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)

The efficiency of stored platelet transfusion was evaluated in terms of clinical status in 136 thrombocytopenic patients. In a paired prospective study in which fresh platelets were used as controls, clinical efficiency was assessed on the basis of the ability to increase platelet count (recovery) and the interval to the next transfusion (D). In 48 clinically stable patients, recovery of fresh and stored platelets was similar (47% and 41% respectively) and the interval to the next transfusion was D4 and D3. In contrast, 27 patients who had bacterial infections showed significantly different recoveries (24%/5%) and the interval to the next transfusion was D3/D1 for fresh and stored platelets respectively. Similarly, in 16 patients who were treated concurrently with Amphotericin B, 18 other patients with graft-versus-host disease, 5 with splenomegaly and 3 with veno-occlusive disease (VOD), fresh platelets performed better than stored platelets, showing recoveries of 27%/18%, 29%/15%, 15%/1%, 22%/3%. Furthermore, the need for retransfusion within 24 hours was significantly increased with stored platelets. In 19 patients with anti-HLA allo-immunization who were transfused with HLA-matched fresh and stored APC, efficiency was similar (38%/36% and D4/D3). This study indicates that the storage has a major detrimental effect on platelet recovery and survival in patients with certain clinical conditions.
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PMID:[Influence of clinical status on the efficacy of stored platelet transfusion]. 825 53

Invasive aspergillosis in bone marrow transplant recipient is associated with a high mortality. Diagnosis is often delayed because the inflammatory response is blunted by immunosuppression. The gold standard of tissue biopsy is often considered too in invasive as the procedure is often complicated by bleeding and secondary infection. Recent finding on non-invasive tests such as serial measurement of peripheral blood galactomannan antigen or DNA appears to be promising. However, the limited availability of such tests and requirement for expertise are still hampering their use in routine clinical management. More often than not, initiation of antifungal therapy is empirical and based on suggestive radiological changes. Amphotericin B remains the gold standard of therapy but liposconal preparation may prove to be less nephrotoxic and equally effective. Treatment outcome depends more on the acceleration of the recovery of the immune system and the reduction of anti-GVHD therapy than the antifungal agent followed by surgical resection. The efficacy of many reported anti-aspergillosis prophylactic regimen has not been proved in randomized control trials. Despite the absence of data, such policy should still be considered in transplant units with high incidence of aspergillus or undergoing renovation.
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PMID:Aspergillosis in bone marrow transplant recipients. 1078 48

The use of high-dose corticosteroids for graft-versus-host disease (GVHD) treatment represents a major risk factor for long-term invasive fungal infections. The aim of this study was to investigate the safety and tolerance of weekly prophylactic administration of once-weekly high-dose (7.5 mg/kg) of liposomal amphotericin B (L-AmB) therapy in 21 adult patients receiving high-dose prednisone (2 mg/kg/day) for acute GVHD therapy after reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). Patients received a median of 4 (range, 1-8) infusions of L-AmB. Seven patients (33%; 95% confidence intervals (CI), 13-53%) discontinued taking the study drug owing to study drug-related adverse events, including elevated serum creatinine (>1.5 times from baseline values; n=5), hypotension and pain (n=1), and violent chest pain and arrhythmia (n=1). The overall frequency of infusion-related reactions was 29% (n=6; 95% CI, 10-48%), but these reactions were always transient and relieved by stopping the infusion. This safety data provide support for an efficacy study of this prophylaxis strategy, because this may help further improving the outcome of RIC or nonmyeloablative allo-SCT.
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PMID:High-dose weekly liposomal amphotericin B antifungal prophylaxis following reduced-intensity conditioning allogeneic stem cell transplantation. 1726 59

The last twenty years, the incidence of invasive fungal infections (IFI) has risen dramatically due to the prolongation of survival of patients with multiple risk factors for fungal infections. Amphotericin B was for more than 40 years the gold standard for almost all IFI, but toxicity and resistance, especially of new and emerging pathogens remained important issues. Fluconazole and itraconazole have also the same disadvantage of resistance. Voriconazole, a new triazole antifungal has offered an additional option, but the problem of resistant aspergillosis, and zygomycosis remains. Echinocandins (caspofungin, micafungin and anidulafungin) are active only against Candida and Aspergillus spp., but not against Fusarium, Scedosporium and Zygomycetes. Posaconazole is the most recently approved triazole with broad spectrum activity against Candida spp., Aspergillus spp., Cryptococcus neoformans, Zygomycetes, dermatiaceous, dimorphic, and other fungal pathogens. Interestingly, posaconazole is active against Candida spp., resistant to fluconazole and itraconazole, and Aspergillus fumigatus resistant to fluconazole itraconazole, amphotericin B, and voriconazole. The results from clinical trials of posaconazole as salvage treatment are encouraging. Multicenter clinical trials have also established its role in the prophylaxis of (IFI) in the severely immunocompromised patients such as those after hematopoietic stem cell transplantation (HSCT) who developed graft versus host disease (GVHD), as well as the neutropenic patients with an acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after myeloablative chemotherapy. Posaconazole has pharmacokinetic advantages and low side effect profile, which are very important, especially in the seriously ill population.
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PMID:Posaconazole: a new antifungal weapon. 2168 87

In patients with invasive aspergillosis (IA), there are numerous clinical settings where stable disease or progression of findings or deterioration of the patient's condition does not indicate failure, and subsequent response to a 'salvage' antifungal is not necessarily attributable to this drug. Many patients, in whom pulmonary aspergillosis emerges during profound neutropenia, show enlargement of their lesions on computer tomography (CT) scans, eventually accompanied by clinical deterioration, during hematopoietic recovery. This may in fact represent the recruitment of neutrophils and monocytes to the pulmonary 'battlefield', resulting in a favorable clinical outcome also without changing antifungal treatment. Infarcted tissue may contain vital filamentous fungi, because it is poorly penetrated by the antifungal, not indicating a lack of efficacy of this drug against the respective fungal pathogen. In patients treated with an echinocandin, serum galactomannan levels may increase despite successful treatment. Piperacillin-tazobactam or other semi-synthetic beta-lactam antibiotics may cause false positive serum Aspergillus galactomannan levels. Patients primarily treated with a lipid formulation of AmB (LF-AmB), who are switched to a 'salvage' antifungal, will unequivocally receive a combination therapy due to the persistence of high LF-AmB concentrations in tissue. Criteria to define 'clinical refractoriness', 'resistance', 'non-response' or 'failure' respectively should be re-defined. One option to establish a more valid definition would be to use a composite score including clinical as well as radiological and microbiological or mycological criteria. The latter may include non-culture based methods such as serum galactomannan. Assessment should not be made earlier than after seven days of full-dose systemic antifungal treatment. However, in individual cases, e.g. a patient with hematopoietic recovery, who shows an increasing volume of pulmonary aspergillosis and clinical deterioration, it may be recommended to refrain from switching the patient to another regimen and continue the current antifungal treatment for another seven days before failure is stated. Clinical studies on second-line antifungal treatment for IA should be randomized and blinded, patients should be evaluated separately with respect to their reason for 'failure' of primary antifungal treatment, and stratified according to their previous antifungal treatment. Ideally, the first-line regimen would be standardized. Host criteria such as neutropenia or graft-versus-host disease (GVHD) should be clearly defined and documented with respect to their course over time, and patients should be stratified according to these criteria. A three-arm study (continuation of primary antifungal vs. combination of primary antifungal with a 'salvage' drug vs. the 'salvage' drug alone) would be ideal.
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PMID:Defining clinical failure for salvage studies. 3040 23