It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or ...special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or ...special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and ...chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.
We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37).
The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval CI, 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse.
We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.).
Changes in antineoplastic treatments and transplant practices are driving shifts in the epidemiology of invasive fungal diseases (IFDs). Patients with acute myelogenous leukemia (AML) and those ...undergoing bone marrow transplant (BMT) are at greatest risk for contracting IFDs. Unfortunately, there are few large population studies that can be used to track trends and help us to better understand why certain individuals within recognized high-risk groups are at greater risks than others for contracting IFDs. The growing use of antifungals in prophylaxis and treatment influences which species will cause an IFD as well as the resistance patterns of these fungi. On the one hand, antifungal prophylaxis has mitigated, but not eliminated, the threat of candidiasis. Furthermore, prophylaxis trials have shown trends of reduced aspergillosis in BMT patients; however, no survival benefits were seen, and 1 trial indicated a lower rate of aspergillosis and survival benefits in patients with AML. Future prophylaxis trials should reduce the heterogeneity of risk in study participants in order to better assess benefit; these trials should also incorporate fungal biomarkers into their design. The threat of emerging fungal resistance in prophylaxis strategies is real and must be monitored.
Background.Computed tomography (CT) of the chest may be used to identify the halo sign, a macronodule surrounded by a perimeter of ground-glass opacity, which is an early sign of invasive pulmonary ...aspergillosis (IPA). This study analyzed chest CT findings at presentation from a large series of patients with IPA, to assess the prevalence of these imaging findings and to evaluate the clinical utility of the halo sign for early identification of this potentially life-threatening infection. Methods.Baseline chest CT imaging findings from 235 patients with IPA who participated in a previously published study were systematically analyzed. To evaluate the clinical utility of the halo sign for the early identification and treatment of IPA, we compared response to treatment and survival after 12 weeks of treatment in 143 patients who presented with a halo sign and in 79 patients with other imaging findings. Results.At presentation, most patients (94%) had ⩾1 macronodules, and many (61%) also had halo signs. Other imaging findings at presentation, including consolidations (30%), infarct-shaped nodules (27%), cavitary lesions (20%), and air-crescent signs (10%), were less common. Patients presenting with a halo sign had significantly better responses to treatment (52% vs. 29%; P < .001) and greater survival to 84 days (71% vs. 53%; P < .01) than did patients who presented with other imaging findings. Conclusions.Most patients presented with a halo sign and/or a macronodule in this large imaging study of IPA. Initiation of antifungal treatment on the basis of the identification of a halo sign by chest CT is associated with a significantly better response to treatment and improved survival.
Background. Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical ...studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. Methods. After the introduction of the original 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) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. Results. The revised definitions retain the original classifications of “proven,” “probable,” and “possible” invasive fungal disease, but the definition of “probable” has been expanded, whereas the scope of the category “possible” has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. Conclusions. These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in ...establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.
Allogeneic hematopoietic cell transplantation (HCT) is curative but is associated with life-threatening complications. Most deaths occur within the first 2 years after transplantation. In this ...report, we examine long-term survival in 2-year survivors in the largest cohort ever studied.
Records of 10,632 patients worldwide reported to the Center for International Blood and Marrow Transplant Research who were alive and disease free 2 years after receiving a myeloablative allogeneic HCT before 2004 for acute myelogenous or lymphoblastic leukemia, myelodysplastic syndrome, lymphoma, or severe aplastic anemia were reviewed.
Median follow-up was 9 years, and 3,788 patients had been observed for 10 or more years. The probability of being alive 10 years after HCT was 85%. The chief risk factors for late death included older age and chronic graft-versus-host disease (GVHD). For patients who underwent transplantation for malignancy, relapse was the most common cause of death. The greatest risk factor for late relapse was advanced disease at transplantation. Principal risk factors for nonrelapse deaths were older age and GVHD. When compared with age, sex, and nationality-matched general population, late deaths remained higher than expected for each disease, with the possible exception of lymphoma, although the relative risk generally receded over time.
The prospect for long-term survival is excellent for 2-year survivors of allogeneic HCT. However, life expectancy remains lower than expected. Performance of HCT earlier in the course of disease, control of GVHD, enhancement of immune reconstitution, less toxic regimens, and prevention and early treatment of late complications are needed.
Aspergillus fumigatus is an opportunistic mold that infects patients who are immunocompromised or have chronic lung disease, causing significant morbidity and mortality in these populations. While ...the factors governing the host response to A. fumigatus remain poorly defined, neutrophil recruitment to the site of infection is critical to clear the fungus. Galectin-3 is a mammalian beta-galactose-binding lectin with both antimicrobial and immunomodulatory activities, however the role of galectin-3 in the defense against molds has not been studied. Here we show that galectin-3 expression is markedly up-regulated in mice and humans with pulmonary aspergillosis. Galectin-3 deficient mice displayed increased fungal burden and higher mortality during pulmonary infection. In contrast to previous reports with pathogenic yeast, galectin-3 exhibited no antifungal activity against A. fumigatus in vitro. Galectin-3 deficient mice exhibited fewer neutrophils in their airways during infection, despite normal numbers of total lung neutrophils. Intravital imaging studies confirmed that galectin-3 was required for normal neutrophil migration to the airspaces during fungal infection. Adoptive transfer experiments demonstrated that stromal rather than neutrophil-intrinsic galectin-3 was necessary for normal neutrophil entry into the airspaces. Live cell imaging studies revealed that extracellular galectin-3 directly increases neutrophil motility. Taken together, these data demonstrate that extracellular galectin-3 facilitates recruitment of neutrophils to the site of A. fumigatus infection, and reveals a novel role for galectin-3 in host defense against fungal infections.
Mucormycosis is an aggressive, life-threatening infection caused by fungi in the order Mucorales. The current diagnosis of mucormycosis relies on mycological cultures, radiology and histopathology. ...These methods lack sensitivity and are most definitive later in the course of infection, resulting in the prevention of timely intervention. PCR-based approaches have shown promising potential in rapidly diagnosing mucormycosis. The spore coating protein homolog encoding
genes are uniquely and universally present among Mucorales. Thus,
genes are potential targets for the rapid diagnosis of mucormycosis. We infected mice with different Mucorales known to cause human mucormycosis and investigated whether
could be PCR amplified from biological fluids. Uninfected mice and those with aspergillosis were used to determine the specificity of the assay.
was detected as early as 24 h postinfection in plasma, urine, and bronchoalveolar lavage (BAL) samples from mice infected intratracheally with
,
,
,
, or
but not from samples taken from uninfected mice or mice infected with
Detection of
from urine samples was more reliable than from plasma or BAL fluid. Using the receiver operating characteristic method, the sensitivity and the specificity of the assay were found to be 90 and 100%, respectively. Finally,
was PCR amplified from urine samples of patients with proven mucormycosis. Thus, PCR amplification of
is a promising target for the development of a reliable, sensitive, and simple method of early diagnosis of mucormycosis.
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