Serum Galactomannan Assay Research Articles

Diagnostic Accuracy of Serum Galactomannan Assay in Children with Acute Myeloid Leukemia: Effect of the Revised EORTC/MSGERC 2020 Criteria

Diagnostic Accuracy of Serum Galactomannan Assay in Children with Acute Myeloid Leukemia: Effect of the Revised EORTC/MSGERC 2020 Criteria

Prevalence, Risk Factors, Treatment, Outcome, and Diagnosis of COVID-19-Associated Pulmonary Aspergillosis Using a Serum Galactomannan Assay

Background: Coronavirus-associated pulmonary aspergillosis (CAPA) is defined as invasive pulmonary aspergillosis (IPA) occurring in patients with COVID-19 infection. Objectives: This study aimed to identify CAPA patients and describe their clinical-epidemiological characteristics in Ahvaz, Iran, from the third to the fifth COVID-19 waves. Methods: The serum galactomannan (GM) antigen assay was used to detect CAPA in 257 COVID-19 hospitalized patients according to the EORTC/MSGERC (European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium) 2020 criteria. The demographic and clinical data, host risk factors, lung radiographic imaging, laboratory findings, antifungal agents used, and the outcomes of the patients were extracted in cases that were available. All findings were statistically analyzed. Results: Of the 257 patients, 114 (44.35%) were positive for GM levels (CAPA cases). The demographic and clinical information of 51 cases showed that diabetes mellitus (25.5%) was the most common underlying condition, followed by oropharyngeal candidiasis (22%) and hypertension (21.6%). In both surviving and deceased patients, the frequency of CAPA in older ages was statistically significant (r = 0.519; P < 0.0001). In surviving individuals, GM had a significant relationship with age (r = 0.520; P = 0.032), blood glucose (BS; r = 0.497; P = 0.043), diagnosis of hyperglycemia during hospitalization (P = 0.039), and diabetes mellitus (P = 0.039). In deceased patients, the frequency of CAPA in older ages was statistically significant (r = 0.503; P = 0.002). Galactomannan had a significant association with the variables of age (r = 0.503; P = 0.002) and suspicion of fungal infection (P = 0.003). Conclusions: The prevalence of CAPA was high in critically ill patients with COVID-19. Diabetes mellitus, hyperglycemia, and old age are the main factors that predispose COVID-19 patients to IPA.

The Diagnostic Accuracy of Serum Galactomannan Assay in Children with Acute Myeloid Leukemia: Effect of the Revised EORTC/MSGERC 2020 Criteria.

The Diagnostic Accuracy of Serum Galactomannan Assay in Children with Acute Myeloid Leukemia: Effect of the Revised EORTC/MSGERC 2020 Criteria.

The Role of Serum Galactomannan Assay as a Potential Surrogate Biomarker for Fungal Microinvasion in Allergic Fungal Rhinosinusitis.

We conducted this study to determine if serum galactomannan (GM) can be used as a marker to implicate the invasiveness of allergic fungal rhinosinusitis (AFRS), and correlate this value with the aggressiveness of disease documented via computed tomography (CT). All paranasal CT scans done for AFRS patients prospectively over a five-year period (2015-2019) were included. An indigenous 20-point score was used to document the extent of bone erosion seen on CT, wherein a higher score meant a greater extent of bone erosion. It was then correlated with serum GM scores. The median CT scores of galactomannan-positive (GM+) patients were compared with the median CT scores of galactomannan-negative (GM-) patients 3 using Mann-Whitney U test. The patients were divided into five groups based on the extent of disease-No bone erosion, erosion of only sinus wall/orbit, 3 erosion of orbit and skull base, erosion of only skull base and lateral extension of disease into infratemporal fossa (ITF). Subgroup analysis was conducted over mean GM values in these groups using ANOVA test. p-value < 0.05 was considered significant. Statistical analysis was performed using SPSS version 25.0. A total of 92 patients were included (56 males, 36 females). No statistically significant difference was found (p-value = 0.42) between the CT scores of galactomannan-positive (GM+) group and galactomannan-negative (GM-) group. The mean GM scores amongst the five sub-groups did not show a statistically significant difference. Serum galactomannan values correlate poorly with aggressiveness of disease quantified on non-contrast CT of paranasal sinuses.

TUMOR NECROSIS FACTOR (TNF) ALPHA INHIBITORS, ASPERGILLOSIS, AND GALACTOMANNAN: THE PERILS OF BEING MISLED BY AN INSENSITIVE TEST

TUMOR NECROSIS FACTOR (TNF) ALPHA INHIBITORS, ASPERGILLOSIS, AND GALACTOMANNAN: THE PERILS OF BEING MISLED BY AN INSENSITIVE TEST

Differences in Clinical Characteristics of Invasive Tracheobronchial Aspergillosis according to the Presence of Invasive Pulmonary Aspergillosis.

BackgroundThe association of invasive tracheobronchial aspergillosis (ITBA) with invasive pulmonary aspergillosis (IPA) is not well established. We aimed to compare clinical characteristics between patients who exhibited ITBA with IPA and those who exhibited isolated ITBA (iITBA). Additionally, the usefulness of serum or bronchial galactomannan (GM) tests in diagnosing ITBA was evaluated.MethodsThis retrospective single-center case-control study was conducted over a period of 4 years. Fifteen patients were enrolled after confirming the presence of ITBA using bronchoscopy-guided biopsy (iITBA, 7 vs. ITBA+IPA, 8). Clinical characteristics of patients and results obtained from serum or bronchial GM tests were compared between the two groups. Mortality was assessed using data collected from a 6-month follow-up period.ResultsThe ITBA+IPA group showed a higher prevalence of hematologic malignancy (75% vs. 14%, p=0.029), a greater number of patients with multiple bronchial ulcers (75% vs. 14%, p=0.029), lower platelet counts (63,000/μL vs. 229,000/μL, p<0.001), and a mortality rate which was significantly higher (63% vs. 0%, p=0.026) than the iITBA group. In the ITBA+IPA group, 57% of patients tested positive according to the serum GM assay, whereas in the iITBA group, all patients tested negative (p=0.070). The bronchial GM level was high in both groups, but there was no significant difference between them.ConclusionPatients with ITBA+IPA had a greater number of hematologic malignancies with lower platelet counts and a poorer prognosis than patients diagnosed with iITBA. Findings obtained from bronchoscopy and bronchial GM tests were more useful in diagnosing ITBA than the serum GM test results.

Diagnostic yield of a bronchoalveolar lavage fluid galactomannan assay in patients with negative serum galactomannan results suspected to have invasive pulmonary aspergillosis.

There are limited data in real clinical practice on the diagnostic value of a bronchoalveolar lavage (BAL) fluid galactomannan (GM) assay in patients with suspected invasive pulmonary aspergillosis (IPA) who had negative serum GM results. Thus, we investigated the diagnostic performance of a BAL GM assay in patients with negative serum GM assay results who were suspected to have IPA. This retrospective study was performed between May 2008 and April 2019 at a tertiary-care hospital in Seoul, South Korea. All patients with suspected IPA whose serum GM assays revealed negative results who sequentially underwent BAL were enrolled in this study. A total of 341 patients with suspected IPA including four cases of proven IPA, 38 cases of probable IPA, 107 cases of possible IPA and 192 patients without IPA were enrolled. Of these 341 patients, 107 (31%) with possible IPA were excluded from the final analysis. Of 42 patients with proven and probable IPA who had initial negative serum GM results, 24 (57%) had positive BAL GM results (n=24) or BAL fungal culture results (n=8). In addition, BAL revealed evidence of other opportunistic infections including Pneumocystis jirovecii pneumonia (14% [26/190]), cytomegalovirus (CMV) pneumonia (5% [9/188]) and respiratory viral pneumonia (6% [12/193]). Sequential BAL in patients with suspected IPA who had initial negative serum GM results provided additional diagnostic yield in approximately half of patients with evidence of another co-infection.

747. Diagnostic Performance of Bronchoalveolar Lavage Fluid Galactomannan Assay in Patients with Negative Serum Galactomannan Assay Suspected with Invasive Pulmonary Aspergillosis

BackgroundThere are limited data in real clinical practice on the diagnostic value of BAL (bronchoalveolar lavage) fluid galactomannan (GM) assay in patients with suspected invasive pulmonary aspergillosis (IPA) who had negative serum GM results.MethodsThis study was performed at Asan Medical Center, a 2700 bed tertiary-care hospital in Seoul, South Korea between May 2008 and April 2019. All patients with suspected IPA whose serum GM assays revealed negative results and sequentially underwent BAL were enrolled in this study. Patients were classified as proven, probable, possible or not IPA by the revised 2019 EORTC/MSG definition.ResultsA total of 341 patients with suspected IPA including 4 proven IPA, 38 probable IPA, 107 possible IPA, and 192 not IPA were enrolled. Of these 341 patients, 107 (31%) with possible IPA were excluded from the final analysis. Of 42 patients with proven or probable IPA who had initial negative serum GM results, 24 (57%) revealed positive BAL GM results (n=24) or BAL fungal culture (n=8). Among the remaining 18 (43%), 2 (5%) were diagnosed as proven IPA by the histopathologic exam from transbronchial lung biopsy, 6 (14%) as probable IPA by subsequent sputum fungal culture, and 10 (24%) as probable IPA by repeated serum GM assay after BAL. Of 192 patients with not IPA, 14 (7%) revealed positive BAL GM results (n=14) or BAL fungal culture (n=8). The diagnostic performance of various tests is shown in Table 1.Table 1. Diagnostic performance of various diagnostic tests in patients with suspected IPA who had negative serum GM results ConclusionSequential BAL in patients with suspected IPA who had initial negative serum GM results provided additional diagnostic yield in about half of patients.Disclosures All Authors: No reported disclosures

908P Impact of serum galactomannan assay on diagnosis and outcome of invasive fungal infections in high risk febrile neutropenia: A prospective cohort study

908P Impact of serum galactomannan assay on diagnosis and outcome of invasive fungal infections in high risk febrile neutropenia: A prospective cohort study

Serum galactomannan level for the diagnosis of invasive pulmonary aspergillosis in hospitalized patients with chronic obstructive pulmonary disease (COPD): Meta-analysis

Background: The serum galactomannan (GM) assay is used to diagnose invasive pulmonary aspergillosis (IPA). We conducted a meta-analysis to assess the overall accuracy of the serum GM test for detecting IPA in critically ill COPD patients. Methods: The web of science, Pubmed, Embase, China National Knowledge Infrastructure, WanFang, Weipu (VIP) Science China databases were searched for all the eligible studies, including randomized controlled trials and prospective studies up to February 2019. We selected and assessed articles that reported diagnostic data related to serum GM for diagnosis of invasive fungal disease in hospitalized COPD patients. Additionally, pooled sensitivity (SEN), specificity (SPE), true positive (TP), false positive (FP), true negative (TN), false negative (FN) were estimated for summarizing overall test performance. Results: Of 1104 articles screened, 14 studies were involved in the meta-analysis with 1127 patients in the COPD serum sample. The pooled serum GM assay results with cutoff value of 0.5 were as follows: DOR: 15 (95% CI, 6–38), sensitivity: 0.57 (95% CI, 0.37–0.75), specificity: 0.92 (95%,CI, 0.85–0.96), and the SROC was 0.89 (95% CI, 0.86–0.91). When the cutoff value was 1, the results were as follows: DOR: 33 (95% CI, 15–70), sensitivity: 0.57 (95% CI, 0.39–0.73), specificity: 0.96 (95% CI, 0.93–0.98), and SROC was 0.95 (95% CI, 0.92–0.96). Conclusion: Serum GM can be used to assist in diagnosis of IPA in critically ill COPD patients. When cutoff value was set as 1, serum GM had better diagnostic value compared to those with cutoff of 0.5.

The utility of bronchoalveolar lavage fluid and serum galactomannan assay in patients with nonresolving pneumonia in a tertiary care hospital

Background The fungus aspergillus causes a plethora of diseases in humans. Invasive pulmonary aspergillosis (IPA), a serious opportunistic infection seen in immunosuppressed or hospitalized patients with severe underlying diseases, is associated with high rates of morbidity and mortality. The diagnosis of IPA is a challenge in general hospital population. This study was undertaken to evaluate the utility of galactomannan (GM) assay in bronchoalveolar lavage (BAL) fluid and serum for the diagnosis of IPA in patients with nonresolving pneumonia in a tertiary care hospital. Patients and methods Patients with nonresolving pneumonia for whom both BAL and serum GM assays, along with BAL culture for fungus, were evaluated from January 2016 to June 2017. Results A total of 64 patients had the tests done in the study period. All the patients had more than one associated underlying risk factor. Diabetes was seen in 35 (64.68%) patients and steroid intake in 34 (53.12%). Aspergillus flavus was the most common fungus cultured. Moreover, 14 of the culture positives had a serum GM level of more than 0.5 GM index, and all culture positives had BAL GM level of more than 0.5 GM index. Receiver operating characteristic curves revealed a cutoff of 0.91 for serum GM, which provides sensitivity of 66% and specificity of 63% and 1.01 for BAL GM, with a sensitivity of 88% and specificity as of 78%. The all-cause mortality of 78.8% was noted with both BAL and BAL GM positive (P=0.001). Conclusion A combination of clinical, radiological, culture, and GM assay of both BAL and serum would help in the diagnosis of IPA in hospitalized patients with nonresolving pneumonia.

How to make a fast diagnosis in invasive aspergillosis.

Aspergillosis is more common among immunocompromised patients with neutropenia or immunosuppression due to corticosteroid use, and infections are typically of the lung or sinuses. For diagnosis, broncholaveolar lavages (BALs) and lung biopsies are the specimens of choice. Culture and microscopic examinations are a must have and laboratory results should immediately be reported to the clinic. Fungal elements (hyphae) display the proof of an infection if present in primarily steril specimens, independent of culture results. Microscopy should be performed preferably using optical brighteners and histopathology using Gomori's methenamine silver stain or Periodic acid-Schiff. Serum and BAL galactomannan assays are recommended as markers for the diagnosis of invasive aspergillosis, PCR should be considered in conjunction with other diagnostic tests. Antifungal treatment decreases GM sensitivity. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates.

Clinical features and cause analysis of false positive results of Aspergillus galactomannan assay in pulmonary cryptococcosis patients.

There have been conflicting reports of false positive galactomannan assay results in patients with systemic cryptococcosis. We sought to determine the frequency of GM positivity in patients with pulmonary cryptococcosis and confirm the source of this cross-reactivity in vitro. We conducted a retrospective study to elucidate the rate of galactomannan (GM) false positivity and cause in a cohort of 29 patients with pulmonary cryptococcal disease. The production of GM cross-reacting substances by clinical isolates and laboratory isolates of C. neoformans was tested in vitro. The mean serum GM index (Platelia Aspergillus) in patients with pulmonary cryptococcosis was 1.06, with 16 (55.2%) of patients having values above the positive cutoff value of 0.5. GM index values significantly decreased after treatment of cryptococcosis. There was no significant correlation between galactomannan and cryptococcal glucuronoxylomannan antigen (Eiken Latex test) results. Culture supernatants from clinical isolates and wild-type C. neoformans did not react in the GM assay; however, growth in the presence of 6% sodium chloride induced the production of cross-reacting GM antigens in culture supernatants from clinical isolates, wild type and a glucuronoxylomannan-deficient mutant of C. neoformans, but not in culture supernatants from a galactoxylomannan-deficient strain. Our results support the cross-reactivity of cryptococcal galactoxylomannan with the serum GM assay in vitro and in patients with pulmonary cryptococcal infection.

Prevalence of pulmonary aspergillosis among chronic obstructive pulmonary disease patients presented with acute exacerbation

Introduction Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a major event through the life of all chronic obstructive pulmonary disease (COPD) patients. This study was designed to assess the prevalence of pulmonary aspergillosis among COPD patients presented with acute exacerbation. Patients and methods A cross-sectional study was withheld and recruited 20 patients diagnosed with AECOPD who were admitted in the respiratory care unit (RCU). Sociodemographic data were recorded. All patients had undergone chest radiography together with serum galactomannan (GM) assay in order to detect pulmonary aspergillosis. Results Twenty patients diagnosed with AECOPD were admitted to the RCU, among which 30% of them died along their course of RCU stay. Of these patients, one-third was found to have pulmonary aspergillosis using serum GM. Serum GM showed no difference among patients who died compared with survived subjects; however, it was significantly higher among patients diagnosed with pulmonary aspergillosis. Using steroids in the past 3 months was not a risk factor for positive aspergillosis, whereas patients with the increased number of exacerbations showed an increased risk for aspergillosis. Conclusion Pulmonary aspergillosis is considered as one of the risk factors of AECOPD being detected among 20% of all studied patients. Frequent exacerbations are associated with pulmonary aspergillosis among COPD patients. Serum GM antigen is used as a marker of positive aspergillosis; however, it did not differ much among the patients who died; therefore, it could not be used as a marker of mortality among AECOPD patients.

Breakthrough invasive aspergillosis and diagnostic accuracy of serum galactomannan enzyme immune assay during acute myeloid leukemia induction chemotherapy with posaconazole prophylaxis.

Posaconazole prophylaxis has demonstrated efficacy in the prevention of invasive aspergillosis during prolonged neutropenia following acute myeloid leukemia induction chemotherapy. Antifungal treatment decreases serum galactomannan enzyme immunoassay diagnostic accuracy that could delay the diagnosis and treatment.We retrospectively studied patients with acute myeloid leukemia who underwent intensive chemotherapy and antifungal prophylaxis by posaconazole oral suspension. Clinical, radiological, microbiological features and treatment response of patients with invasive aspergillosis that occurred despite posaconazole prophylaxis were analyzed. Diagnostic accuracy of serum galactomannan assay according to posaconazole plasma concentrations has been performed.A total of 288 patients with acute myeloid leukemia, treated by induction chemotherapy, who received posaconazole prophylaxis for more than five days were included in the present study. The incidence of invasive aspergillosis was 8% with 12 (4.2%), 8 (2.8%) and 3 (1%), possible, probable and proven invasive aspergillosis, respectively. Posaconazole plasma concentration was available for 258 patients. Median duration of posaconazole treatment was 17 days, and median posaconazole plasma concentration was 0.5 mg/L. None of patients with invasive aspergillosis and posaconazole concentration ≥ 0.5 mg/L had a serum galactomannan positive test. Sensitivity of serum galactomannan assay to detect probable and proven invasive aspergillosis was 81.8%. Decreasing the cut-off value for serum galactomannan optical density index from 0.5 to 0.3 increased sensitivity to 90.9%.In a homogenous cohort of acute myeloid leukemia patients during induction chemotherapy, increasing the posaconazole concentration decreases the sensitivity of serum galactomannan assay.

Utility of a serum Aspergillusgalactomannan assay in diagnosis of invasive pulmonary Aspergillosis in HIV/AIDS patients: a prospective analysis

Background: Invasive pulmonary aspergillosis (IPA) is a life threatening infection among immunocompromised patients. A timely and precise diagnosis of this condition is often precluded by lack of sensitive and specific noninvasive diagnostic tools. Detection of galactomannan has emerged as a promising tool in this regard. While the analytical performance of serum galactomannan assay has been extensively evaluated in various high risk groups, its possible utility in HIV/AIDS patients is yet to be explored. The present study was undertaken to evaluate the yield of a serum galactomannan assay for diagnosis of IPA in a cohort of HIV/AIDS patients.Methods: 49 febrile HIV reactive patients with co-existent symptomatic AIDS were prospectively enrolled for the evaluation. Blood samples were drawn from each patient and serum galactomannan screening was performed employing the commercially available serum galactomannan assay, Platelia™ Aspergillus EIA. An optical density index >0.5 for at least two serum samples was considered the defining criteria for a positive result. Furthermore, sputum samples were collected and direct microscopic examination (10% potassium hydroxide wet mount) and fungal cultures were performed.Result: In accordance with the definitions laid down under EORTC/MSG (European Organization for Research and Treatment of Cancer / Mycoses Study Group) criteria, ten cases of probable and 23 cases of possible IPA were diagnosed. The sensitivity, specificity, and positive and negative predictive values of Platelia™ Aspergillus EIA for patients with probable IPA were 90%, 100%, 100% and 94.12 % respectively.Conclusion: Serum galactomannan assay has a high sensitivity and specificity and when complemented with relevant lower respiratory tract symptomatology and imaging findings, can serve as a useful adjunct to conventional modalities for the diagnosis of IPA in HIV/AIDS patients. DOI: 10.21276/APALM.1439

Cytomegalovirus pneumonia coexisting invasive pulmonary aspergillosis in an old aged diabetic patient after prolonged intensive care

Introduction Cytomegalovirus (CMV) pneumonia is an important cause of morbidity and mortality in transplant recipients, hematological malignancies on chemotherapy, and HIV-infected patients. Invasive pulmonary aspergillosis (IAP) occurs primarily in patients with severe immunodeficiency. Both infections have dramatically increased in the patients with impaired immune state associated with critically ill patients and those with chronic obstructive pulmonary disease. Case description The 93-year-old diabetic woman was admitted to the intensive care unit (ICU) due to urosepsis. Antibiotic therapy with piperacillin-tazobactam was given. As clinical progression to profound shock and multiple organ failure, high-dose vasopressors, hydrocortisone and fluid resuscitation were given. After short course of continuous venovenous hemofiltration was used, the hyperkalemia and metabolic acidosis were improved. The patient was maintained on regular haemodialysis. However, active gastric and duodenal ulcers with bleeding were identified by endoscopy. Hemostasis and high-dose pantoprazole infusion were given. As stable condition after ICU stay for one month, she was transferred to respiratory care center for weaning ventilator. However, CXR showed partial consolidation over bilateral lung, favoring inflammatory process. The sputum culture showed Acinetobacter baumannii and Aspergillus species. Meanwhile, the results of CMV-PCR for serum and sputum samples were positive. Blood CMV virus load was 8140IU/mL. In spite of one week therapy with imipenem and ganciclovir, the sepsis and pneumonia did not improve. The CXR still showed severe pulmonary edema and high airway pressure was noted. The serum Aspergillus galactomannan (GM) antigen revealed >5.59 index (normal, Conclusion Early diagnosis and treatment of CMV infection is important in view of the poor prognosis of established infection. Strategies include pre-emptive therapy when viral load increases or CMV-PCR becomes positive on serial monitoring. As cultures for Aspergillus spp are positive only in few cases, serum GM assay is useful for early diagnosis of IPA even before the clinical symptoms and signs becoming obvious. Old age, diabetes, hemodialysis, steroid use and prolonged ICU stay might predispose our patient to develop IPA and CMV pneumonia. Voriconazole was not given for our patient in time, which also highlighted the importance of early diagnosis and therapy.

The misleading effect of serum galactomannan testing in high-risk haematology patients receiving prophylaxis with micafungin

ObjectivesTo investigate the performance of the routine serum galactomannan (sGM) assay in the diagnosis of invasive aspergillosis (IA) in high-risk haematology patients receiving prophylaxis with micafungin. MethodsRetrospective study including all haematological patients who received prophylaxis with micafungin during high-risk IA episodes (neutropenic patients after chemotherapy for acute myeloid leukaemia/myelodysplastic syndrome; allogeneic haematopoietic stem-cell transplantation during early neutropenic phase or graft-versus-host disease requiring high prednisone doses) and for whom at least one sGM result was available. Episodes were classified as follows: true-positive (positive GM in the context of IA), false-positive (positive GM result in patients who had no evidence of IA), true-negative (negative GM test results and no IA), or false-negative (negative GM test in the context of IA). Non-evaluable patients were excluded. ResultsAmong 146 evaluable episodes, four were true-positive in the context of probable breakthrough IA (incidence of breakthrough IA, 2.7%); 111/146 high-risk episodes (76%) were considered true-negative and 31/146 (21.2%) were considered false-positive. No false-negative episodes were detected. All but one of the false-positive episodes were detected in surveillance GM tests, leading to high-resolution CT scans in eight cases (8/31; 25.8%), all of which were negative. The positive predictive and negative predictive values of sGM for surveillance and diagnostic approaches were 3.2% (1/31) and 100% (110/110) and 75% (3/4) and 100% (1/1), respectively. ConclusionsSurveillance of asymptomatic patients receiving prophylaxis with micafungin using sGM is unnecessary, because the results are either negative or false-positive. However, sGM remains useful in the diagnosis of breakthrough IA in symptomatic patients during prophylaxis.

Validation of single nucleotide polymorphisms in invasive aspergillosis following hematopoietic cell transplantation

AbstractInvasive aspergillosis (IA) is a significant cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Previous studies have reported an association between IA development and single nucleotide polymorphisms (SNPs), but many SNPs have not been replicated in a separate cohort. The presence of a positive serum galactomannan assay (SGM+) has also been associated with a worse prognosis in patients with IA, and genetic determinants in this subset of patients have not been systematically studied. The study cohort included 2609 HCT recipients and their donor pairs: 483 with proven/probable IA (183 SGM+) and 2126 with no IA by standard criteria. Of 25 SNPs previously published, we analyzed 20 in 14 genes that passed quality control. Samples were genotyped via microarray, and SNPs that could not be genotyped were imputed. The primary aim was to replicate SNPs associated with proven/probable IA at 2 years; secondary goals were to explore the associations using an end point of SGM+ IA or proven/probable IA using a different genetic model or time to IA (3 months vs 2 years) compared with the original study. Two SNPs in 2 genes (PTX3, CLEC7a) were replicated. Thirteen SNPs in 9 genes had an association at P ≤ .05 using the secondary aims (PTX3, CLEC7a, CD209, CXCL10, TLR6, S100B, IFNG, PLG, TNFR1), with hazard ratios ranging from 1.2 to 3.29. Underlying genetic differences can influence development of IA following HCT. Identification of genetic predispositions to IA could have important implications in donor screening, risk stratification of recipients, monitoring, and prophylaxis.

The limited role of serum galactomannan assay in screening for invasive pulmonary aspergillosis in allogeneic stem cell transplantation recipients on micafungin prophylaxis: a retrospective study.

BackgroundWe evaluated the outcomes of serum galactomannan (GM) assay for the screening of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients while on primary antifungal prophylaxis (PAP).MethodsThis study included patients with hematologic disorders who underwent alloHSCT from January 2013 to November 2015. Patients received routine PAP with fluconazole before 2014 and micafungin after 2014; serum GM tests were performed and retrospectively analyzed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum GM tests for detection of probable/proven IPA were evaluated. The serial change of serum GM levels was illustrated on a time series plot.ResultsA total of 136 alloHSCT recipients at Seoul National University Hospital were included in the study. Fluconazole was administered in 72 patients for PAP, while micafungin was administered in the remaining 64 patients. The overall sensitivity, specificity, and NPV of serum GM assays were 95.8% (95% confidence interval [CI] 78.9–99.9%), 93.8% (95% CI 91.7–95.5%), and 99.8% (95% CI 99.1–100.0%), respectively. However, the PPV of GM tests was relatively low at 35.4% (95% CI 23.9–48.2%). The serial change in serum GM levels differed according to the antifungal agents used. With effective PAP using micafungin, serial serum GM levels showed zero order kinetics during the neutropenic period.ConclusionAlthough the serum GM assay is a sensitive and specific test for detecting IPA in alloHSCT recipients, its role for routine surveillance in an era of effective PAP with micafungin is limited.