Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the incidence, risk factors, and outcome of Aspergillus infections among marrow transplant recipients, records from 2496 patients were reviewed, and 214 patients had Aspergillus organisms identified. Of these, 158 had invasive aspergillosis, 44 were colonized, and 12 had contaminated cultures. The incidence of invasive aspergillosis increased from 5.7% to 11.2% during the study. The onset of infection was bimodal, peaking 16 and 96 days after transplant. For patients within 40 days after transplant, underlying disease, donor type, season, and transplant outside of laminar air flow rooms were associated with significant risk for invasive aspergillosis. For patients >40 days after transplant, age, underlying disease, donor type, graft-versus-host disease, neutropenia, and corticosteroid use were associated with increased risk of aspergillosis. Only 31% of infected patients were neutropenic at the time of diagnosis. The risk factors for aspergillosis depend on the time after marrow transplant and include both host and environmental characteristics.
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PMID:Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation. 960 75

This study retrospectively reviews infections over a 7-year period in 60 consecutive adults (median age 25 years) undergoing their first unrelated donor bone marrow transplant (UD-BMT). T-cell depletion was employed in 93%. More than half the patients had one or more severe, potentially life-threatening, infections. There was a high incidence of invasive fungal infections (Aspergillus 17, Candida four), despite the use of itraconazole or amphotericin prophylaxis. Ten Aspergillus infections occurred beyond 100 d. Two patients (11%) with invasive aspergillosis survived. Clustering of infections was noted, with invasive fungal infections significantly associated with bacteraemias (OR 3.73, P=0.06) and multiple viral infections (OR 4.25, P=0.05). There were 21 severe viral infections in 16 patients, with CMV disease occurring in four patients only; viral pneumonitis was predominantly due to 'community respiratory' viruses. Most early bacteraemias (68%) were due to Gram-positive organisms. The majority of episodes of Gram-negative sepsis were caused by non-fastidious non-fermentative bacteria, such as Pseudomonas spp. and Acinetobacter spp., historically regarded as organisms of low pathogenicity. In patients with successful engraftment and minimal graft-versus-host disease, late infections suggestive of continued immune dysfunction (shingles, recurrent lower respiratory infections, Salmonella enteritis and extensive warts) were common.
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PMID:Infections in adults undergoing unrelated donor bone marrow transplantation. 1008 95

Patients receiving allogeneic bone marrow transplants are at risk of developing Aspergillus infections. The pre-transplant risk factors for the development of invasive disease include prolonged neutropenia, colonization with Aspergillus sp. or a prior history of fungal infection. Post-transplant risk factors include severe graft-versus-host disease with concomitant high-dose corticosteroid therapy, and colonization with Aspergillus sp. The antifungal prophylaxis of selected high-risk pre-transplant patients at the Royal Melbourne Hospital includes granulocyte transfusions and AmBisome. In high-risk patients post-engraftment, prophylaxis consists of oral itraconazole, or if it cannot be tolerated, AmBisome. Antifungal prophylaxis is discontinued upon resolution of neutropenia, when prednisolone dose falls below 10 mg/day or when Aspergillus colonization disappears. Following this regimen, there has been only one death due to fungal infection in over 80 consecutive allograft patients. This patient was infected with an amphotericin B-resistant organism.
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PMID:Prophylaxis and treatment of patients with aspergillosis: an overview, including the Royal Melbourne Hospital experience. 1180 86

Invasive aspergillosis (IA) is common in allogeneic SCT recipients, with an incidence of 4-10%. The majority of these infections are diagnosed several months after SCT and they are frequently associated with GVHD. The diagnosis is difficult and often delayed. Established IA is notoriously difficult to treat with a death rate of 80-90%. This review summarises recent data on this problem to assess whether there has been any progress. Effective prophylactic measures are still lacking. Severe immunosuppression is the main obstacle to the success of therapy. Recent and ongoing developments in diagnostic measures and new antifungal agents may improve treatment results to some extent, but Aspergillus infections still remain a formidable problem in allogeneic transplantation. Further studies in this field will focus on the role of various cytokines and combinations of antifungal agents.
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PMID:Aspergillus infections in allogeneic stem cell transplant recipients: have we made any progress? 1247 86

Invasive aspergillosis is an increasingly common and often fatal opportunistic fungal infection in patients with hematologic malignancies. Prolonged and profound neutropenia remains a key risk factor for the development of invasive aspergillosis. However, qualitative deficiencies in host immune responses resulting from prolonged corticosteroid therapy, graft-versus-host disease, and cytomegalovirus infection are important risk factors for the recurrence and progression of Aspergillus infections after bone marrow recovery. Early diagnosis of invasive aspergillosis remains a challenge, and few tools are available for monitoring its course once the diagnosis is established. Even with the recent introduction of new antifungal therapies, mortality in patients with invasive aspergillosis remains high, and uniformly effective prophylaxis or preemptive therapeutic strategies are lacking. Strategies such as combination antifungal therapy and immunotherapy often are used as first-line treatment approaches in patients with documented invasive aspergillosis despite a paucity of clinical trial data. Recent advances in our understanding of the epidemiology, pathogenesis, and treatment of invasive aspergillosis in patients with hematologic malignancies are reviewed. The problems and controversies associated with defining optimal treatment strategies for invasive aspergillosis in this heavily immunocompromised population are highlighted.
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PMID:Invasive aspergillosis in patients with hematologic malignancies. 1469 39

Invasive fungal infections pose major management problems for clinicians caring for hematopoietic cell transplant patients. Two major fungal genera, Candida and Aspergillus, account for most fungal infections. Rates of systemic Candida infection range from 15% to 25%, mostly in the pre-engraftment period. Prophylaxis by fluconazole has dramatically reduced the frequency of early Candida infections. Caspofungin has recently been shown to offer an excellent alternative to amphotericin B (with less toxicity) or fluconazole (with a broader spectrum) for therapy of systemic Candida infections. Aspergillus infections occur in 15% to 20% of allogeneic hematopoietic cell transplant patients, most frequently in the post-engraftment period; they are associated with a severe diminution of cell-mediated immune responses by graft-versus-host disease and prolonged corticosteroid use. Voriconazole, a recently introduced broad-spectrum azole, has excellent activity against Aspergillus and is generally well tolerated. Voriconazole currently offers the best prospect for success and tolerance as a first-line treatment for aspergillosis. Second-line therapies include lipid formulations of amphotericin B, caspofungin, or intravenous itraconazole. Unfortunately, early initiation of therapy for aspergillosis is frequently not possible because of inaccurate diagnostics. One new diagnostic, the galactomannan assay, has recently been approved, and others are in development; these offer promise for earlier diagnosis without the need for invasive procedures. It is hoped that these new therapies and new diagnostics will usher in a new era of antifungal therapy.
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PMID:A new era of antifungal therapy. 1475 74

Invasive fungal infections (IFI) are common in allogeneic SCT recipients. We have reviewed our experience of IFI with special reference to candidaemia in 685 adult patients transplanted in 1983-2002. The donor was a matched sibling in 505 patients and an unrelated donor in 180 patients. A BM graft was used in 561 patients and a PB graft in 124 patients. Fluconazole prophylaxis was not used during the study period. Definite or probable IFI was observed in 60 patients (8.7%) with a dominance of Aspergillus infections (46 patients, incidence 6.7%). Candidaemia was found only in nine patients (1.3%). The causative agents were Candida albicans (n=8), C. krusei (n=2), and C. glabrata (n=1); in two patients, two causative agents were found. The median time to the diagnosis of candidaemia was 53 days (range 6-249 days) post transplant. Seven patients were neutropaenic at diagnosis, and four patients had experienced acute GVHD. All patients received antifungal therapy, but only one patient was cured. According to this study, candidaemia was a rare event in allogeneic SCT recipients. Thus, systematic prophylaxis against Candida infections might not be indicated. The prognosis of established infections is still poor due to comorbid conditions, notably GVHD.
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PMID:Candidaemia in allogeneic stem cell transplant recipients: low risk without fluconazole prophylaxis. 1551 9

Tens of thousands of patients undergo hematopoietic stem cell transplantation (HSCT) annually, 15 to 40% of whom are admitted to the intensive care unit. Pulmonary complications are the most life threatening conditions that develop in HSCT recipients. Both infectious and noninfectious complications occur more frequently in allogeneic HSCT. The management of HSCT recipients requires knowledge of their immune status, appropriate diagnostic evaluation, and early treatment. During the pre-engraftment phase (0 to 30 days after transplant), the most prevalent pathogens causing infection are bacteria and Candida species and, if the neutropenia persists, Aspergillus species. The early post-engraftment phase (30 to 100 days) is characterized by cytomegalovirus (CMV), Pneumocystis jiroveci, and Aspergillus infections. During the late posttransplant phase (> 100 days), allogeneic HSCT recipients are at risk for CMV, community-acquired respiratory virus, and encapsulated bacterial infections. Antigen and polymerase chain reaction assays are important for the diagnosis of CMV and Aspergillus infections. Diffuse alveolar hemorrhage (DAH) and peri-engraftment respiratory distress syndrome occur in both allogeneic and autologous HSCT recipients, usually during the first 30 days. Bronchiolitis obliterans occurs exclusively in allogeneic HSCT recipients with graft versus host disease. Idiopathic pneumonia syndrome occurs at any time following transplant. Bronchoscopy is usually helpful for the diagnosis of the infectious pulmonary complications and DAH.
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PMID:Major complications following hematopoietic stem cell transplantation. 1679 62

Aspergillus infections are a threat to in patients with hematological malignancies. Known risk factors are profound and long lasting neutropenia, uncontrolled graft versus host disease, continuous administration of steroids and environmental factors such as hospital construction. Numerous efforts have been undertaken for prophylaxis of invasive aspergillosis in high-risk populations. Most of them failed to demonstrate survival advantages. Prophylaxis makes sense, since diagnosis and treatment of invasive aspergillosis remain difficult. The introduction of non-culture based tools for the diagnosis of invasive aspergillosis is an important step forward for early and sensitive diagnosis of invasive aspergillosis. Early treatment is the cornerstone of a successful management of invasive aspergillosis. Substantial improvement came with the introduction of lipid formulations of amphotericin B in the early 1990s. Voriconazole was the first azole that improved the overall survival for patients with invasive aspergillosis. Newer azoles and the echinocandins were introduced for the treatment of invasive aspergillosis in the late 1990s. Voriconazole and liposomal amphotericin B allow a safer and more effective treatment of invasive aspergillosis when compared with amphotericin B-desoxycholate. Combination of antifungal agents has been introduced in clinical trials. Up to now no significant benefit has been obtained with antifungal combination compared to voriconazole alone. Because mortality of invasive aspergillosis remains up to more than 50%, prophylaxis, early diagnosis and early initiation of antifungal therapy are of utmost importance for the reduction of invasive aspergillosis related mortality. Despite all advances in the management of invasive aspergillosis important questions remain unresolved. This article reviews the current state and new insights in the management of invasive aspergillosis and points out clinicians unmet needs.
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PMID:Invasive aspergillosis: new insights into disease, diagnostic and treatment. 2327 38