High incidence of false-positive Aspergillus galactomannan test in multiple myeloma

American Journal of Hematology (Impact Factor: 3.8). 01/2010; 85(6):449-51. DOI: 10.1002/ajh.21697
Source: PubMed

ABSTRACT Invasive aspergillosis (IA) remains one of the most significant causes of morbidity and mortality in patients with hematological malignancies undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT), mainly due to the difficulty in its early diagnosis. Monitoring of galactomannan (GM) antigen, an exoantigen of Aspergillus, in the blood by sandwich ELISA is a useful and noninvasive method for early diagnosis of IA. The GM test has a sensitivity of 67-100% with a specificity of 81-99% in neutropenic patients and allogeneic transplant recipients [1-3]. Although it has been widely used as a diagnostic criterion for IA [4,5], one of the major limitations of this assay is false-positivity, particularly in pediatric patients [1], patients with graft-versus-host disease (GVHD) [6,7], and those taking dietary GM [8,9] or fungus-derived antibiotics, such as piperacillin-tazobactam (PIPC/TAZ) [10-12].

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Available from: Yasuo Mori, Apr 15, 2014
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    • "In contrast to one report of high false-positivity rate in multiple myeloma,[17] in our study only one out of 20 myeloma patients (undergoing auto-HSCT) had two false-positive values. However, though this patient did not have clinical signs of IA and chest radiograph was normal on more than one occasion, he did have fever >96 h on antibiotics and received AmB for 9 days. "
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    ABSTRACT: Invasive aspergillosis (IA) is a leading cause of mortality in acute leukemia and hematopoietic stem cell transplantation (HSCT). To determine the yield of galactomannan (GM) assay for the diagnosis of probable IA, its temporal relationship with the computed tomography (CT) scans and correlation with mortality in AL and HSCT. Consecutive neutropenic episodes (n=150) among inpatients aged ≥15 years with AL or recipients of HSCT were prospectively evaluated over 1½ years. All patients underwent weekly serum GM assay and optical density index >0.5 for ≥2 samples was defined as positive. IA was diagnosed according to EORTC 2008 guidelines. Of the 150 episodes enrolled, 43 (28.7%) were diagnosed with IA: possible 25 (16.7%), probable 17 (11.3%) and proven 1 (0.7%). The yield of GM assay in diagnosing probable IA was 17/42 (40.5%). In 88.2% of probable IA episodes, GM was positive before high-resolution CT at a median of 10 days (range 1-16). In the episodes with ≥2 samples tested, fatality was higher in those ≥2 values positive for GM, compared to the rest (31% vs. 13.2%, odd ratio 2.96, 95% CI 1.09-8.00; P=0.04). In AL and HSCT, GM assay could identify patients with probable IA earlier than CT chest and also predicted a higher risk of death.
    Indian journal of medical and paediatric oncology 04/2013; 34(2):74-9. DOI:10.4103/0971-5851.116181
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    ABSTRACT: Prompt diagnosis of infection in febrile neutropenia hosts with hematological malignancy is essential in directing therapy. We highlight experience using modern molecular and biomarker-based methods to diagnose bacterial and fungal bloodstream infections and invasive aspergillosis in these patients. Nucleic acid amplification-based strategies are used to detect and identify pathogens from blood cultures or from blood/clinical specimens; the latter are more likely to influence clinical management. Advances in DNA extraction include standardization of isolation of Aspergillus DNA from blood. Broad-range and/or multiplex PCR generally have greater clinical utility than pathogen-specific assays. However, Aspergillus-PCR assays are useful in confirming/excluding disease and monitoring high-risk patients for invasive aspergillosis. Commercial real-time PCR/peptide nucleic acid fluorescent in-situ hybridization systems, used as adjuncts to blood cultures, to detect bacteria and fungi in blood cultures (or blood), are as sensitive as culture and enable earlier institution of targeted therapy. Yet there are no data indicating that molecular detection of bacterial/fungal pathogens influences patient outcomes. Positive serum Aspergillus galactomannan and 1,3-β-D-glucan tests are useful biomarkers in the diagnosis/screening of fungal infection, and have potential as measures of response to antifungal therapy. Serum procalcitonin levels can help differentiate infectious, from noninfectious, fever. Combined molecular and nonmolecular testing likely offers optimal diagnostic accuracy. Numerous PCR-based and biomarker tools are available for the diagnosis and screening of infection in febrile neutropenia hosts. The optimal approach remains to be resolved by prospective studies examining the impact of one or more of tests on patient outcomes.
    Current Opinion in Infectious Diseases 12/2010; 23(6):567-77. DOI:10.1097/QCO.0b013e32833ef7d1 · 5.01 Impact Factor
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    ABSTRACT: Although invasive fungal infections (IFIs) are relatively rare, they are important causes of morbidity and mortality in immunocompromised pediatric patients. Early and precise diagnosis of IFI is important to allow antifungal treatment to be started in time and to reduce the unnecessary use of toxic antifungal agents. Although traditional approaches such as direct microscopic examination, histopathological evaluation and cultivation are still gold standard, the diagnosis of IFI is generally difficult because of inadequate sensitivity and specificity with these tests. Commercial systems detecting the Aspergillus cell wall antigen galactomannan and 1,3-β-D-glucan are seen as the most convenient nonculture methods for the diagnosis of the IFI and monitoring of antifungal treatment. Several molecular methods have been described for the diagnosis of opportunistic mycoses. However, they have not been standardized and have only been used in experimental studies.
    Expert Review of Anti-infective Therapy 03/2011; 9(3):289-98. DOI:10.1586/eri.10.168 · 3.46 Impact Factor
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