-β-d-Glucan may be a useful marker for patients under surveillance at risk for IPA. In critically ill patients with immunosuppression, early diagnosis of IPA may be improved by BDG as compared with serum GM. However, diagnostic performance and accuracy increase when BDG is run in parallel with GM from BAL; moreover, the association of the 2 parameters has also the advantage of detecting early and reliable IPA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; APACHE; Aspergillus; Autoimmune Diseases; beta-Glucans; Biomarkers; Bronchoalveolar Lavage Fluid; Critical Illness; Early Diagnosis; Female; Galactose; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Intensive Care Units; Invasive Pulmonary Aspergillosis; Length of Stay; Male; Mannans; Middle Aged; Mortality; Neoplasms; Neutropenia; Organ Dysfunction Scores; Organ Transplantation; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Sensitivity and Specificity; Young Adult

Recent products of piperacillin/tazobactam (PTZ) from the original manufacturer, previously considered a major cause of galactomannan (GM) false-positivity, are reported not to be related to it. However, data regarding generic PTZ are limited and controversial. To evaluate the effect of generic PTZ on GM false-positivity in Korea, we performed a case-control study in adult patients with cancer. A case-control study was designed. Electronic medical records of cancer patients who were admitted and tested for serum GM between March and June 2014 at a tertiary care university hospital were reviewed. During the study period, a single generic PTZ (C manufacturer, Korea) was used. Patients who received PTZ within 24 h prior to serum GM testing were enrolled. Age- and GM test date-matched non-PTZ patients were selected as controls. A total of 110 patients received PTZ within 24 h prior to serum GM testing during the study period. The GM optical density index (ODI) of the PTZ group did not vary significantly from that of the control group (p = 0.251). The percentage of false-positive patients in the PTZ group was also similar to that of the control group (p = 0.538). There was no statistical relationship between GM ODI titer and time interval from PTZ administration (p = 0.095) or cumulative PTZ dose (p = 0.416). In a case-control study that evaluated 220 patients, a generic PTZ in Korea was not related to GM false-positivity.

Topics: Adult; Aged; Anti-Bacterial Agents; Antigens, Fungal; Aspergillosis; Case-Control Studies; False Positive Reactions; Female; Galactose; Humans; Male; Mannans; Middle Aged; Neoplasms; Penicillanic Acid; Piperacillin; Retrospective Studies; Tazobactam; Time Factors

Several galectins are released by tumor cells and macrophages and accumulate in the tumor microenvironment. Galectin-1 and -3 were found to bind to glycosylated receptors at the surface of tumor-infiltrating lymphocytes (TIL), forming glycoprotein-galectin lattices that could reduce the motility and therefore the functionality of surface molecules. In contrast to blood T cells, human TIL show defective IFN-γ secretion upon ex vivo stimulation. We have previously shown that extracellular galectin-3 participates in the impairment of TIL functions. Indeed, disruption of glycoprotein-galectin-3 lattices using anti-galectin-3 antibodies, or N-acetyllactosamine as a competing sugar, boosted cytokine secretion by TIL. Here we have tested a clinical grade galectin antagonist: GM-CT-01, a galactomannan obtained from guar gum reported to be safe in more than 50 patients with cancer.. TIL were isolated from human tumor ascites, treated for 2 to 20 hours with galectin antagonists and tested for function.. We found that GM-CT-01 boosts cytotoxicity of CD8(+) TIL and their IFN-γ secretion in a dose-dependent manner. Treating TIL obtained from patients with various cancers, during a few hours, resulted in an increased IFN-γ secretion in up to 80% of the samples.. These observations pave the way for investigating the potential benefit of this galectin antagonist in patients with cancer, alone or combined with cancer vaccination, in order to correct in vivo impaired functions of TIL.

Topics: Blood Proteins; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytotoxicity, Immunologic; Galactose; Galectin 1; Galectin 3; Galectins; Humans; Interferon-gamma; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Mannans; Neoplasms

We determined the in vitro galactomannan reactivity of isolates recovered from 17 patients with invasive phaeohyphomycosis, 4 of whom had positive galactomannan antigenemia. All isolates were nonreactive using the galactomannan immunoassay. Galactomannan antigenemia in patients with phaeohyphomycosis should raise the possibility of concomitant invasive aspergillosis.

Topics: Aged; Child; Female; Fungi; Galactose; Humans; Immunoassay; Male; Mannans; Middle Aged; Mycoses; Neoplasms

Serum galactomannan (GM) antigen detection is not recommended for defining invasive aspergillosis (IA) in children undergoing aggressive chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT). The ability of the GM test to identify IA in children was retrospectively evaluated in a cohort of children. Test performance was evaluated on samples that were collected during 195 periods at risk of IA. Proven IA was diagnosed in seven periods, all with positive GM test results (true positives, 4%), and possible IA was diagnosed in 15 periods, all with negative GM test results (false negatives, 8%). The test result was positive with negative microbiological, histological and clinical features in three periods (false positives, 1%), and in 170 periods it was negative with negative microbiological, histological and clinical features (true negatives, 87%). The sensitivity was 0.32 and the specificity was 0.98; the positive predictive value was 0.70 and the negative predictive value was 0.92. The efficiency of the test was 0.91, the positive likelihood ratio was 18.3, and the negative likelihood ratio was 1.4. The probability of missing an IA because of a negative test result was 0.03. Test performance proved to be better during at-risk periods following chemotherapy than in periods following allogeneic HSCT. The GM assay is useful for identifying periods of IA in children undergoing aggressive chemotherapy or allogeneic HSCT.

Topics: Adolescent; Aspergillosis; Child; Child, Preschool; Galactose; Humans; Immunoassay; Immunocompromised Host; Infant; Mannans; Mycology; Neoplasms; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Stem Cell Transplantation; Young Adult

Empiric antifungal treatment has become standard of care in children with cancer and prolonged fever and febrile neutropenia (FN), with the downside that it leads to significant over treatment. We characterized epidemiologic, clinical, and laboratory features of invasive fungal disease (IFD) in children with cancer and FN with the aim to identify risk factors for IFD that can aid in better selecting children who require antifungal treatment.. In a prospective, multicenter study, children admitted with FN at high-risk for sepsis, in 6 hospitals in Santiago, Chile were monitored from admission until the end of the FN episode. Monitoring included periodic evaluation of clinical findings, absolute neutrophil count, absolute monocyte count (AMC), serum C-reactive protein (CRP), bacterial cultures, imaging studies, and galactomannan antigen. A diagnosis of proven, probable, and possible IFD was made after episode resolution based on European Organization for Research and Treatment of Cancer classification.. A total of 646 high-risk FN episodes were admitted during the study period, of which 604 were enrolled. IFD was diagnosed in 35 episodes (5.8%) of which 7 (1.2%) were proven, 10 (1.6%) probable, and 18 (3.0%) possible. Four variables obtained on day 4 were significantly more common in IFD cases, which were presence of fever, absolute neutrophil count < or =500/mm, AMC < or =100/mm, and CRP > or =90 mg/L. The combination of fever, AMC < or =100/mm, and CRP > or =90 at day 4 provided a RR for IFD of 5.4 (99% CI, 3.2-9.2) with a sensitivity of 75%, specificity of 87%, positive and negative predictive values of 13% and 99%, respectively.. Fever persisting at day 4 of admission, together with AMC < or =100 and CRP > or =90 significantly increased the risk for IFD in children with cancer.

Topics: Adolescent; Bacteria; C-Reactive Protein; Child; Child, Preschool; Chile; Female; Fever of Unknown Origin; Galactose; Humans; Immunocompromised Host; Infant; Leukocyte Count; Male; Mannans; Mycoses; Neoplasms; Neutropenia; Retrospective Studies; Risk Factors

Invasive aspergillosis (IA) is a serious opportunistic infection in immunocompromised patients. Transplant recipients and patients with cancer represent the highest risk group. The antifungal treatment involves prolonged hospitalization and high economic resources.. to estimate costs represented by IA as an intercurrent complication of oncologic treatment.. Retrospective case-control study. Estimation of the cost of treatment in pediatric oncologic patients with IA in the Hospital Luis Calvo Mackenna during the years 2007-2008 was done. A control for each case of IA paired by sex, age, number of diagnosis and clinical department was selected.. There were 13 patients during the observation period. The attributable cost of treatment of aspergillosis was US $23,600 and the cost for each indicator was: hospital days US $16,500; antifungal therapy US $7,000; and serum galactomannan US $100.. In this study, the cost of treating IA is mainly due to hospitalization and antifungal medications. Three patients acquired IA in spite of staying in a protected environment.

Topics: Adolescent; Antifungal Agents; Antigens, Fungal; Aspergillosis; Case-Control Studies; Child; Chile; Cross Infection; Female; Galactose; Health Care Costs; Humans; Immunocompromised Host; Male; Mannans; Neoplasms; Opportunistic Infections; Retrospective Studies

Topics: Adolescent; Aspergillosis; Female; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Male; Mannans; Neoplasms; Predictive Value of Tests; Transplantation, Homologous

Diagnosing invasive aspergillosis is difficult but might be improved by detection of circulating galactomannan. Although galactomannan antigenemia has been well studied in the detection of invasive aspergillosis in adult patients, little is known about the expression of circulating galactomannan in immunocompromised children with invasive aspergillosis.. We studied the expression of galactomannan antigen by enzyme immunoassay (EIA) in 990 serum samples from 56 pediatric oncology patients (ages 3 months to 18 years) of whom 17 had proven or probable invasive aspergillosis defined by the European Organization for Research and Treatment of Cancer-Mycoses Study Group criteria. Any sample with a galactomannan EIA Galactomannan index value of > or = 0.5 was considered positive.. At least 1 serum sample was positive for 11 of 17 pediatric oncology patients (65.7% sensitivity, 95% confidence interval: 38.3-85.7) with invasive aspergillosis. Galactomannan EIA was positive in 99 of 304 samples from patients with proven or probable invasive aspergillosis, and 7 of 686 (1.0%) samples from 39 control subjects resulted in a positive galactomannan EIA result. At least 1 sample tested positive in 5 of the 39 controls (12.8%, 95% confidence interval: 4.3-27.4). No significant association between accuracy and patient age was observed. Among the 7 evaluable galactomannan-positive patients with IA, the galactomannan EIA produced a positive result before clinical or radiographic evidence of infection in 6 cases, with a lead-time to diagnosis ranging from 1 day to 34 days (median: 10 days). In the remaining case, a positive galactomannan was observed on the same day as diagnosis by non-EIA methods.. The presence of circulating galactomannan is predictive of invasive aspergillosis in most pediatric oncology patients. Galactomannan antigenemia may precede clinical, microbiologic, or radiographic evidence of invasive aspergillosis.

Topics: Adolescent; Antigens, Fungal; Aspergillosis; Child; Child, Preschool; Galactose; Humans; Immunocompromised Host; Immunoenzyme Techniques; Infant; Mannans; Neoplasms; Predictive Value of Tests; Sensitivity and Specificity; Time Factors

Invasive fungal infection (IFI) is a leading cause of infection-related mortality among patients with cancer and prolonged neutropenia and among allogeneic hematopoietic stem cell transplant recipients with graft-versus-host disease. Invasive candidiasis was the principal IFI in the period predating fluconazole prophylaxis, whereas today, invasive aspergillosis and other mold infections cause the majority of deaths from fungal infection in this patient population. The changing epidemiology of IFI, in addition to advances made in antifungal therapeutics and early diagnosis of IFI, warrant a reevaluation of earlier strategies aimed at prevention and early treatment of IFI that were developed several years ago. Here, we propose that persistent neutropenic fever is nonspecific for an IFI and should not be used as the sole criterion for empirical modification in the antifungal regimen in a patient receiving mold-active prophylaxis. We explore the potential benefits and gaps in knowledge associated with employing chest CT scans and laboratory markers as diagnostic adjuncts for IFI. Finally, we discuss the implications of newer antifungal agents and diagnostic adjuncts in the design of future clinical trials to evaluate prophylaxis and early prevention strategies.

Topics: Antifungal Agents; beta-Glucans; Biomarkers; Evaluation Studies as Topic; Fever; Fungi; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Mannans; Mycoses; Neoplasms; Neutropenia; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Tomography, X-Ray Computed; Yeasts

Topics: Aspergillosis; Enzyme-Linked Immunosorbent Assay; False Positive Reactions; Galactose; Humans; Mannans; Neoplasms

Assessing the outcome of patients with invasive pulmonary aspergillosis by using conventional criteria is difficult, particularly when clinical and radiologic worsening coincides with neutrophil recovery. Usually, it is assumed that this deterioration is related to progressive aspergillosis, prompting changes in patient management. However, its temporal relation with neutrophil recovery suggests that it may be caused by an immune reconstitution syndrome (IRIS). Galactomannan is an Aspergillus-specific polysaccharide that is released during aspergillosis and is detected by the serum galactomannan test, which has been approved by the United States Food and Drug Administration for the diagnosis of invasive aspergillosis. In this study, the authors used sequential galactomannan testing to distinguish IRIS responses from progressive aspergillosis.. From April 2001 to December 2006, patients with hematologic malignancies underwent galactomannan screening during periods when they were at risk. The clinical and laboratory findings from patients who had >or=2 consecutive positive galactomannan assays (optical density, >or=0.5) were reviewed.. Nineteen neutropenic patients with aspergillosis developed clinical and radiologic pulmonary deterioration during neutrophil recovery. Deterioration coincided with microbiologic response, as documented by rapid normalization of serum galactomannan, and, in 16 patients, was followed by complete clinical response and survival at 3 months, although there were no changes in antifungal therapy. The 3 patients who died during the first month had no evidence of aspergillosis at autopsy examination.. The authors propose that IRIS was responsible for the current findings and provide a definition for the syndrome. They also recommend serial galactomannan testing to guide aspergillosis management. Declining galactomannan values imply IRIS with an aspergillus response and obviate the need for invasive procedures and alternative antifungal therapies, whereas persistent galactomannan elevation indicates progressive aspergillosis and requires prompt treatment modification.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Aspergillosis; Galactose; Humans; Lung; Lung Diseases, Fungal; Male; Mannans; Middle Aged; Neoplasms; Neutropenia

Early diagnosis of invasive pulmonary aspergillosis (IPA) is important as prompt treatment with antifungal drugs may increase patient survival. Our study investigated the efficiency of routine testing of the Aspergillus galactomannan antigen (AGA) test in combination with chest CT scans for IPA diagnosis.. From February 2002 to June 2004, 74 hemato-oncologic patients undergoing allogeneic stem cell transplantation were prospectively studied with serum AGA twice weekly from admission until death or discharge and weekly afterward when possible. Chest CT scans were performed when fever of unknown origin had lasted beyond 3 days of antibacterial therapy.. Seven patients were classified with possible IPA and two patients, proven IPA. Fourteen patients showed positive results for AGA (OD index>or=1.0 on two subsequent sera). The sensitivity and specificity of the test were 100% and 93%, respectively; the positive and negative predictive values were 64% and 100%, respectively. All patients with possible/proven IPA showed abnormal CT signs; in four cases, imaging signs followed AGA positivity (median 5 days), whereas in five cases they preceded serologic positivity (median, 8 days). In the nine patients with IPA, antifungal therapy was promptly instituted, including lipid formulations of amphotericin B (n=5) or caspofungin (n=4). In only two of the nine patients (22%) with IPA, the primary cause of death was fungal infection.. The combination of AGA detection and early chest CT scans might be considered useful tools to detect minimal changes of IPA. Based on these findings, aggressive antifungal therapy should be initiated.

Topics: Adult; Aged; Antigens, Fungal; Aspergillosis; Aspergillus; Galactose; Hematologic Neoplasms; Humans; Lung Diseases; Mannans; Middle Aged; Neoplasms; Retrospective Studies; Stem Cell Transplantation; Transplantation, Homologous; Treatment Outcome

Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal infection. As the early diagnosis of invasive fungal infection (IFI) is difficult, these infections are still associated with high morbidity and mortality. Recently, Pan-fungal polymerase chain reaction (PCR) has been a promising aid in rapid, early diagnosis of IFI. During the past few years, increasing numbers of suspected IFIs were encountered at our institution in patients with prolonged neutropenia after intensified immunosuppressive chemotherapy. The aim of this study was to investigate the diagnostic utility of both the aspergillus galactomannan (GM) antigen and the pan-fungal PCR assay in the diagnosis of IFI in high risk febrile neutropenic paediatric cancer patients. During one year period, 91 febrile neutropenic (FN) paediatric cases at high risk for developing IFI while receiving chemotherapy were investigated at National Cancer Institute, Egypt. These patients were subjected to clinical evaluation, chest CT scan, conventional blood cultures for bacterial and fungal pathogens, aspergillus GM antigen detection and PCR assay utilizing pan-fungal primers. Of the 91 FN episodes, 15 were proven IFI; whereas 27 cases were either probable (n=13) or possible IFI (n=14), and 49 were unlikely to be IFI episodes. Based on positive results for proven/probable IFI and compared to culture results, Pan-fungal PCR showed sensitivity, specificity, positive and negative predictive values of 75%, 92%, 84% and 87%; respectively. Aspergillus antigen test showed a sensitivity of 79%, specificity of 61%, positive and negative predictive values of 54% and 83%; respectively. A negative PCR in the proven and probable cases was closely related to previous antifungal therapy for a prior history of IFI. In patients at high risk for IFI, neither the sensitivity, nor specificity of the GM test was sufficient. The results of PCR assay was reasonably specific but not very sensitive and had a chance of missing the diagnosis of IFI. The PCR assay seems a promising test for objectively defining IFI, but is not recommended as the only tool for diagnosing IFI. Combining microscopy, culture, and PCR may improve the diagnostic outcome.

Topics: Adolescent; Antigens, Fungal; Aspergillosis; Aspergillus; Blood; Child; Child, Preschool; Egypt; Electrophoresis, Agar Gel; Galactose; Humans; Mannans; Mycoses; Neoplasms; Polymerase Chain Reaction; Predictive Value of Tests; Sensitivity and Specificity; Statistics as Topic

Screening for galactomannan (GM) has been adopted by many European centers as part of the management plan for allogeneic stem cell transplant recipients. However, the temporal onset of GM antigenemia remains unknown. A series of allogeneic stem cell transplant recipients were monitored prospectively, and the relationship between antigenemia and other diagnostic triggers for initiation of antifungal therapy was analyzed. GM detection had a sensitivity of 94.4% and a specificity of 98.8%. Positive and negative predictive values were 94.4% and 98.8%, respectively. This statistical profile was better than that of other triggers, including unexplained fever, new pulmonary infiltrates, isolation of Aspergillus species, and abnormalities seen on computed tomography. Antigenemia preceded diagnosis on the basis of radiologic examination or Aspergillus isolation by 8 and 9 days in 80% and 88.8% of patients, respectively. Antigenemia preceded therapy in 83.3% of patients. Detection of GM was especially useful when patients were receiving steroid treatment or when coexisting conditions masked the diagnosis of invasive aspergillosis. Prospective screening for GM allows earlier diagnosis of aspergillosis than do conventional diagnostic criteria.

Topics: Adolescent; Adult; Age Distribution; Anemia, Aplastic; Aspergillosis; Biomarkers; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Neoplasms; Stem Cell Transplantation; Survival Analysis; Time Factors; Transplantation, Homologous