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)

A 59-year-old man was admitted to our hospital with a diagnosis of acute myeloid leukemia in September 2004. He developed invasive pulmonary aspergillosis (IPA) and candidiasis, which were improved by administration of micafungin and amphotericin B (AMPH-B). He received reduced-intensity unrelated cord-blood transplantation without induction chemotherapy. He developed grade IV graft-versus-host disease (GVHD) and the administration of steroids against GVHD was prolonged. Voriconazole (VRCZ) was used for a long period to prevent recurrence of the IPA. Afterwards, infiltrates in the bilateral upper lung fields were detected on a chest CT scan, and a diagnosis of pulmonary mucormycosis was made following detection of Mucor circinelloides from the patient's sputum culture. He then began receiving AMPH-B but died of massive hemoptysis. Mucormycosis usually occurs in immunocompromised hosts such as neutropenic patients with hematologic diseases and is a fatal fungal infection characterized by a rapid and progressive clinical course. Some overseas investigators have recently reported that VRCZ prophylaxis may result in breakthrough mucormycosis in hematopoietic stem cell transplant recipients. These findings suggest that it is very important to pay attention to mucormycosis in hematopoietic stem cell transplant recipients in this country.
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PMID:[Breakthrough pulmonary mucormycosis during voriconazole treatment after reduced-intensity cord blood transplantation for a patient with acute myeloid leukemia]. 1757 88

Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.
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PMID:Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases. 1758 Feb 55

The risk of recurrence or progression of prior invasive fungal infection, predominantly due to molds, is 11-33% during subsequent stem cell transplantations or myelosuppressive chemotherapy, with a high mortality. Risk factors at the time of transplant include active infection and having received <6 weeks of antifungal therapy, while after transplant prolonged neutropenia and graft-versus-host disease requiring aggressive immunosuppression are important. The use of peripheral blood stem cells has been associated with a lower risk. Minimal data are available regarding the role of preventative strategies such as surgical resection of pulmonary lesions and prophylactic granulocyte transfusions during neutropenia, the optimal duration of antifungal prophylaxis, and the appropriate monitoring strategy. This article critically evaluates these issues and provides recommendations for the secondary prophylaxis of invasive mold infections.
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PMID:Minimizing the risk of recurrent or progressive invasive mold infections during stem cell transplantation or further intensive chemotherapy. 1760 32

Posaconazole is a new drug in the triazole class that has recently been investigated in pivotal Phase III clinical trials. Its antifungal activity is based on the inhibition of the fungal ergosterol synthesis. As demonstrated in vitro, posaconazole exhibits fungicidal activity against Aspergillus spp., Candida spp. and zygomycetes. Currently, posaconazole is only available as an oral suspension. Food consumption affects the bioavailability of posaconazole, while the exposure to posaconazole increases in a dose-proportional manner with a saturation of absorption occurring with a daily dose over 800 mg. Posaconazole is well tolerated without an increase in risk of any treatment-related adverse events during prolonged treatment for 6 or more months (n = 108). Posaconazole has been recently approved by the US FDA and other regulatory bodies for the treatment of oropharyngeal candidiasis, and the prophylaxis of invasive Aspergillus and Candida infections in severely immunocompromised patients. As demonstrated in two pivotal Phase III trials, posaconazole prophylaxis of invasive fungal infection in patients severely immunocompromised by graft-versus-host disease (n = 600) or neutropenia (n = 602) is superior to fluconazole and/or itraconazole prophylaxis. Significantly more patients who received posaconazole, instead of fluconazole, as treatment for oropharyngeal candidiasis sustained clinical success after the treatment was stopped. Preliminary data from a subgroup analysis (n = 24) of two salvage therapy trials for invasive fungal infections, as well as single case reports and series and in vitro studies, suggest that posaconazole might be an attractive oral treatment alternative for zygomycosis.
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PMID:Posaconazole: a next-generation triazole antifungal. 1766 96

Cord blood-derived stem cells are successfully used in the treatment of cancer and congenital disorders in children. This alternative source of stem cells is also explored for adult cancer patients with limited donor options. However, delayed engraftment, prolonged neutropenia, secondary graft loss, and graft-versus-host disease (GVHD) in recipients of cord blood transplantation (CBT) make opportunistic infections a serious concern. We evaluated the spectrum of infections in adults and children undergoing CBT at our National Cancer Institute-designated comprehensive cancer center. The infection incidence rate ratio (total infection episodes/days at risk [survival after CBT] x 100) was 2.4 times higher in 35 adult patients than in 62 children, especially in adults with neutropenia (3 x higher) and GVHD (1.9 x higher). Ninety-two percent of fungal infection episodes occurred within 100 days after transplantation; half of these infections occurred in the first 30 days after CBT. Most bacterial infections (80%) were also diagnosed in the first 100 days, whereas late (>100 d) post-CBT cytomegalovirus and varicella zoster virus infections occurred only in children with chronic GVHD. Multivariate analysis showed that resolution of lymphocytopenia (> or =1000 cells/microL) (hazard ratio [HR] 0.71; p < 0.0001) and successful engraftment (HR 0.20; p < 0.0001) were associated with a low risk of serious infection. Children (HR 0.36; p < 0.0002) with sustained engraftment (HR 0.39; p < 0.004) and those with cancer in remission (HR 0.47; p < 0.007) were less likely to die from infection. More effective measures for surveillance and prevention of late cytomegalovirus and varicella zoster virus infections in children with CBT and chronic GVHD are needed.
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PMID:Infections in 100 cord blood transplantations: spectrum of early and late posttransplant infections in adult and pediatric patients 1996-2005. 1800 77

Infection is among the leading causes of morbidity and mortality in patients undergoing bone marrow transplantation. Although all infections create difficulties, the most troublesome to those patients are fungal infections. Therapies used to prevent rejection and graft-versus-host disease, as well as an increase in poorly matched or unrelated donors, are believed to contribute to the increase of fungal infections. Mucormycosis, also known as zygomycosis, is an opportunistic fungal infection that is seen rarely in the clinical setting but can be found in patients who are severely neutropenic or immunosuppressed. Oncology nurses caring for bone marrow and peripheral blood stem cell transplantation recipients must know the warning signs of this deadly infection. Early detection and aggressive treatment are patients' best chances of survival.
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PMID:Mucormycosis: a rare but serious infection. 1825 80

Invasive fungal infections (IFIs) are a leading cause of infection-related mortality in patients with acute leukemia and prolonged neutropenia and in allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD). Although invasive candidiasis was the principal IFI predating fluconazole prophylaxis, invasive aspergillosis and other mold infections now cause most deaths from fungal infection in this patient population. The availability of broad-spectrum antifungal agents that can be safely administered over prolonged periods has stimulated interest in using mold-active prophylactic agents early as prophylaxis rather than later as therapy for suspected or documented IFIs. Two recent, prospective, randomized trials have shown a clear benefit of posaconazole prophylaxis in patients with myelodysplastic syndrome and acute mye-logenous leukemia with prolonged neutropenia and in allogeneic HSCT recipients with severe GVHD. In contrast, the peer-reviewed published database on the strategy of preemptive antifungal therapy, in which yeast-active prophylaxis (fluconazole) or no antifungal prophylaxis is used initially and modifications are triggered by a combination of laboratory markers and chest CT scans, is currently limited to an open-label feasibility study. Does sufficient evidence currently exist that the net benefit of the preemptive approach is at least on a par with posaconazole prophylaxis in the specific patient groups that were studied? The authors believe not and that more research is needed before the preemptive strategy can be recommended.
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PMID:Broad-spectrum antifungal prophylaxis in patients with cancer at high risk for invasive mold infections: point. 1831 50

In order to analyze the incidence and high-risk factors of invasive fungal infections among recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), 180 cases of allo-HSCT were enrolled in this study. The incidence and risk factors of IFI were analyzed by method of Kaplan-Meier and Cox regression model. The results showed that an incidence of IFI in 35 cases (19.5%) were detected, with 1 case proven and 34 cases probably diagnosed, which was composed of 18 cases (51.4%) of aspergillosis and 17 cases (48.6%) of candidosis. There was significant difference in one-year overall survival rate between patients with (34.3%) or without (53.8%) IFI. In univariate analysis, risk factors of IFI included: pretransplant fungal infection or colonization, unrelated donor (peripheral blood or bone marrow stem cell) transplantation, acute GVHD, extensive chronic GVHD and the use of methylprednisolone. In multi-variate analysis, the following risk factors of IFI were found:unrelated donor for allogeneic peripheral blood or bone marrow stem cell transplantation, acute GVHD and pretransplant fungal infection or colonization acute GVHD (RR: 2.399, 1.589, and 0.836). It is concluded that IFI is a frequent complication and one of the leading causes of mortality among recipients of allo-HSCT. As for patients with higher risk of IFI, early interventions should be taken.
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PMID:[Invasive fungal infections after allogeneic hematopoietic stem cell transplantation and related risk factors]. 1854 41

Antifungal prophylaxis can be recommended in patients undergoing induction chemotherapy for acute myeloid leukemia and treatment for grade 2 or greater or chronic extensive graft versus host disease. The evidence for prophylaxis is less clear in other clinical settings although certain groups such as patients with prolonged neutropenia after stem cell transplants using bone marrow or cord blood sources and with impaired cell mediated immunity secondary to treatments such as Alemtuzumab are at high risk. The decision to use prophylaxis and which agent to use will be influenced by effectiveness, number needed to treat and the likelihood of toxicity and drug interactions. The availability of rapid diagnostic tests for fungal infection and institutional epidemiology will also influence the need for and choice of prophylaxis. Whilst prophylaxis can be beneficial, it may impede the ability to make a rapid diagnosis of fungal infection by reducing the yield of diagnostic tests and change the epidemiology of fungal infection. As non-culture based diagnostic tests are refined and become more available there may be a shift from prophylaxis to early diagnosis and treatment.
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PMID:Antifungal prophylaxis in adult stem cell transplantation and haematological malignancy. 1858 20

Increasing use of more aggressive treatment approaches in patients with hematologic malignancies leads to an increased frequency of invasive fungal infections, which is a major cause of transplant-related mortality in hematopoietic stem cell recipients. In this respect, the presence of an active fungal infection prior to transplantation may hinder subsequent hematopoietic stem cell transplantation (HSCT); which sometimes is the only curative treatment. We report here the results of 13 consecutive patients transplanted with active fungal infection. Thirteen patients (7 males and 6 females) with a median age of 34 years (range, 16-53 years) underwent 15 HSCT between September 2003 and April 2007. In this group of 15 patients, consisting of hematologic malignancies with high risk of relapse or severe aplastic anemia, 11 (73%) transplants performed in subjects with active invasive fungal infection (IFI) patients survived 30 days after transplantation. Three patients (1 patient with primary disease relapse, 1 patient with graft versus host disease [GVHD] complicated with fungal pneumonia, and 1 patient with severe sinusoidal obstruction syndrome and GVHD complicated with aspiration pneumonia) died on days +66, +74, and +62 posttransplantation, respectively, within the first 100 days of HSCT. After a median follow-up time of 306 days (range, 145-680 days), four of 13 (31%) patients with active IFI were alive and disease free. Among a population of HSCT recipients with a dismal prognosis without transplantation, performing the procedure despite active IFI saved a considerable proportion of the patients. The presence of active IFI did not seem to be an absolute contraindication for HSCT, particularly among high-risk patients in whom a treatment delay could be fatal.
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PMID:Hematopoietic stem cell transplantation in patients with active fungal infection: not a contraindication for transplantation. 1858 55


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