Serum Galactomannan Research Articles

Therapeutic Granulocyte Transfusions in Neutropenic Patients with Invasive Pulmonary Aspergillosis,

Abstract 3372 Background:Granulocyte transfusions (GTX) are used as an additional therapeutic option in patients with severe neutropenia following chemotherapy constituting an increased risk for life-threatening bacterial and fungal infections. We hypothesized that interventional GTX would provide a clinical benefit for neutropenic patients with invasive pulmonary aspergillosis (IPA). Methods: We reviewed the clinical outcome of 44 patients with severe neutropenia (46 cases) and underlying hematological malignancies suffering from IPA unresponsive to standard antifungal therapy. They received a total of 181 human recombinant granulocyte colony-stimulating factor (rh G-CSF) stimulated GTX at Freiburg University medical center from 1996 – 2009. Neutropenias were caused by conventional chemotherapy (n=38), conditioning chemotherapy for allogeneic (n=4) and autologous (n=2) hematopoietic cell transplantation (HCT), aplastic anemia (n=1) and by intense immunosuppressive (n=1). Donors were exclusively relatives and acquaintances of the recipients. IPA was diagnosed by clinic, computed tomography (CT) scan, serological or microbiological measures. Response of GTX was evaluated by repeated CT, decreasing C-reactive protein (CRP) levels, hematopoietic regeneration and clearance of serum galactomannan antigen. Results: A median of 3 GTX (range 1–25) containing a median total of 59.4×109 (range 3–170) white blood cells per GTX were administered. All but five (3%) transfusions were well tolerated. Median duration of neutropenia proceeding GTX was 15.5 d (range 4–70). Resolution of infection or clinical improvement was achieved in 29 (63%) patients with IPA and haematopoietic recovery has been assumed within 10 days after the last GTX in 34 patients (74%). Thirty-three (72%) patients were alive one month after the first GTX. Overall, progressive malignant disease was the main cause of death. Patients not responding to GTX died without on septic complications despite appropriate antibacterial and antifungal treatment. Nine out of 26 neutropenic patients receiving GTX after conventional chemotherapy underwent allogeneic HCT later on after control of IPA. Conclusions: Rh G-CSF stimulated GTX are a safe and effective therapeutic tool for patients with hematological malignancies suffering from profound neutropenia and antifungal-therapy resistant IPA. GTX may serve as a bridging therapy in severe neutropenic patients with IPA scheduled for allo-HCT. Disclosures:Bertz:GILEAD: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees.

Serum Galactomannan Useful for Evaluating Response in Invasive Aspergillosis

Invasive aspergillosis (IA) is a leading cause of morbidity and mortality in immunocompromised patients. The European Organization for Research and

Galactomannan Antigenemia after Infusion of Gluconate-Containing Plasma-Lyte

We demonstrated that sodium gluconate was the factor causing false-positive galactomannan (GM) antigenemia of Plasma-Lyte hydration solution. Infusion of sodium gluconate-containing solution but not gluconate-free Plasma-Lyte resulted in positive serum GM antigenemia. Serum GM concentrations also correlated with the volume and in vitro concentrations of GM within gluconate-containing solutions of infused Plasma-Lyte.

Utility of serum galactomannan in diagnosis and treatment of invasive fungal infection patients

Objective To evaluate the value of serum galactomannan platelia aspergillus kit in the diagnosis and treatment of invasive fungal infection(IFI) patients. Methods A total of 178 serum samples from 74 high risk patients were collected. ELISA assay was used to detect the level of GM antigen. Refer to domestic IFI diagnostic criteria, 16 patients include the proven cases and probable cases were defined as study group, while 29 patients of improbable cases defined as control group. Fourflod table was founded,by which the sensitivity,specificity,positive predictive value, negative predictive value of this GM test were calculated. Meanwhile, a total of 53 patients received antifungal therapy which divided into GM-positive group(21 patients with I≥0. 5) and GM-negative group(32 patients with I ＜0. 5). The therapeutic effect comparison of two groups was made according to curative effect criterion. Results According to the certainty level of IFI diagnosis, 1,9,10 and 4 patients were identified as GM positive in proven, probable,possible and improbable IFI groups respectively. The prevalence of GM in these 4 groups was 50％ ,64％ ,34％ and 14％ ,respectively. The sensitivity and specificity of galactomannan ELISA assay were 63％ ,86％ respectively. The positive and negative predictive values were 71％ and 81％ respectively. The diagnose accordance rate was 78％, the Younden index was 0. 49. The efficacy of fluconazole in GM-positive patients was significant lower than in GMnegative patients( x2 =4. 95 ,P ＜0. 05) ,while The efficacy of non-fluconazole drug was superior to that in GM-negative patients( x2 =4. 88,P ＜ 0. 05). After antifungal therapy, the GM value of GM-positive patients decreased significantly( t =2. 13 ,P ＜0. 05). Conclusion The galactomannan ELISA assay with high specificity, could be helpful in diagnosis and choicing effective anti-fungi drug in clinic. Key words: Galactomannan; Mycology

ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients

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.

Computed tomography findings in invasive pulmonary aspergillosis in non-neutropenic transplant recipients and neutropenic patients, and their prognostic value

We evaluated CT findings and their prognostic value in non-neutropenic transplant recipients with invasive pulmonary aspergillosis (IPA) compared with neutropenic patients with IPA. All adult patients during a 27-month who met the criteria for proven or probable IPA according to the 2008 EORTC/MSG criteria were retrospectively enrolled. Initial CT findings were reviewed by two radiologists blinded to the patients' demographics and clinical outcomes. A total of 50 non-neutropenic transplant recipients and 60 neutropenic patients were enrolled. Consolidation-or-mass, halo signs, and angio-invasive form were observed less often in non-neutropenic transplant recipients than in neutropenic patients: (56%, 26%, and 32%) versus (78%, 55%, and 60%, p = 0.01, p = 0.002, and p = 0.003, respectively). Multivariate analysis revealed that macronodules (HR 0.31, p = 0.001), multiple infarct-shaped consolidations (HR 4.26, p < 0.001), renal replacement therapy (HR 5.62, p < 0.001) and persistence of a positive serum galactomannan (HR 7.14, p < 0.001) were independently associated with 90-day mortality. Our data indicate that CT findings in non-neutropenic transplant recipients with IPA are similar to those in neutropenic patients with IPA except that consolidation-or-mass, halo sings, and angio-invasive form are less frequent, and certain CT findings such as macronodules and multiple infarct-shaped consolidations have prognostic implications in IPA.

A prospective comparison of galactomannan in bronchoalveolar lavage fluid for the diagnosis of pulmonary invasive aspergillosis in medical patients under intensive care: comparison with the diagnostic performance of galactomannan and of (1→ 3) – β – d-glucan chromogenic assay in serum samples

Diagnosis of fungal pneumonia (FP) in critically ill patients is challenging. Circulating biomarkers for the diagnosis of FP have limitations and the combination of different assays in serum samples and directly from the target organ may further improve the diagnosis of FP. We prospectively assessed the diagnostic utility of paired galactomannan (GM) in bronchoalveolar lavage fluid (BAL) and serum GM and (1→3)–β–d-glucan (BG) assays in critically ill patients at risk of FP. Patients with FP were classified according to European Organisation for Research and Treatment of Cancer-Mycoses Study Group criteria, with modifications. Out of 847 admissions, 51 patients were eligible. There were nine invasive aspergillosis (IA) cases (four proven, five probable), three proven Pneumocysitis jirovecii pneumonia (PJP) cases and one mixed FP case (probable IA and proven PJP). The diagnostic accuracy as given by the area under the receiver operating characteristic curve in IA cases (proven and probable) for GM in BAL was 0.98 (95% CI, 0.94–1.00), whilst for GM and BG in serum it was 0.85 (95% CI, 0.74–0.96) and 0.815 (95% CI, 0.66–0.96), respectively. For IA cases (proven and probable) AUC for GM in BAL was significantly higher than GM and BG in serum (p 0.025 and p 0.032, respectively). In one of four proven and one of six probable IA cases, GM in serum remained negative, whereas GM in BAL was positive. In patients with IA, GM (90%) and BG (80%) appeared a mean of 4.3 days (range, 1–10 days) before Aspergillus was cultured. GM detection in BAL appears to improve the diagnosis of IA in critical patients.

Aspergilosis cardíaca en una paciente trasplantada de corazón

Background: Solid organ transplant recipients are a population at risk of invasive aspergillosis. The lung and the central nervous system are usually affected. Objectives: We report the case of a patient with proven cardiac invasive aspergillosis two years after heart transplantation, and perform a review of cardiac aspergillosis in solid organ transplant recipients. Case report A 52-year old woman received a heart transplant. Several complications appeared in the post-operative period, including the development of invasive aspergillosis in the surgical wound. She was readmitted two years later with dyspnea. A thoracic CT-scan revealed multiple lung embolisms and a mass in the retroxiphoid, invading the right atrium and the tricuspid valve. Septated hyphae invading this tissue were observed and Aspergillus fumiga-tus was subsequently isolated. Serum galactomannan determinations were negative. Antifungal therapy with vori-conazole was started. Two months later, the patient visited the hospital for a routine check-up control in good clinical condition, but with undetectable voriconazole serum levels. These levels were associated to the concomitant use of omeprazole. One year later, the patient was still receiving voriconazole and remained asymptomatic. Conclusions Invasive aspergillosis affecting the mediastinum can progress and affect the heart tissues. The use of omeprazole may be associated with the undetectable voriconazole serum levels.

Resolution of galactomannan antigenemia in a patient receiving oral voriconazole for chronic necrotizing pulmonary aspergillosis

The serologic markers of the therapeutic response of chronic necrotizing pulmonary aspergillosis (CNPA) are rarely reported. Here, we describe the changes in galactomannan (GM) antigenemia in a patient receiving oral voriconazole for CNPA, in whom a resolution of GM antigenemia to a normal level was associated with clinical improvements. The serum GM index can be an adjunctive tool for the diagnosis and monitoring of the therapeutic response of CNPA.

Serum galactomannan strongly correlates with outcome of invasive aspergillosis in acute leukaemia patients

Invasive aspergillosis (IA) remains an important cause of mortality in acute leukaemia patients. Previous studies reported that serum galactomannan (GM) levels correlate strongly with IA outcomes in patients with haematological cancers. This study aimed to clarify the usefulness of serial GM testing for outcome evaluation of IA in acute leukaemia patients. We retrospectively analysed 58 acute leukaemia patients who had IA during neutropenic period after chemotherapy and whose serum GM was serially monitored until discharge or death. The kappa correlation coefficient was used to determine the strength of correlation between GM and clinical outcome (survival or death) of IA. The correlation between clinical outcome and GM kinetics was good at week 6 [κ = 0.663, 95% confidence interval (CI): 0.465-0.861] and excellent at week 12 (κ = 0.819, 95% CI: 0.667-0.91). Survival was significantly better in patients whose GM values normalised than in patients with persistently positive GM (P < 0.0001) regardless of whether neutropenia resolved or acute leukaemia responded to chemotherapy. In neutropenic patients with acute leukaemia, serum GM correlated strongly with survival outcome of IA. This finding further supports the usefulness of the GM index as a surrogate marker for assessing IA outcome and the need for serial GM testing in therapeutic monitoring.

Serum galactomannan (GM) assay for invasive aspergillosis (IA) in acute leukemia (AL) and hematopoietic stem cell transplantation (HSCT).

6538 Background: IA is a major cause of mortality in AL and HSCT. The objectives of this study were to determine the yield of GM assay for the diagnosis of probable IA, its temporal relationship with high-resolution computed tomographic scan (HRCT) scans and correlation with mortality in patients of AL and recipients of HSCT. Methods: Consecutive neutropenic episodes among inpatients aged ≥ 15 years with a diagnosis of AL and recipients of HSCT were prospectively evaluated over 1½ years. All patients received oral itraconazole or thrice weekly IV amphotericin B (AmB) as prophylaxis. Weekly serum GM assay was performed for all subjects. Optical density index (ODI) > 0.5 for two or more samples was defined as positive. Patients with persistent fever for ≥ 96 hours on intravenous antibiotics were evaluated with HRCT chest and received empiric AmB. IA was diagnosed according to EORTC 2008 guidelines and treated with therapeutic doses of voriconazole or AmB. Results: Of the 150 episodes enrolled, AL induction constituted 51.3% (AML 35.3%, ALL 16%), high-dose cytarabine 20%, autologous HSCT 24.7%, allogeneic HSCT 2.7% and cladribine for hairy cell leukemia 1.3% episodes. Forty-three episodes (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 (39.5%). False-positivity of a single test was 54.2% but decreased to 11.2% with two results. Assessment of sensitivity was impaired due to the lack of proven cases. The lone proven case had 1/1 sample positive (ODI 2.17). In 88.2% of probable IA episodes GM was positive before HRCT at a median of 10 days (range, 1-16) earlier, while HRCT was positive before GM in the remaining 11.8% episodes at median of 3.5 days (range, 1-7) earlier. Of the 23 fatal episodes (15.3%), 17 had a diagnosis of IA. Considering only those episodes with ≥2 samples tested, fatality was 31.0% in those with at least 2 values positive for GM, compared to 13.2% in the episodes with < 2 GM samples positive (OR 2.96, 95% CI 1.09 – 8.00; p=0.04). Conclusions: In a population of high-risk patients, GM assay could identify patients with probable IA earlier than HRCT chest and also predicted a higher risk of death.

Serum and Bronchoalveolar Lavage Fluid Galactomannan Assays in Patients with Pulmonary Aspergilloma

The sensitivities of the serum and bronchoalveolar lavage galactomannan (GM) assays in 48 patients with pulmonary aspergilloma were 38% (13 of 34; 95% confidence interval [CI], 22%-56%) and 92% (33 of 36; 95% CI, 78%-98%), respectively. The positivity of serum GM assays was significantly higher in patients with hemoptysis than in those without hemoptysis (52% vs 9%; P=.02).

Pharmacokinetics and Pharmacodynamics of Posaconazole for Invasive Pulmonary Aspergillosis: Clinical Implications for Antifungal Therapy

Posaconazole is a triazole with anti-Aspergillus activity. However, little is known about the utility of posaconazole as primary therapy for invasive pulmonary aspergillosis. An in vitro model of the human alveolus was used to study the impact of minimum inhibitory concentrations (MIC) on exposure-response relationships. The pharmacokinetic-pharmacodynamic relationships of posaconazole were examined in an inhalational murine model of invasive pulmonary aspergillosis. A mathematical model was fitted to the entire data set. This model was then used to describe the relationship between drug exposure, quantified in terms of the area under the concentration time curve to MIC (AUC:MIC) and the observed antifungal effect. The posaconazole MIC was an important determinant of exposure-response relationships and accounted for a portion of the observed variance. Murine pharmacokinetics were linear for dosages 1-20 mg/kg/day. There was a dose-dependent decline in serum galactomannan concentrations, with near-maximal suppression following 20 mg/kg/day. The murine pharmacokinetic-pharmacodynamic data were well described by the mathematical model. An AUC:MIC ratio of 167 was associated with half-maximal antifungal effect. These results provide the experimental foundation for the selection of candidate posaconazole regimens for the primary treatment of invasive pulmonary aspergillosis in profoundly neutropenic hosts.

Chronic Granulomatous Disease: Lessons from a Rare Disorder

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency with X-linked or autosomal recessive inheritance involving defects in genes encoding phox proteins, which are the subunits of the phagocyte NADPH oxidase. This results in failure to produce superoxide anion and downstream antimicrobial oxidant metabolites and to activate antimicrobial proteases. Affected patients are susceptible to severe, life-threatening bacterial and fungal infections and excessive inflammation characterized by granulomatous enteritis resembling Crohn's disease and genitourinary obstruction. Early diagnosis of CGD and rapid treatment of infections are critical. Prophylaxis with antibacterial and mold-active antifungal agents and the administration of interferon-γ has significantly improved the natural history of CGD. Currently, the only cure is allogeneic hematopoietic cell transplant (HCT), although there remains controversy as to which patients with CGD should get a transplant. Allele-based HLA typing of alternative donors, improved supportive care measures, and use of reduced toxicity conditioning have resulted in event-free survival (EFS) of at least 80% even with an unrelated donor and even better when the patient has no active infections/inflammation. Gene correction of CGD would eliminate the risks of graft-versus-host disease (GVHD) and the immunoablative chemotherapy required for allogeneic HCT. Based on gene therapy trials in patients with SCID-X1, ADA-SCID, and the early experience with CGD, it is clear that at least some degree of myeloablation will be necessary for CGD as there is no inherent selective growth advantage for gene-corrected cells. Current efforts for gene therapy focus on use of lentivector constructs, which are thought to be safer from the standpoint of insertional mutagenesis and more efficient in transducing hematopoietic stem cells (HSCs).

In Vitro Activity and In Vivo Efficacy of Anidulafungin in Murine Infections by Aspergillus flavus

Anidulafungin (AFG) showed high activity against 27 strains of Aspergillus flavus by use of broth microdilution and disk diffusion methods. This drug was effective in vivo in a murine model of disseminated infection with five isolates tested. AFG was able to prolong survival and reduce tissue burden of infected mice but not able to reduce galactomannan serum concentrations. The AFG serum levels were above the corresponding minimum effective concentrations (MEC) for all of the strains tested.

Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation

AbstractInvasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P = .09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and overall survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803.

Galactomannan Testing in Bronchoalveolar Lavage Fluid Facilitates the Diagnosis of Invasive Pulmonary Aspergillosis in Patients with Hematologic Malignancies and Stem Cell Transplant Recipients

Invasive pulmonary aspergillosis (IPA) is a major cause of mortality in patients with stem cell transplants and hematologic malignancies. Timely diagnosis of IPA improves survival but is difficult to make. We evaluated the effectiveness of bronchoalveolar lavage (BAL) galactomannan (GM) in diagnosing IPA in these populations by retrospectively reviewing records of 67 consecutive patients, in whom 89 BAL GM tests were performed. For patients with IPA, only the first BAL sample linked to the IPA episode was analyzed. Eighty samples were associated with proven, 12 with probable, and 32 with possible invasive fungal infections (IFI), and 37 were associated with no IFI. Among patients with IFIs, 4 had proven, 11 probable, and 32 possible IPA. Using BAL GM ≥ 0.5 (cutoff for serum GM) and ≥ 0.85 (optimal cutoff identified by receiver-operating characteristic curve), the sensitivity in diagnosing proven or probable IPA was 73% (11/15) and 67% (10/15), respectively, and specificity was 89% (33/37) and 95% (35/37). At these cutoffs, positive and negative predictive values were 73% (11/15) and 83% (10/12), and 89% (33/37) and 87% (35/40), respectively. BAL GM was more sensitive than cytology (0%, 0/14), BAL culture (27%, 4/15), transbronchial biopsy (40%, 2/5), or serum GM (67%, 10/15) for diagnosing IPA. BAL GM was ≥ 0.85 and ≥ 0.5 in 86% (6/7) and 100% (7/7) of patients with proven or probable IPA who received a mold-active agent for ≤ 3 days. BAL GM added sensitivity to serum GM and other means of diagnosing IPA, and was not impacted by short courses of mold-active agents.

Positive Results of Serum Galactomannan Assays and Pulmonary Computed Tomography Predict the Higher Response Rate of Empirical Antifungal Therapy in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Invasive fungal disease (IFD) is a leading cause of infection-related mortality among patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although the mortality of IFD has been decreased with empirical antifungal therapy in this population, overtreatment remains a problem, for the persistent or recurrent fever is nonspecific for an IFD. Hence, we explored retrospectively the value of incorporating serum galactomannan (GM) test and pulmonary high-resolution computed tomography (HRCT) as predictors for higher response rate of empirical treatment. In our study, all of 124 patients after allo-HSCT received empirical antifungal therapy when the persistent or recurrent fever developed after receiving broad-spectrum antibiotics. Meanwhile, the levels of serum GM were monitored twice weekly and pulmonary HRCT was performed serially. It showed that the response rate of empirical antifungal therapy was higher in patients with positive results of serum GM tests and/or chest CT scan than that in all patients (66.1% versus 44.6%, P = .008). Moreover, only 10 of 55 patients with both negative GM tests and pulmonary HRCT responded to empirical treatment, and 7 of these 10 patients did not take antifungal agents for prophylaxis. It suggested that these 2 diagnostic tools could not predict patients without adequate Candida prophylaxis well. Thus, we concluded that serum GM assays and pulmonary CT scan could find out patients who really need empirical antifungal therapy, which resulted in improving the efficiency of the treatment.

A retrospective study of 3 cases of severe asthma with fungal sensitization

to describe the clinical features and diagnosis of severe asthma with fungal sensitization (SAFS). the clinical data of 3 patients of SAFS from this hospital were presented, and the related literatures reviewed. the 3 patients, 1 male and 2 females, aging 55, 52 and 61 years respectively, had a history of asthma for 4 - 40 years. All of them presented with severe asthma symptoms, and were found to have fungal sensitization by skin prick testing. Their serum IgE level was less than 1000 IU/ml. A. fumigatus was positive from sputum cultures. There were no radiological abnormalities such as pulmonary infiltrates and bronchiectasis by HRCT in all cases. The serum galactomannan (GM) was positive in 2 patients. After diagnosis, they received additional antifungal therapy for 4 - 22 months, respectively, and the prognosis was good. SAFS should be considered in patients with severe asthma and sensitization to fungi but without elevation of serum IgE. Adjunctive antifungal therapy is beneficial for asthma control.

Probable Invasive Aspergillosis without Prespecified Radiologic Findings: Proposal for Inclusion of a New Category of Aspergillosis and Implications for Studying Novel Therapies

The European Organization for Research and Treatment of Cancer (EORTC) and the Mycosis Study Group (MSG) definition of invasive aspergillosis used in clinical trials lacks sensitivity. We hypothesize that giving lower weight to the prespecified radiologic findings in patients with a positive serum galactomannan index test result will improve the definition's diagnostic sensitivity. The medical records of 121 patients with 125 cases of invasive aspergillosis treated at a referral cancer institute from January 2003 through December 2009 were reviewed. Aspergillosis was diagnosed as EORTC-MSG proven or probable (controls, 83) or probable invasive aspergillosis without prespecified radiologic criteria (cases, 42). The latter differed from the former by the inclusion of patients whose pulmonary infiltrates, although well described in invasive aspergillosis, do not fulfill EORTC-MSG invasive aspergillosis requirements. The host, clinical, and mycologic characteristics and survival of cases and controls served as end points. A total of 114 (91%) of 125 patients had multiple myeloma. Patients had a median age was 65 years (range, 26-81 years), and 74 were male. All had received antineoplastic therapy, including stem cell transplantation (58 [46%]). Aspergillosis involved lungs (88 patients), sinuses (9 patients), or both (28 patients). Except for higher median baseline platelet count and shorter duration of neutropenia among cases, there were no statistically significant differences between groups on all predefined end points, including 4-, 6-, and 12-week survival. Eleven of 26 cases were reclassified as controls on the basis of subsequent imaging. Except for less well-circumscribed consolidations, the host, clinical, radiologic, and mycologic characteristics and outcome of patients with probable invasive aspergillosis but without prespecified radiologic criteria are similar to those with EORTC-MSG invasive aspergillosis. Enrolling such patients in clinical trials of novel therapies will increase the pool of eligible study participants and improve trial speed and efficiency.