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)

Reports have focused on the emergence of moulds as pathogens in recipients of hematopoietic stem cell transplants. To review the incidence of and risks for mould infections, we examined the records of 5589 patients who underwent hematopoietic stem cell transplantation at the Fred Hutchinson Cancer Research Center (Seattle) from 1985 through 1999. After 1992, the incidence of invasive aspergillosis increased in allograft recipients and remained high through the 1990s. Infections with non-fumigatus Aspergillus species, Fusarium species, and Zygomycetes increased during the late 1990s, especially in patients who received multiple transplants. Although infection caused by Scedosporium species was common in patients who had neutropenia, infection caused by Zygomycetes typically occurred later after transplantation, when patients had graft-versus-host disease. The overall 1-year survival rate was equally poor (similar20%) for all patients with mould infections. The results of the present study demonstrate the changing epidemiology of mould infections, emphasizing the increasing importance of amphotericin B--resistant organisms and the differences in risks and outcome of infection with different filamentous fungi.
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PMID:Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. 1188 Sep 55

Fungal infection is one of the most important causes of morbidity and mortality in bone marrow transplant (BMT) recipients. The growing incidence of these infections is related to several factors including prolonged granulocytopenia, use of broad-spectrum antibiotics, conditioning regimens, and use of immunosuppression to avoid graft-versus-host disease (GvHD). In the present series, we report five cases of invasive mold infections documented among 64 BMT recipients undergoing fluconazole antifungal prophylaxis: 1) A strain of Scedosporium prolificans was isolated from a skin lesion that developed on day +72 after BMT in a chronic myeloid leukemic patient. 2) Invasive pulmonary aspergillosis (Aspergillus fumigatus) was diagnosed on day +29 in a patient with a long period of hospitalization before being transplanted for severe aplastic anemia. 3) A tumoral lung lesion due to Rhizopus arrhizus (zygomycosis) was observed in a transplanted patient who presented severe chronic GvHD. 4) A tumoral lesion due to Aspergillus spp involving the 7th, 8th and 9th right ribs and local soft tissue was diagnosed in a BMT patient on day +110. 5) A patient with a history of Ph1-positive acute lymphocytic leukemia exhibited a cerebral lesion on day +477 after receiving a BMT during an episode of severe chronic GvHD. At that time, blood and spinal fluid cultures yielded Fusarium sp. Opportunistic infections due to fungi other than Candida spp are becoming a major problem among BMT patients receiving systemic antifungal prophylaxis with fluconazole.
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PMID:Fungal infections in marrow transplant recipients under antifungal prophylaxis with fluconazole. 1213 18

We report 4 cases of invasive zygomycosis in hematopoietic stem cell transplant recipients, all occurring after May 2003, when voriconazole began to be used as antifungal prophylaxis. No cases of zygomycosis had been detected in this population in the 3 years prior to May 2003. All 4 patients were receiving immunosuppressive therapy for presumed graft-versus-host disease. Profoundly immunosuppressed patients receiving voriconazole prophylaxis remain at risk for less-common pathogens that are intrinsically resistant to this agent.
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PMID:Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. 1535 28

Hematopoietic stem cell transplantation is used to treat hematologic disorders and as an adjunct treatment for solid organ malignancies. After undergoing transplantation, patients are at risk for opportunistic infections and other complications caused by dysfunction of the immune system. Pulmonary complications include cryptogenic organizing pneumonia, opportunistic pneumonias caused by Aspergillus and Zygomycetes species and cytomegalovirus, alveolar hemorrhage, and constrictive bronchiolitis. Abdominal complications include hepatic veno-occlusive disease, graft-versus-host disease (GVHD), colitis, and hemorrhagic cystitis. Allogeneic transplant recipients are at risk for developing GVHD. Autologous and syngeneic transplant recipients are less likely to have chronic or late posttransplantation complications. Nonmyeloablative transplant recipients are less likely to develop opportunistic infections and other complications in the period immediately following transplantation, but are at risk for developing chronic GVHD and other chronic complications. Radiologic evaluation serves as the cornerstone for timely diagnosis of these complications, which is essential to reduce patient morbidity and mortality. Combining clinical factors-including the type of transplant and the point of time during the posttransplantation course-with characteristic imaging features yields the most specific and accurate differential diagnosis for radiologic findings in stem cell transplant recipients.
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PMID:Imaging evaluation of pulmonary and abdominal complications following hematopoietic stem cell transplantation. 1579 50

We evaluated autopsy-proven invasive fungal infections (IFI) in patients with hematologic malignancies over three periods (1989-1993, 1994-1998, and 1999-2003). The autopsy rate declined significantly (67%-34%-26%, respectively p<0.0001). IFI were identified in 314 (31%) of 1017 autopsies. Most IFI (75%) were not diagnosed antemortem. The prevalence of invasive mold infections increased significantly (19%-24%-25% p=0.05) in parallel with the emergence of Zygomycetes (0.9%-4%-3%; p=0.03). The prevalence of all other IFI remained relatively constant. Among patients with invasive pulmonary aspergillosis, those with graft-versus-host disease had a histopathological pattern distinct from those with neutropenia. The complex and evolving epidemiology of IFI in severely immunocompromised patients is not well captured by current diagnostic methods.
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PMID:Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989-2003). 1675 15

Zygomycoses are rare but often lethal mold infections predominantly affecting immunocompromised patients. Over the last years, several tertiary-care cancer centers reported an increase in the incidence of zygomycete infections in allogeneic blood stem cell transplant recipients. These observations are based on a small number of patients and should be considered in the context of a decades-long increase of mold infection rates. Diagnostic obstacles, including the difficult discrimination from the tenfold more frequent aspergilloses, may confound the reported incidences of zygomycete infections. These may be due to changes in frequency, severity and management of graft-versus-host disease promoting filamentous fungal infections, including zygomycoses. Hospitals applying long-term voriconazole prophylaxis in high-risk patients report a significant decrease in aspergillosis rates since the drug became available in 2001. The observation of increased frequencies of zygomycete infections during this period of time is not based on prospective evaluations. Therefore, the causes of these findings remain a matter of debate. Current multicenter trials on antifungal prophylaxis in high-risk patients promise to generate reliable data on the protective effect of antifungals active against molds, and the incidence of zygomycete infections in a controlled setting.
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PMID:[Zygomycosis after hematogeneic stem cell transplantation--a current problem?]. 1697 97

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

Posaconazole is a triazole antifungal agent with a spectrum of activity that includes Candida and Cryptococcus species, many molds, and some endemic fungi. Posaconazole has received US Food and Drug Administration approval for the treatment of oropharyngeal candidiasis, including infections refractory to itraconazole and/or fluconazole. It is also approved as prophylaxis for invasive Aspergillus and Candida infections in patients aged >or=13 years who are at high risk of developing these infections, in adult and adolescent hematopoietic stem cell transplant recipients with graft-versus-host disease, and in persons with hematologic malignancies and prolonged neutropenia due to chemotherapy, who are at high risk of developing these infections. Approval for additional indications is being sought. Limited clinical experience suggests efficacy for the treatment of infections due to Zygomycetes and as salvage therapy for patients with invasive aspergillosis and coccidioidomycosis. Currently available only as an oral suspension, posaconazole, which has been well tolerated, requires administration with food or a nutritional supplement to assure adequate bioavailability. Posaconazole is predominantly eliminated in the feces, where it appears as unchanged drug. Metabolism, mostly glucuronidation, plays only a minor role in its elimination, as does renal clearance; as a consequence, dose adjustment is not required in the presence of renal or hepatic insufficiency. Although not a substrate of hepatic CYP450 3A4, posaconazole inhibits this enzyme and thus has the potential for significant pharmacokinetic interactions with drugs metabolized by this isoform. Its use in combination with CYP450 substrates that prolong the QTc interval is contraindicated, as is its use with ergot alkaloids; administration of posaconazole with other substrates and/or inducers of this enzyme system requires caution. Posaconazole is both a substrate and inhibitor of P-glycoprotein. Currently, the major roles for posaconazole in clinical practice are as prophylaxis for neutropenic patients with significant risk of infection with filamentous fungi and as therapy for zygomycoses. It may also have a role in the treatment of other filamentous fungal and some yeast infections, but assessment of its overall place in antifungal therapy awaits the availability of further clinical experience.
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PMID:Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. 1841 3

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

Fungi cause severe infections in solid organ transplant (SOT) recipients. Recently, a shift towards non-Aspergillus filamentous fungal infections (nAFFI) was noticed. In a series of 2878 SOTs (kidney, pancreas, islets, liver, heart, lung, and bowel) performed between January 1995 and December 2006 at the Innsbruck medical university, eleven cases of nAFFI were diagnosed. The encountered species included Zygomyzetes (n = 8), and Alternaria alternate, Pseudallescheria boydii, Trichoderma spp. (one each); there were three liver and three heart, one intestinal, pancreas, lung, bilateral forearm and renal recipient each. Five patients died from nAFFI (zygomycosis: 4, Pseudallerichia boydii: 1); four were diagnosed postmortem. In five cases infection was surgically treated in combination with antifungals. Risk factors for nAFFI were renal failure (73%) and intensified immunosuppression (73%); two cases were associated with post-transplant lymphoproliferative disorder, one with graft versus host disease. An increase in the incidence of nAFFI was observed parallel to introduction of caspofungin and voriconazole (three cases until 12/2003, seven cases thereafter). NAFFI are increasingly found in SOT recipients. If diagnosed in time, the outcome seems acceptable. Intensified immunosuppression and exposure to antifungals not active against zygomycetes may be risk factors. Surgical therapy may play an important role in these infections.
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PMID:Zygomycosis and other rare filamentous fungal infections in solid organ transplant recipients. 1836 72


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