Invasive Pulmonary Aspergillosis in Hospitalized Hematopoietic Stem Cell Transplantation Recipients: Outcomes Based on the United States National Readmission Database.

BACKGROUND AND OBJECTIVE: Hematopoietic stem cell transplant (HSCT) is a well-established treatment for hematologic malignancies and certain autoimmune and congenital conditions. HSCT is associated with immunocompromise and increased risk of infections. This study assessed whether invasive pulmonary aspergillosis (IPA) affects in-hospital mortality and 30-day readmission among HSCT patients. A secondary objective was to examine potential differences in complications between HSCT with and without IPA. MATERIALS AND METHODS: A retrospective study of a nationally representative cohort of hospital admissions was conducted, with data collected from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database between 2013 and 2019. The International Classification of Diseases, 10th revision (ICD-10), and 9th revision (ICD-9) diagnostic codes were used to identify patients with IPA and HSCT. All adult patients ≥18 years were included in the study. RESULTS: There were 90,451 hospitalizations for HSCT from 2013 to 2019; 89,331 (98.8%) had HSCT without IPA, while 1092 (1.2%) hospitalizations had HSCT with IPA. The in-hospital mortality for HSCT-IPA was higher compared to HSCT without IPA (18.3% vs. 4.2%; p < 0.001). HSCT-IPA had a significantly higher 30-day readmission rate (36.2%) than that of HSCT without IPA (24.0%). HSCT-IPA also had a higher mean cost of admission ($303,437) than that of HSCT without IPA ($57,587).The HSCT-IPA group had higher multi-organ complications, including respiratory failure (51.3% vs. 13.5%, p < 0.001), sepsis (38.2% vs. 18.5%, p < 0.001), septic shock (16.1% vs. 5.1%, p < 0.001), need for mechanical ventilation (21.1% vs. 5.1% p < 0.001), non-invasive positive pressure ventilation (4.9% vs. 2.5%, p < 0.001), and intensive-care unit admission (21.8% vs. 6.1% p < 0.001). CONCLUSION: IPA is a rare but severe complication associated with HSCT, with higher in-hospital mortality, complications due to multi-organ failure, readmission rates, and cost of hospitalization when compared to HSCT without IPA.

Invasive Pulmonary Aspergillosis Successfully Treated with Granulocyte Transfusions Followed by Hematopoietic Stem Cell Transplantation in a Patient with Severe Childhood Aplastic Anemia.

Granulocyte transfusions (GTX) have been used in patients with neutropenia or neutropenia associated with invasive fungal infection. An 11-year-old girl with severe aplastic anemia (SAA) received immunosuppressive therapy (IST) with rabbit antithymocyte globulin, cyclosporine, and granulocyte colony-stimulating factor. However, IST was not effective and her condition became complicated with life-threatening invasive pulmonary aspergillosis. Owing to the necessity for early neutrophil recovery to resolve the infection, GTX were performed, followed by bone marrow transplantation (BMT) from her mother with human leukocyte antigen-B locus mismatch. Her dyspnea improved and she eventually became afebrile after the initiation of GTX. Despite engraftment failure following BMT, successful engraftment was achieved by salvage therapy with peripheral blood stem cell transplantation. Chest computed tomography scan obtained 4 months after BMT revealed marked improvement in pneumonia. The current case illustrates that GTX may be useful in controlling invasive fungal infections before hematopoietic stem cell transplantation in patients with SAA.

CAR T cells targeting Aspergillus fumigatus are effective at treating invasive pulmonary aspergillosis in preclinical models.

Aspergillus fumigatus is a ubiquitous mold that can cause severe infections in immunocompromised patients, typically manifesting as invasive pulmonary aspergillosis (IPA). Adaptive and innate immune cells that respond to A. fumigatus are present in the endogenous repertoire of patients with IPA but are infrequent and cannot be consistently isolated and expanded for adoptive immunotherapy. Therefore, we gene-engineered A. fumigatus-specific chimeric antigen receptor (Af-CAR) T cells and demonstrate their ability to confer antifungal reactivity in preclinical models in vitro and in vivo. We generated a CAR targeting domain AB90-E8 that recognizes a conserved protein antigen in the cell wall of A. fumigatus hyphae. T cells expressing the Af-CAR recognized A. fumigatus strains and clinical isolates and exerted a direct antifungal effect against A. fumigatus hyphae. In particular, CD8+ Af-CAR T cells released perforin and granzyme B and damaged A. fumigatus hyphae. CD8+ and CD4+ Af-CAR T cells produced cytokines that activated macrophages to potentiate the antifungal effect. In an in vivo model of IPA in immunodeficient mice, CD8+ Af-CAR T cells localized to the site of infection, engaged innate immune cells, and reduced fungal burden in the lung. Adoptive transfer of CD8+ Af-CAR T cells conferred greater antifungal efficacy compared to CD4+ Af-CAR T cells and an improvement in overall survival. Together, our study illustrates the potential of gene-engineered T cells to treat aggressive infectious diseases that are difficult to control with conventional antimicrobial therapy and support the clinical development of Af-CAR T cell therapy to treat IPA.

Hematopoietic Stem Cell Transplantation Cures Therapy-refractory Aspergillosis in Chronic Granulomatous Disease.

BACKGROUND: Pulmonary invasive aspergillosis is a frequent and life-threatening complication for patients with chronic granulomatous disease (CGD). Despite combined treatment with several groups of antifungal agents, conservative treatment of invasive aspergillosis often remains refractory. Pulmonary invasive aspergillosis is often treated by surgical resection of consolidated lobes or segments, donor granulocyte transfusions and allogeneic hematopoietic stem cell transplantation (HSCT). These options are not mutually exclusive and often combined. METHODS AND RESULTS: We here describe the treatment of 3 patients with CGD who received HSCT upon active pulmonary invasive aspergillosis: Two of them received HSCT as salvage therapy for refractory aspergillosis, and 1 patient received elective HSCT in infancy but developed pulmonary aspergillosis during secondary graft failure. Based on our experience and available literature, we discuss indication as well as timing of HSCT, granulocyte transfusions and surgery in patients with CGD and pulmonary invasive aspergillosis. CONCLUSIONS: Upon diagnosis with invasive aspergillosis in CGD, we propose to start antifungal treatment and preparation for HSCT at the same time. Remission of pulmonary invasive aspergillosis before HSCT remains preferable but is not mandatory. When pulmonary aspergillosis in patients with CGD remains refractory for longer than 3 months on conservative treatment, HSCT without prior surgery or accompanying granulocyte transfusions is a feasible option.

Clinical utility of the updated European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and the Mycoses Study Group Education and Research Consortium computed tomography criteria of invasive pulmonary aspergillosis in hematological malignancies.

Invasive pulmonary aspergillosis is a life-threatening complication in the cases of patients with hematologic malignancies. In December 2019, the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and the Mycoses Study Group Education and Research Consortium published a revision and an update of the consensus definitions of invasive fungal disease. The aim of this study was to evaluate the signs and radiologic patterns of early-stage invasive pulmonary aspergillosis in computed tomography in patients with hematologic entities according to the latest criteria.This retrospective analysis of a baseline high-resolution computed tomography included neutropenic patients with hematological malignancies and probable invasive pulmonary aspergillosis. The data were collected between the years 2017 and 2019. Computed tomography was performed within 72 h from the beginning of clinical symptoms: fever, dyspnea or nonproductive cough. CT scans were analyzed by two independent radiologists according to the standardized protocol based on predefined criteria.All 35 evaluated patients had typical lesions for early-stage invasive aspergillosis. Wedge-shaped infiltrates were noted in 48.6% of patients. In this group, 40% of patients had coexisting atypical radiological findings. In 11.4% of patients, wedge-shape consolidations were noted as the only type of lesions.Employment of the latest EORTC/MSG criteria increased diagnostic value of the baseline high resolution computed tomography in our study group by 11.4%.

Pulmonary Aspergillosis: What the Generalist Needs to Know.

Aspergillus spp. is a ubiquitous mold found commonly in our environment that can cause a spectrum of pulmonary disorders, ranging from a hypersensitivity reaction to an acutely invasive disease with significant mortality. Allergic bronchopulmonary aspergillosis results from airway hypersensitivity from aspergillus colonization almost exclusively in patients with asthma and cystic fibrosis. Chronic pulmonary aspergillosis typically presents in immunocompetent patients with underlying lung pathology. Treatment is primarily with antifungal agents; however, other measures such as surgical resection may be necessary. Invasive pulmonary aspergillosis is a severe infection in immunocompromised patients and is characterized by invasion of pulmonary vasculature by the Aspergillus hyphae. Recent advances in the diagnosis and management of invasive pulmonary aspergillosis include emerging risk factors such as critically ill patients, and those with chronic obstructive pulmonary disease and liver disease. In addition, noninvasive biomarkers have made it easier to suspect and diagnose invasive pulmonary aspergillosis. There are more effective and better-tolerated antifungal agents that have improved patient outcomes. This review introduces the spectrum of pulmonary aspergillosis geared toward generalists, including disease manifestations, most recent diagnostic criteria, and first-line treatment options. Involving a multidisciplinary team is vital to the early diagnosis and management of these diseases.

Invasive pseudomembranous upper airway and tracheal Aspergillosis refractory to systemic antifungal therapy and serial surgical debridement in an Immunocompetent patient.

BACKGROUND: The development of respiratory infections secondary to Aspergillus spp. spores found ubiquitously in the ambient environment is uncommon in immunocompetent patients. Previous reports of invasive upper airway aspergillosis in immunocompetent patients have generally demonstrated the efficacy of treatment regimens utilizing antifungal agents in combination with periodic endoscopic debridement, with symptoms typically resolving within months of initiating therapy. CASE PRESENTATION: A 43-year-old previously healthy female presented with worsening respiratory symptoms after failing to respond to long-term antibiotic treatment of bacterial sinusitis. Biopsy of her nasopharynx and trachea revealed extensive fungal infiltration and Aspergillus fumigatus was isolated on tissue culture. Several months of oral voriconazole monotherapy failed to resolve her symptoms and she underwent mechanical debridement for symptom control. Following transient improvement, her symptoms subsequently returned and failed to fully resolve in spite of increased voriconazole dosing and multiple additional tissue debridements over the course of many years. CONCLUSIONS: Invasive upper airway aspergillosis is exceedingly uncommon in immunocompetent patients. In the rare instances that such infections do occur, combinatorial voriconazole and endoscopic debridement is typically an efficacious treatment approach. However, some patients may continue to experience refractory symptoms. In such cases, continued aggressive treatment may potentially slow disease progression even if complete disease resolution cannot be achieved.

Clinical features of fatal severe fever with thrombocytopenia syndrome that is complicated by invasive pulmonary aspergillosis.

INTRODUCTION: Severe fever with thrombocytopenia syndrome (SFTS) has been prevalent in parts of Asia during recent years. However, SFTS with invasive pulmonary aspergillosis (IPA) is rare, and it is important to understand its clinical features. MATERIALS AND METHODS: Total four cases of SFTS with IPA are reviewed and detailing the disease progression, treatment options, and prognosis were summarized and analyzed. RESULTS: The patients with SFTS-associated IPA first presented with fever, gastrointestinal symptoms, thrombocytopenia, leukopenia, and multiple organ failure. After 1-2 weeks, the patients developed mild polypnea and wheezing rales, and quickly developed dyspnea and respiratory failure. Tracheal intubation was usually performed, but did not relieve the intractable airway spasm and pulmonary ventilation failure. Bronchoscopy confirmed that the antifungal treatment was ineffective and the aspergillosis had worsened. All patients died of type 2 respiratory failure caused by continued airway obstruction and spasticity. CONCLUSIONS: Given the high mortality rate in this series, there is a need for increased awareness of SFTS-associated IPA. Additional examinations should be performed in these cases, and early-stage antifungal treatment with organ support may be helpful.

Invasive Aspergillosis After Kidney Transplant-Treatment Approach.

AIM: Aim of the article was to present a case of post transplantation invasive aspergillosis, successfully treated with conservative and surgical treatment. CASE REPORT: Patient, male, 44 years old, with second kidney transplant, required special preparation therapy, because he was sensitized, with concentration of Panel Reactive Antibody (PRA) class I 11% and PRA class II 76%. On the day of transplantation, induction was done with anti-thymocyte globulin (ATG) and glucocorticosteroids. After transplantation, plasmapheresis with ATG was performed. On the fourth day patient was anuric. Fine-needle biopsy of the graft was performed and showed positive CD4 antibodies for peritubular capillaries and humoral rejection. 14 plasmaphereses through 14 days, were negative and ATG treatment was suspended completely. Full therapeutic dosage of tacrolimus and mycophenolate mofetil were given during treatment. Four days after treatment patient was stable, but next day clinical status had worsened with dyspnea and fever. In sputum, spores of Aspergillus species were microscopically found, and radiologically by computerised tomography. Caspofungin was administered for seven days. Voriconazole therapy was given for first ten days by intravenous route and after then orally. Even with this treatment, there was no improvement in clinical picture, while CT scan of the lungs showed abscess collection in right lung. Lobectomy was performed and pus collection was found. After graft-nephroctomy, patient was treated with continous veno-venous hemodiafiltration (CV-VHDF) dialyses, with constant voriconazole therapy for the next three months (200mg two times per day). After one month of diagnosis, Galactomannan (GM) test was negative. CONCLUSION: Although highly sensitized patients, those who are on hemodialysis, in preparation for transplantation, receive intensive immunosuppressive therapy that suppress the immune system. Occurrence of secondary fungal infections especially infection by aspergillosis, is cause of high mortality of infected. Application GM test that detects existence of antibodies against Aspergillus antigens and usage of different type of immunosuppressive preparation can increase longevity of graft and patients in solid organ transplantation program. Aspergillosis is treated with voriconazole and surgery, and sometimes graft-nephrectomy if needed. Recommendation is that in all immunocompromised hosts and organ transplant recipient should have been tested with GM test.

Clinical outcome and prognostic factors associated with invasive pulmonary aspergillosis: An 11-year follow-up report from Taiwan.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) has high mortality rate but prognostic factors are not well established. The aim of our study was to evaluate the trend in in-hospital mortality over a period of 11 years and identify factors affecting the clinical outcomes of patients with IPA. METHOD: We conducted a nationwide inpatient population study using data from the Taiwan National Health Insurance Research Database. A total of 407 IPA patients from 2002 to 2012 were included in the study. Differences in demographics, comorbidities, and treatment were evaluated between in-hospital death group and survival group. Multivariate analysis was also performed to identify risk factors for mortality. RESULT: Male patients represented 63.14% of the patients (n = 257) and the mean age was 53.15 ± 20.93 years. Hematological cancer (n = 216, 53.07%) and diabetes mellitus (n = 75, 18.43%) were the most common underlying conditions. The overall case fatality rate was 30.22% with female slightly higher then male (32.67% versus 28.79%). The in-hospital case fatality rate increased since 2002 and peaked in 2006. It then declined over time with an in-hospital mortality of 25% in 2012. The in-hospital death group had a higher intubation rate (p<0.0001), a longer ICU stay (p = 0.0062), higher percentages of DM (p = 0.0412) and COPD (p = 0.0178), and a lower percentage of hematological cancer (p = 0.0079) as compared to survivor. The in-hospital death group was more likely to have steroid treatment (p<0.0001), develop acute renal failure (p<0.0001) and other infectious diseases (p = 0.0008) during hospitalization. Multivariate analysis identified female gender, older age (≥ 65 years old), intubation, bone marrow transplantation, acute renal failure, other infectious diseases and steroid use as predictive factors for mortality. CONCLUSION: The present study shows the trend in mortality among patients with IPA over an 11-year period. Female gender, older age, intubation, bone marrow transplantation, acute renal failure, other infectious diseases and steroid use were identified as risk factors for mortality.

Prospects for adoptive T-cell therapy for invasive fungal disease.

PURPOSE OF REVIEW: Invasive fungal disease (IFD) is a cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. As more potent broad-spectrum antifungal agents are used in prophylaxis, drug resistance and less common fungal species have increased in frequency. Here we review current treatments available for IFD and examine the potential for adoptive T-cell treatment to enhance current therapeutic choices in IFD. RECENT FINDINGS: There is growing evidence supporting the role of T cells as well as phagocytes in antifungal immunity. T cells recognizing specific antigens expressed on fungal morphotypes have been identified and the role of T-cell transfer has been explored in animal models. The clinical efficacy of adoptive transfer of antigen-specific T cells for prophylaxis and treatment of viral infections post-HSCT has raised interest in developing good manufacturing practice (GMP)-compliant methods for manufacturing and testing fungus-specific T cells after HSCT. SUMMARY: As the outcomes of IFD post-HSCT are poor, reconstitution of antifungal immunity offers a way to correct the underlying deficiency that has caused the infection rather than simply pharmacologically suppress fungal growth. The clinical development of fungus specific T cells is in its early stages and clinical trials are needed in order to evaluate safety and efficacy.

Successful Treatment of Combined Aspergillus and Cytomegalovirus Abscess in Brain and Lung After Liver Transplant for Toxic Fulminant Hepatitis.

Invasive aspergillosis is one of the most important and fatal complications after liver transplant, especially in patients with involvement of the central nervous system. We present a case of a patient who developed cerebral and pulmonary aspergillosis, coinfected with cytomegalovirus, after liver transplant for toxic fulminant hepatitis. The patient was treated successfully with neurosurgical intervention and voriconazole. Voriconazole is considered more effective in cerebral aspergillosis than other anti-fungal agents due to the greater penetration into central nervous system and higher cerebrospinal fluid and brain tissue levels.

Septic-Metastasizing Aspergillus-Encephalitis Mimicking Massive Cerebral Infarction in a Heart Transplant Recipient: A Case Report.

Invasive fungal infection after solid-organ transplantation is known as a severe complication and carries with it a high risk of infection-related mortality. Among patients after heart transplant Aspergillus species most often cause atypical pneumonia. The incidence of invasive aspergillosis after heart transplant has been reported from 3% to 14%. It is the opportunistic pathogen with the highest mortality, ranging from 50% to 80%. Prompt antifungal therapy is crucial, but rapid diagnostic procedures with sufficient sensitivity and specificity are lacking at the moment. We present a rare case of a patient with massive metastasizing invasive aspergillosis within 1 month after heart transplant, undetected before death.

Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management.

Chronic pulmonary aspergillosis (CPA) is an uncommon and problematic pulmonary disease, complicating many other respiratory disorders, thought to affect ~240 000 people in Europe. The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), which untreated may progress to chronic fibrosing pulmonary aspergillosis. Less common manifestations include: Aspergillus nodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (<3 months) usually found in moderately immunocompromised patients, which should be managed as invasive aspergillosis. Few clinical guidelines have been previously proposed for either diagnosis or management of CPA. A group of experts convened to develop clinical, radiological and microbiological guidelines. The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence of Aspergillus infection (microscopy or culture from biopsy) or an immunological response to Aspergillus spp. and exclusion of alternative diagnoses, all present for at least 3 months. Aspergillus antibody (precipitins) is elevated in over 90% of patients. Surgical excision of simple aspergilloma is recommended, if technically possible, and preferably via video-assisted thoracic surgery technique. Long-term oral antifungal therapy is recommended for CCPA to improve overall health status and respiratory symptoms, arrest haemoptysis and prevent progression. Careful monitoring of azole serum concentrations, drug interactions and possible toxicities is recommended. Haemoptysis may be controlled with tranexamic acid and bronchial artery embolisation, rarely surgical resection, and may be a sign of therapeutic failure and/or antifungal resistance. Patients with single Aspergillus nodules only need antifungal therapy if not fully resected, but if multiple they may benefit from antifungal treatment, and require careful follow-up.

Multicenter evaluation of a lateral-flow device test for diagnosing invasive pulmonary aspergillosis in ICU patients.

INTRODUCTION: The incidence of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is increasing, and early diagnosis of the disease and treatment with antifungal drugs is critical for patient survival. Serum biomarker tests for IPA typically give false-negative results in non-neutropenic patients, and galactomannan (GM) detection, the preferred diagnostic test for IPA using bronchoalveolar lavage (BAL), is often not readily available. Novel approaches to IPA detection in ICU patients are needed. In this multicenter study, we evaluated the performance of an Aspergillus lateral-flow device (LFD) test for BAL IPA detection in critically ill patients. METHODS: A total of 149 BAL samples from 133 ICU patients were included in this semiprospective study. Participating centers were the medical university hospitals of Graz, Vienna and Innsbruck in Austria and the University Hospital of Mannheim, Germany. Fungal infections were classified according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS: Two patients (four BALs) had proven IPA, fourteen patients (sixteen BALs) had probable IPA, twenty patients (twenty-one BALs) had possible IPA and ninety-seven patients (one hundred eight BALs) did not fulfill IPA criteria. Sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratios for diagnosing proven and probable IPA using LFD tests of BAL were 80%, 81%, 96%, 44% and 17.6, respectively. Fungal BAL culture exhibited a sensitivity of 50% and a specificity of 85%. CONCLUSION: LFD tests of BAL showed promising results for IPA diagnosis in ICU patients. Furthermore, the LFD test can be performed easily and provides rapid results. Therefore, it may be a reliable alternative for IPA diagnosis in ICU patients if GM results are not rapidly available. TRIAL REGISTRATION: ClinicalTrials.gov NCT02058316. Registered 20 January 2014.

Systematic review of immunotherapy for chronic rhinosinusitis.

BACKGROUND: Immunotherapy (IT) has been well established as an effective treatment for allergic rhinitis (AR), but little is known about the benefits of IT on clinical outcomes of comorbid chronic rhinosinusitis (CRS). The goal of this publication is to systematically review the literature regarding outcomes of IT in patients with atopic CRS. METHODS: A systematic review of the literature was conducted including studies that assessed the efficacy of IT on clinical outcome measures in CRS including without polyp, with polyp, and allergic fungal rhinosinusitis subgroups. Excluded articles were those only reporting outcomes specific to asthma or AR. RESULTS: Seven studies met the inclusion and exclusion criteria for this review, none of which were randomized controlled trials. Generally, symptom scores improved in patients treated with IT when compared with baseline data and control patients. Objective endoscopic exam measures improved with IT treatment in short-term studies. Significant improvements were observed in radiographic assessments, and there was a decreased necessity for revision surgery, interventional office visits, and intranasal and oral steroid use. CONCLUSION: Conclusions are limited by the paucity of available data on the efficacy of IT for treating CRS-specific outcome measures. There is weak evidence to support the use of IT as an adjunctive treatment in CRS patients, particularly in the postoperative period.

Chapter 8: Invasive fungal rhinosinusitis.

Invasive fungal rhinosinusitis (IFRS) is a disease of the paranasal sinuses and nasal cavity that typically affects immunocompromised patients in the acute fulminant form. Early symptoms can often mimic rhinosinusitis, while late symptoms can cause significant morbidity and mortality. Swelling and mucosal thickening can quickly progress to pale or necrotic tissue in the nasal cavity and sinuses, and the disease can rapidly spread and invade the palate, orbit, cavernous sinus, cranial nerves, skull base, carotid artery, and brain. IFRS can be life threatening if left undiagnosed or untreated. While the acute fulminant form of IFRS is the most rapidly progressive and destructive, granulomatous and chronic forms also exist. Diagnosis of IFRS often mandates imaging studies in conjunction with clinical, endoscopic, and histopathological examination. Treatment of IFRS consists of reversing the underlying immunosuppression, antifungal therapy, and aggressive surgical debridement. With early diagnosis and treatment, IFRS can be treated and increase patient survival.

Granulocyte transfusions in hematologic malignancy patients with invasive pulmonary aspergillosis: outcomes and complications.

BACKGROUND: Granulocyte transfusions (GTXs) have been used successfully as an adjunctive treatment option for invasive infections in some neutropenic patients with underlying hematologic malignancy (HM). PATIENTS AND METHODS: We sought to determine the impact of GTX as an adjunct to antifungal therapy in 128 patients with HM and prolonged neutropenia (≥14 days) with a proven or probable invasive aspergillosis (IA) infection by retrospectively reviewing our institutional database. RESULTS: Fifty-three patients received GTX and 75 did not. By univariate analysis, patients with invasive pulmonary aspergillosis who received GTX were less likely to respond to antifungal therapy (P = 0.03), and more likely to die of IA (P = 0.009) when compared with the non-GTX group. Among patients who received GTX, 53% developed a pulmonary reaction. Furthermore, IA-related death was associated with the number of GTX given (P = 0.018) and the early initiation of GTX within 7 days after starting antifungal therapy (P = 0.001). By multivariate competing risk analysis, patients who received GTX were more likely to die of IA than patients who did not receive GTX (P = 0.011). CONCLUSIONS: Our study suggests that GTX does not improve response to antifungal therapy and is associated with worse outcomes of IA infection in HM patients, particularly those with pulmonary involvement.