Episodes Of Invasive Fungal Disease Research Articles

Invasive fungal disease in children with solid tumors: An Australian multicenter 10-year review.

Invasive fungal disease (IFD) occurs less frequently during treatment for solid compared to hematological malignancies in children, and risk groups are poorly defined. Retrospective national multicenter cohort data (2004-2013) were analyzed to document prevalence, clinical characteristics, and microbiology of IFD. Amongst 2067 children treated for solid malignancy, IFD prevalence was 1.9% overall and 1.4% for proven/probable IFD. Of all IFD episodes, 42.5% occurred in patients with neuroblastoma (prevalence 7.0%). Candida species comprised 54.8% of implicated pathogens in proven/probable IFD. In children with solid tumors, IFD is rare, and predominantly caused by yeasts.Routine prophylaxis may not be warranted.

Invasive fungal infections in children with leukemia in a tertiary hospital in Oman: An eight-year review.

Invasive fungal disease (IFD) is a common and serious consequence of leukemia in children and the incidence of these infections has increased due to chemotherapy. This study aimed to present the epidemiology of IFD in a cohort of children with leukemia from a tertiary reference institution in Oman. A retrospective study of IFDs in pediatric patients below 13 years of age with newly diagnosed or relapsed leukemia was conducted at the Royal Hospital in Muscat, Oman. From 2010 to 2017, IFD episodes in children with leukemia were evaluated retrospectively, considering age, gender, type of leukemia, chemotherapy regimen, IFD detection phase, neutropenia, prevention, diagnostic method, and treatment. Between 2010 and 2017, 198 children with leukemia were admitted and treated at Royal Hospital. Invasive fungal infection (IFI) was diagnosed in 32 patients out of 198 (16.1%), and IFI was defined as probable and proven in 53% (n=17) and 47% (n=15) of the cases, respectively. At 1.1:1, the male-to-female ratio was roughly equal. According to chest computed tomography scans, 65.6% of patients had radiological features of fungal infections. Positive fungal cultures were found in the bronchoalveolar lavage of three patients, 37.5% of whom had positive blood cultures, and 3% had positive urine cultures as a neonatal invasive candidiasis. In three patients, invasive aspergillosis caused pulmonary IFD, accounting for 9.3% of all infection sites. Candidaemia was found in 28% of IFD patients, and the most common organism was Candida tropicalis (15.6%), followed by Candida parapsilosis (6.25%). Furthermore, the major risk factor was febrile neutropenia. In children with leukemia, invasive fungal infection is common and serious. Despite aggressive treatment, mortality among these high-risk patients remains high.

Infectious Complications of Bispecific Antibody Therapy in Patients with Multiple Myeloma

Introduction Infection is a leading contributor to morbidity in heavily treated patients with multiple myeloma (MM) with severe infection rates of up to 30% reported (Lim et. al. Clin Lymphoma Myeloma Leuk 2021). Bispecific antibody (BsAb) therapy is increasingly used in the treatment of multiple myeloma (MM) patients, but the infectious risks and optimal antimicrobial prophylaxis are not well-characterised. A retrospective observational study was conducted to describe the epidemiology, infectious complications, and outcomes to better guide antimicrobial prophylaxis and empiric treatment in this cohort. Methods All MM patients who received BsAb therapy at the Peter MacCallum Cancer Centre between 1st January 2018 to 30th May 2022 were included. Retrospective chart review of patients was conducted, and demographic, clinical, and microbiological data related to disease and infection episodes were collected. Complications of BsAb therapy such as cytokine release syndrome (CRS) were defined according to published criteria. Episodes of infection were graded by CTCAE criteria, and categorised as microbiologically-defined (MDI), clinically-defined (CDI) or fever of unknown focus (FUO) as defined by presence of fever and the absence of compatible microbiology or focal symptoms. Patients were followed up for 6 months post last BsAb dose, until next line of treatment, or death. Descriptive statistics were utilised to summarise clinical data and univariate and multivariate logistic regression performed to identify factors associated with MDI. Statistical analysis was conducted on Rstudio with p<0.05 considered statistically significant. Results: Overall, 39 patients were included. Patients were predominantly male (24, 62%), with a mean age of 62 (range: 27-78). The majority (67%) had IgG type myeloma, 28% had an International Staging System (ISS) score of 3 and had a median of 6 (IQR 4-7) lines of therapy prior to BsAb. Patients received a median of 5 (IQR 2-11) cycles of therapy and CRS occurred in 28 (72%) patients. Median duration of neutropenia and lymphopenia <1.0x109/L was 1 (IQR 0-3) and 22 (13-61) days respectively. Baseline characteristics are presented in Table 1. Of the 39 patients, 35 (90%) had at least 1 episode of infection (MDI, CDI, FUO), 15 (38%) had an MDI, and 16 (41%) had a grade 3 or higher infection episode. There was a total of 111 infection episodes and prior valaciclovir prophylaxis was administered in 104 (94%), trimethoprim/sulfamethoxazole in 104 (94%) and antifungals in 38 (34%) episodes. Cumulative prednisone-equivalent dose in the preceding 30 days was median of 266.7mg (IQR 106.7-266.7). Of these 111 episodes, 33 (30%) were MDI, 43 (39%) were CDI, and 35 (32%) were FUO (Table 2). Respiratory system was the commonest site of infection (46, 41%). Of the MDI, viral infections were commonest (22, 67%), particularly rhinovirus/enterovirus (8, 36%), followed by cytomegalovirus (4, 18%) and adenovirus (4, 18%). Bacterial infections were Gram negative in 12 (80%) and Gram positive in 3 (20%). There were no episodes of invasive fungal disease. Majority of FUO were likely CRS (31, 89%). Episodes occurred during a median of 2 (IQR 1-7) cycles of therapy. Hospital admission was associated with 63 (57%) episodes with a median (IQR) length of stay of 4 (3-6) days. Intensive care admission was required in 4 (4%) episodes and all-cause mortality was 3%. Baseline clinical variables age, functional status (ECOG), international staging system stage, lines of therapy, CRS, and its treatment were not found to be associated with increased risk for MDI on univariate or multivariate logistic regression. Conclusions: Infection remains a clinically significant burden in heavily-treated MM patients on BsAb therapy. Clinically diagnosed, respiratory tract infections were most frequently diagnosed. Viral infections were the most common type of MDI identified, facilitating targeting of prevention and surveillance measures. Future larger studies are required to define associated risks for infection. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Introducing 1,3‐beta‐d‐glucan for screening and diagnosis of invasive fungal diseases in Australian high‐risk haematology patients: is there a clinical benefit?

Early, accurate diagnosis of invasive fungal disease (IFD) improves clinical outcomes. 1,3-beta-d-glucan (BDG) (Fungitell, Associates of Cape Cod, Inc., Falmouth, MA, USA) detection can improve IFD diagnosis but has been unavailable in Australia. To assess performance of serum BDG for IFD diagnosis in a high-risk Australian haematology population. We compared the diagnostic value of weekly screening of serum BDG with screening by Aspergillus polymerase chain reaction and Aspergillus galactomannan in 57 at-risk episodes for the diagnosis of IFD (proven, probable, possible IFD). IFD episodes were: proven (n = 4); probable (n = 4); possible (n = 18); and no IFD (n = 31). Using two consecutive BDG results of ≥80 pg/mL to call a result 'positive', the sensitivity, specificity, positive predictive value and negative predictive value was 37.5%, 64.5%, 23.1% and 80.7% respectively. For invasive aspergillosis, test performance increased to 50%, 90.3%, 57.1% and 87.5% respectively if any two of serum BDG/Aspergillus polymerase chain reaction/galactomannan yielded a 'positive' result. In proven/probable IFD, five of eight episodes returned a positive BDG result earlier (mean 6.6 days) than other diagnostic tests. False-negative BDG results occurred in three of eight episodes of proven/probable IFD, and false positive in 10 of 31 patients with no IFD. Erratic patterns of BDG values predicted false positive results (P = 0.03). Using serum BDG results, possible IFD were reassigned to either 'no' or 'probable' IFD in 44% cases. Empiric anti-fungal therapy use may have been optimised by BDG monitoring in 38.5% of courses. The BDG assay can add diagnostic speed and value but was hampered by low sensitivity and positive predictive value in Australian haematology patients.

Invasive fungal disease in children with acute myeloid leukaemia: An Australian multicentre 10-year review.

Invasive fungal disease (IFD) is a common and important complication in children with acute myeloid leukaemia (AML). We describe the epidemiology of IFD in a large multicentre cohort of children with AML. As part of the retrospective multicentre cohort TERIFIC (The Epidemiology and Risk factors for Invasive Fungal Infections in immunocompromised Children) study, proven/probable/possible IFD episodes occurring in children with primary or relapsed/refractory AML from 2003 to 2014 were analysed. Crude IFD prevalence, clinical characteristics, microbiology and treatment were assessed. Kaplan-Meier survival analysis was used to estimate 6-month survival. There were 66 IFD episodes diagnosed in 63 children with AML. The majority (75.8%) of episodes occurred in the context of primary AML therapy. During primary AML therapy, the overall prevalence was 20.7% (95% CI 15.7%-26.5%) for proven/probable/possible IFD and 10.3% (95% CI 6.7%-15.0%) for proven/probable IFD. Of primary AML patients, 8.2% had IFD diagnosed during the first cycle of chemotherapy. Amongst pathogens implicated in proven/probable IFD episodes, 74.4% were moulds, over a third (37.9%) of which were non-Aspergillus spp. Antifungal prophylaxis preceded 89.4% of IFD episodes, most commonly using fluconazole (50% of IFD episodes). All-cause mortality at 6months from IFD diagnosis was 16.7% with IFD-related mortality of 7.6% (all in cases of proven IFD). IFD is a common and serious complication during paediatric AML therapy. Mould infections, including non-Aspergillus spp. predominated in this cohort. A systematic approach to the identification of patients at risk, and a targeted prevention strategy for IFD is needed.

Invasive Fungal Disease Among Pediatric and Adolescent Patients Undergoing Itraconazole Prophylaxis After Hematopoietic Stem Cell Transplantation

Invasive fungal disease (IFD) is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Itraconazole has been used for prevention of IFD, but data related to incidence and associated factors of IFD in pediatric and adolescent patients on itraconazole prophylaxis remain scarce. To identify incidence and risk factors associated with IFD among pediatric and adolescent patients receiving itraconazole prophylaxis after HSCT. Patients younger than 21 years who received itraconazole prophylaxis after HSCT from January 2007 to December 2016 were retrospectively enrolled. Incidence of IFD within 1 year and associated factors were analyzed. All patients received itraconazole during the pre-engraftment period. Of 170 patients, 29 had IFD, with an incidence of 17.1% at 1 year. IFD at 1 year was significantly associated with increased mortality. Of 29 patients with IFD, only 9 developed IFD while on itraconazole prophylaxis (5.3%), all of whom had invasive pulmonary aspergillosis. No invasive candidiasis occurred during itraconazole prophylaxis. Prolonged neutropenia (hazard ratio [HR]=1.08; 95% confidence interval [CI], 1.02-1.13), graft-versus-host disease within 100 days after transplantation (HR=3.17; 95% CI, 1.17-8.57), and using etoposide in preconditioning regimens (HR=21.60; 95% CI, 2.44-190.95) were significantly associated with IFD at 1 year. No patients had to discontinue itraconazole because of its adverse effects. Itraconazole proffered good efficacy for prevention of candidiasis during the pre-engraftment period. Most IFD episodes occurred after the engraftment period when itraconazole had been discontinued. During this period, patients with risk factors require appropriate fungal prophylaxis.

Low rates of invasive fungal disease in patients with multiple myeloma managed with new generation therapies: Results from a multi-centre cohort study.

A multi-centre study to determine the outcomes and risks for invasive fungal disease (IFD) in myeloma (MM) patients treated with second-generation immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies was conducted. Clinical and microbiology records were reviewed to capture patient demographics, disease characteristics, treatment, IFD episodes and outcomes. Categorical and continuous variables between patients with IFD and without IFD were compared using chi-square test, Fisher's exact test and Mann-Whitney rank sum test, respectively, with P-value<.05 considered statistically significant. Five out of 148 (3.4%) MM patients were diagnosed with five episodes of IFI: 3 were proven, 1 probable and 1 possible. Median time from commencement of new generation therapy to IFD diagnosis was 4.0months (Interquartile range [IQR]: 3.4-5.7). In patients with IFD, median cumulative steroid dose over 60days was 1119mg (IQR: 1066-1333mg). None of the patients with IFD had prolonged neutropenia (neutrophil count<0.5 × 109 /L for more than 10days). Common sites of infection were the respiratory tract (40.0%) and bloodstream (40.0%). Cryptococcus neoformans (n=2) and Candida krusei (n=1) were the fungal pathogens isolated in the three proven cases. 30-day mortality rate was 40.0%. Patients with IFD were younger (median 58 versus 68years, P=.52) and treated with more lines of therapy (median 5 vs 3, P=.04). IFD rate is low in heavily treated MM patients treated with second-generation therapy including monoclonal antibodies. Patients do not appear to have traditional risk factors such as prolonged neutropenia.

Clinical features in proven and probable invasive fungal disease in children and adolescents at a pediatric referral center: a 5-year experience.

There is limited information concerning the overall epidemiology of invasive fungal disease (IFD) in children. The aim of this study was to clarify the clinical features of IFD in a tertiary pediatric care hospital. Patients diagnosed with proven or probable IFD at our hospital between 2011 and 2015 were retrospectively reviewed. Proven and probable IFD were defined according to the European Organization for Research and Treatment of Cancer/Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group consensus. Patients with possible IFD were excluded. The incidence of proven or probable IFD was 26 of 20,079 hospitalized patients (0.13%). The predominant underlying disease was malignancy (54%) and congenital anomaly (27%). The most common diagnosis was candidemia among the patients with proven IFD (8 of 13, 62%). All the isolated pathogens in the candidemia patients were non-albicans Candida spp. The most common site of infection was the lungs in patients with probable IFD (11 of 13 patients, 85%). In probable IFD episodes, positive β-D-glucan and galactomannan were found in 12 of 13 (92%) and 5 of 13 (38%) patients, respectively. All but one patient (96%) received empirical antifungal therapy. No patients underwent surgical resection of residual lesions. The overall mortality was 23% and the attributable mortality of IFD was 12%. Our results suggest the emergence of non-albicans Candida species as important pathogens in childhood IFD.

Invasive fungal disease in patients undergoing umbilical cord blood transplantation after myeloablative conditioning regimen.

Characteristics and risk factors (RFs) of invasive fungal disease (IFD) have been little studied in the setting of umbilical cord blood transplantation (UCBT). We retrospectively included 205 single-unit myeloablative UCBT recipients with a median follow-up of 64months. Fifty-six episodes of IFD were observed in 48 patients (23%) at a median time of 123days after stem cell infusion. Invasive mold disease (IMD) occurred in 42 cases, 38 of them (90%) caused by invasive aspergillosis whereas invasive yeast disease (IYD) occurred in 14 cases, most of them due to candidemia (n=12, 86%). The 5-year cumulative incidence of IFD, IMDs, and IYDs was 24% 19%, and 7%, respectively. In multivariate analysis, three RFs for IMDs were identified: age >30years (HR 3.5, P=0.017), acute grade II-IV graft-versus-host disease (HR 2.3, P=0.011), and ≥1 previous transplant (HR 3.1, P=0.012). The probability of IMDs was 2.5%, 14%, and 33% for recipients with none, 1, or 2-3 RFs, respectively (P<0.001). Among IFD, IMDs had a negative effect on non-relapse mortality in multivariate analysis (HR 1.6, P=0.039). IMDs showed a negative impacton overallsurvival (HR 1.59, P=0.018). Invasive mold disease were very common and serious complication after UCBT.

Infectious complications in children treated for hodgkin and non-hodgkin lymphomas in polish pediatric leukemia/lymphoma study group: incidence, epidemiology and etiology

The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial (BI), viral (VI), and invasive fungal disease (IFD) in patients treated for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) between the years 2013–2015. In the analyzed period of time, within the studied group of 328 children diagnosed and treated for lymphomas, at least one infectious complication (IC) was diagnosed i.e. 39.3% children. In these patients there were 350 episodes of IC, therein 80.6% episodes of BI, 11.1% episodes of VI, and 8.3% episodes of IFD. In both groups, NHL and HL patients, a stable level of bacterial infections, with an increase in resistance rates, and increased levels of viral and fungal infections were observed. Profile of BI does not depend on lymphoma type, with predominance of Gram-negative bacteria and higher prevalence of MDR pathogens. The overall survival of lymphoma patients with IC was comparable for different types of infections.

Epidemiology and Clinical Features of Invasive Fungal Disease in a US Healthcare Network

Background A better understanding of the epidemiology and clinical features of invasive fungal disease (IFD) is integral to improving outcomes. Here we aimed to describe the incidence, clinical features and outcomes of IFD in a large US healthcare network.Methods We developed a novel method of IFD cohort discovery to query all available records in the Intermountain Healthcare electronic data warehouse from 2006 to 2015 for clinical data associated with IFD (Figure 1). Resulting data were overlaid in 124 different combinations to identify high-probability IFD cases. The cohort was manually reviewed and exclusions applied. EORTC/MSG definitions were adapted to categorize IFD in a broad patient population. Linear regression was used to model variation in incidence over time.Results3,391 IFD episodes occurred in 3,171 patients. Mean incidence was 27.4 cases/100,000 patients per year (Figure 2). Estimated mean annual increase was 0.24 cases/100,000 patients (r2 = 0.09, P = 0.21). Candidiasis was most common (56%). Dimorphic fungi, primarily Coccidioides, comprised 24%, followed by aspergillosis (9%). Mean age was 50 years; pediatric cases accounted for 13%. 19.2% of patients had an active malignancy or primary immunodeficiency, 6.9% were transplant recipients, and 27.5% were on immunosuppression. Lymphopenia preceded IFD in 24.4% of patients. Hospital admission occurred in 75%; median length of stay was 12 days. All-cause mortality was 17% at 42 days and 28.6% at 1 year. 42-day mortality was highest in aspergillosis (27.5%), 20.5% for Candida, and lowest for dimorphic fungi (7.5%).Conclusion In this population, IFD was not uncommon, affected a broad spectrum of patients and had high observed mortality.Table 1: N % IFD episodes3391100Proven225966.6Probable86825.6Possible2647.8Age (mean, SD)50 (23.8)Male174451.4Charlson score (median, IQI)3 (1, 6)Any malignancy46113.6Leukemia/lymphoma2116.2Allogeneic BMT1063.1Autologous BMT160.5Solid organ transplant792.3Other (HIV, etc.)55116.2IS medication93227.5Lymphopenia82824.4Neutropenia2587.6Hospitalization252974.6Length of stay, days (median, IQI)12 (5, 26)42-day mortality57517.01-year mortality97128.6BMT-bone marrow transplant; IS-immunosuppressiveFigure 1.Cohort discovery flowchart.Figure 2.Trends in invasive fungal disease incidence.Disclosures B. Webb, Astellas Pharma Global Development, Inc.: Grant Investigator, Research grant. J. Ferraro, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. S. Rea, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. J. Kammerer, Astellas Pharma Global Development, Inc..: Employee, Salary. S. Kaufusi, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. B. Goodman, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. G. Martin, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. J. Spalding, Astellas Pharma Global Development, Inc.: Employee, Salary

Invasive Fungal Disease in Pediatric Solid Organ Transplant Recipients.

Solid organ transplant (SOT) recipients are at risk for invasive fungal disease (IFD). Data on IFD burden in pediatric patients are limited. We aimed to determine the incidence and outcome of IFD in a large cohort of pediatric patients who underwent SOT. A single-center cohort of pediatric patients who underwent SOT between 2000 and 2013 was assembled retrospectively. The patients were followed for 180 days after transplant or until death to determine the presence or absence of IFD. The 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group criteria were used to define IFD as proven or probable. The incidence of IFD, all-cause mortality rate, and case-fatality rate at 180 days were calculated. Among 584 pediatric patients who underwent SOT, 13 patients sustained 14 episodes of IFD (candidiasis, aspergillosis, and mucormycosis). The overall incidence was 2.2% (14.3 IFD events per 100000 patient-days). The IFD rates according to transplant type were 12.5% (1 of 8) (heart/lung), 11.4% (4 of 35) (lung), 4.7% (8 of 172) (liver), 0% (0 of 234) (kidney), and 0% (0 of 135) (heart). Three patients with IFD (2 lung and 1 heart/lung) died, and all these deaths were deemed likely attributable to the IFD; the case-fatality rate was 21.4% (3 of 14). The overall incidence of IFD in these pediatric SOT recipients was low but varied across transplant type, with heart/lung and lung recipients having the highest IFD rate. Given the attributable case-fatality rate, the risk of death resulting from IFD is potentially high. More data on groups at higher risk, such as lung transplant recipients, are needed to guide targeted antifungal prophylaxis.

Impact of risk stratification on the duration of caspofungin therapy for invasive fungal disease in acute leukemic patients.

We retrospectively analyzed 141 acute leukemia patients with unclassified invasive fungal disease episodes during chemotherapy to determine the optimum duration of antifungal treatment. Patients were divided into standard-risk and high-risk groups and treated with intravenous caspofungin for either 1 or 2 weeks, followed by oral voriconazole. Favorable responses occurred in 75.9% of patients (107/141) overall. Although there were no significant differences in response rates between patients receiving 1 or 2 weeks in the standard-risk group (p = 0.12 and p = 0.19, respectively), in the high-risk group, response rates were significantly higher in the 2-week than the 1-week treatment group (p = 0.01 and p = 0.02, respectively). The duration of caspofungin treatment for patients with unclassified invasive fungal diseases may be optimized by risk stratification.

A prospective feasibility study of primary prophylaxis against invasive fungal disease with voriconazole following umbilical cord blood transplantation with fludarabine-based conditioning

Despite the recent introduction of a new class of anti-Aspergillus agents, no standard regimen for the prevention of invasive fungal disease (IFD) following allogeneic hematopoietic stem cell transplantation has been shown to be superior to fluconazole. The present prospective, single-arm study investigated the feasibility of voriconazole (VOR) administration as primary prophylaxis in 52 recipients of umbilical cord blood transplantation (CBT) with fludarabine-based conditioning, who had no previous IFD episodes. Proven or probable IFD was determined using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group, and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria were considered as breakthrough infections. VOR was administered as prophylaxis for a total of 6884 patient-days following CBT. The mean duration of VOR administration after transplantation was 132 days (range, 1-769); 44 patients (85 %) had advanced disease, 15 (29 %) had a history of allogeneic HSCT, and 29 (56 %) received systemic corticosteroid therapy for allogeneic immune-mediated complications. Under the prophylaxis with VOR, one patient developed probable invasive aspergillosis on day 71, and the cumulative incidence of IFD was 4.5 % at day 180. None of the patients developed breakthrough candida or zygomycetes infections. Under the extensive therapeutic dose monitoring, VOR was safely administered with a calcineurin inhibitor and was well tolerated. These results suggest that VOR represents a feasible primary prophylactic agent for IFD after CBT with fludarabine-based conditioning.

Risk Factors for Invasive Fungal Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Single Center Experience

Invasive fungal disease (IFD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HCT). We performed a retrospective review of 271 adults with a hematologic malignancy undergoing allogeneic HCT to determine the incidence of and risk factors for IFD and to examine the impact of IFD on nonrelapse mortality and overall survival. We defined IFD using standard criteria and selected proven and probable cases for analysis. Diagnoses in the study group included acute leukemia (42%), non-Hodgkin lymphoma (24%), myelodysplastic syndrome (15%), chronic lymphocytic leukemia (5%), and other hematologic disorders (14%). Conditioning included reduced-intensity (64%) and myeloablative (36%) regimens. Donor sources were HLA-matched sibling (60%), matched unrelated (20%), haploidentical (12%), and cord blood (8%). A total of 51 episodes of IFD were observed in 42 subjects (15%). Aspergillus spp (47%) was the most frequent causative organism, followed by Candida spp (43%). The majority of IFD cases (67%) were reported after day +100 post-HCT. In multivariate analysis, haploidentical donor transplantation (hazard ratio [HR], 3.82; 95% confidence interval [CI], 1.49-9.77; P = .005) and grade II-IV acute graft-versus-host disease (HR, 2.55; 95% CI, 1.07-6.10; P = .03) were risk factors for the development of IFD. Conversely, higher infused CD34+ cell dose was associated with a lower risk of IFD (HR, 0.80; 95% CI, 0.68-0.94; P = .006, per 1 × 106 cells/kg increase in CD34+ cell infusion). IFD-related mortality was 33.3%. Nonrelapse mortality was significantly higher in patients who developed IFD compared with those without IFD (P < .001, log-rank test). Patients with IFD had lower overall survival (5.8 months versus 76.1 months; P < .001, log-rank test). Further studies exploring strategies to increase the infused cell dose and determine adequate prophylaxis, especially against aspergillus, beyond day +100 are needed.

Indications and outcomes of antifungal therapy in French patients with haematological conditions or recipients of haematopoietic stem cell transplantation

Invasive fungal disease (IFD) remains a major concern in patients with haematological conditions. We describe diagnoses, therapeutic management and outcomes in unselected consecutive patients from haematological facilities treated for suspected or documented IFD. In this observational prospective study, children/adults with haematological conditions or haematopoietic stem cell transplantation (HSCT) were recruited upon start of non-prophylactic systemic antifungal treatment in 37 French haematological facilities (December 2007 to December 2008). IFD episodes were classified according to the 2008 EORTC/MSG criteria. The cohort included 419 patients (298 adults and 121 children): 88% haematological malignancies, 28% HSCT recipients and 68% neutropenic. Patients had 423 IFD episodes: 21% mycologically documented (59% probable/proven aspergillosis, 32% proven candidiasis and 9% probable/proven other IFD) and 20% classified as possible IFD. The remaining cases were assigned to two groups: febrile neutropenia (34%) and unclassified (25%), 9% of which were classified as possible/probable/proven IFD by day 7. Treatment was thus initiated early in 59% of patients; liposomal amphotericin B and caspofungin were the most common single-agent therapies. The 12 week mortality was 18% for probable/proven aspergillosis, 15% for proven candidiasis, 10% for probable/proven other IFD, 9% for possible IFD, 3% for febrile neutropenia and 12% for unclassified episodes (log rank P = 0.016); it was dependent on age, complete remission of underlying haematological disease and mechanical ventilation. In this comprehensive sample of haematological patients receiving antifungal treatment, we observe a widespread resort to early therapy and a low mortality rate, including in patients with probable or proven IFD.

Efficacy of caspofungin and itraconazole as secondary antifungal prophylaxis: analysis of data from a multinational case registry

Patients surviving invasive fungal disease (IFD) and needing further antineoplastic chemotherapy are at high risk of recurrent fungal infection. In the absence of randomised controlled trials in this area, secondary prophylactic regimens are diverse. From 448 patients registered with the Multinational Case Registry of Secondary Antifungal Prophylaxis, we performed an analysis of patients receiving caspofungin (CAS) or itraconazole (ITC). All patients had an underlying haematological malignancy and had been diagnosed with an episode of IFD earlier in their course of treatment. Data collected comprised demographics, underlying disease, first episode of IFD, antifungal prophylaxis, incidence and outcome of breakthrough IFD and survival. A total of 75 patients were evaluated, comprising 28 receiving CAS and 47 receiving ITC. Patients in the CAS group were more likely to have had progression of underlying disease (32.1% vs. 8.5%; P = 0.028) as well as incomplete response of initial IFD at baseline (85.7% vs. 57.4%; P = 0.005). Allogeneic stem cell transplantation was more prevalent in patients receiving CAS (46.4% vs. 14.9%; P = 0.010). There was no difference in the occurrence of breakthrough IFD between both groups (32.1% vs. 31.9%). Treatment outcomes for recurrent IFD and overall mortality did not differ between groups. Both ITC and CAS were equally effective in preventing second episodes of IFD. Patients with uncontrolled first IFD, uncontrolled underlying disease or those receiving stem cell transplantation were more likely to have received CAS prophylaxis. Despite antifungal prophylaxis, risk of breakthrough IFD was high in both groups.

Enfermedad fúngica invasora en pacientes hemato-oncológicos y receptores de trasplante de precursores hematopoyéticos bajo la perspectiva de los criterios diagnósticos EORTC/MSG

Invasive fungal disease (IFD) is a severe complication occurring mostly in haematooncological (H-O) patients and hematopoietic stem cell transplant (HSCT) receptors. Our aim was to describe the IFD occurring in our H-O and HSCT patients according to the EORTC/MSG revised criteria.IFD surveillance was performed in adult patients of the Hospital Clínico Universidad Catolica, Santiago, Chile, from January 2004 to January 2008.A total of 41 IFD episodes were identified in 39 patients; mean age was 46.6 +/- 9.9 years, and 87.8% and 12.2% occurred in H-O and HCTS patients respectively. 15/41(36.6%) episodes were proven, 36.6% probable and 11/41 (26.8%) possible. In 26 (63.4%) episodes aspergillosis was diagnosed (20 pulmonary, 3 sinus, 1 laryngeal and 1 case with pulmonary and cerebral involvement). In 7 patients (17.1%) candidiasis was diagnosed, 5 with a proven bloodstream infection and 2 with possible hepatosplenic candidiasis; mucormyeosis was diagnosed in 4 (9.8%) Fusarium infection was demonstrated in 2 patients (4.9%), and Mucor and Aspergillus pulmonary coinfection and Alternaria sp rhino-sinusitis in one patient each. The frequency of IFD among febrile neutropenic patients was 26.2% and 6.4% in H-O and HSCT receptors respectively. The overall mortality was 36%.Aspergillosis is the most common IFD infection among H-O patients and HSCT receptors in our center. Candidiasis followed although only in H-O patients most probably because of routine use of antifungal prophylaxis in HSCT recipients. Continuous surveillance is required to develop local guidelines and to evaluate antifungal strategies in different clinical scenarios.

Invasive fungal disease in hemato-oncological and hematopoietic stem cell transplantation patients from Hospital Clinico Universidad Católica, Santiago-Chile using revised EORTC/MSG diagnostic criteria

Invasive fungal disease (IFD) is a severe complication occurring mostly in haematooncological (H-O) patients and hematopoietic stem cell transplant (HSCT) receptors. Our aim was to describe the IFD occurring in our H-O and HSCT patients according to the EORTC/MSG revised criteria. IFD surveillance was performed in adult patients of the Hospital Clínico Universidad Catolica, Santiago, Chile, from January 2004 to January 2008. A total of 41 IFD episodes were identified in 39 patients; mean age was 46.6 +/- 9.9 years, and 87.8% and 12.2% occurred in H-O and HCTS patients respectively. 15/41(36.6%) episodes were proven, 36.6% probable and 11/41 (26.8%) possible. In 26 (63.4%) episodes aspergillosis was diagnosed (20 pulmonary, 3 sinus, 1 laryngeal and 1 case with pulmonary and cerebral involvement). In 7 patients (17.1%) candidiasis was diagnosed, 5 with a proven bloodstream infection and 2 with possible hepatosplenic candidiasis; mucormyeosis was diagnosed in 4 (9.8%) Fusarium infection was demonstrated in 2 patients (4.9%), and Mucor and Aspergillus pulmonary coinfection and Alternaria sp rhino-sinusitis in one patient each. The frequency of IFD among febrile neutropenic patients was 26.2% and 6.4% in H-O and HSCT receptors respectively. The overall mortality was 36%. Aspergillosis is the most common IFD infection among H-O patients and HSCT receptors in our center. Candidiasis followed although only in H-O patients most probably because of routine use of antifungal prophylaxis in HSCT recipients. Continuous surveillance is required to develop local guidelines and to evaluate antifungal strategies in different clinical scenarios.