Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fungal infections due to Aspergillus are a frequent cause of transplant-related mortality. For this reason, leukemic patients with severe fungal infection are usually excluded from conventional allotransplantation. Recently, some authors suggested a role for non-myeloablative hematopoietic stem cell transplantation (HSCT) in this subset of patients. We used this therapeutic approach in a patient with high-risk acute myeloid leukemia in second complete remission (CR) with pre-existing hepatic aspergillosis refractory to conventional anti-fungal therapy. A complete regression of hepatic lesions was observed after 3 months from allogeneic stem cell transplantation. Our work confirms previous reports suggesting that non-myeloablative HSCT is effective in patients not eligible for conventional transplantation because of invasive aspergillosis.
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PMID:Complete resolution of hepatic aspergillosis after non-myeloablative hematopoietic stem cell transplantation in a patient with acute myeloid leukemia. 1627 26

To study the changes of visceral mycoses in autopsy cases, data on visceral mycosis cases with leukemia and myelodysplastic syndrome (MDS) reported in the Annual of the Pathological Autopsy Cases in Japan in 1989, 1993, 1997 and 2001 were analyzed. The frequency rate of visceral mycoses with leukemia and MDS was 27.9% (435/1,557) in 1989, 23.0% (319/1,388) in 1993, 22.3% (246/1,105) in 1997 and 25.1% (260/ 1,037) in 2001, which was clearly higher than the rate of cases without leukemia and MDS: 3.4%, 2.7%, 3.5% and 3.7%, respectively. Furthermore, in comparing the rate of mycoses in recipients of stem cell transplantation with that of non-recipients, that of recipients was about 10% higher. The predominant causative agents were Candida and Aspergillus, at approximately the same rate (Candida 33.6%, Aspergillus 33.3%) as in 1989. However, Aspergillus increased conspicuously in 1993 (Candida 22.3% Aspergillus 44.5%), and continued to increase (Candida 22.8%, Aspergillus 50.8% in 1997; Candida 16.9%, Aspergillus 54.2% in 2001). In aspergillosis and zygomycosis, the lung and bronchi comprised the most commonly infected organs: 74.7% and 75.6% of the total cases, respectively. Among a total of 1,260 cases with mycotic infections in the four years studied, acute lymphatic leukemia and acute myeloid leukemia were the major diseases (35.5% and 33.5%, respectively) followed by MDS (29.0%). Given these facts, we emphasize that a greater interest in mycoses should be taken by clinicians, and immunocompromised patients should be protected from opportunistic invasive fungal infections, especially aspergillosis.
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PMID:[Epidemiology of visceral mycoses in patients with leukemia and MDS - Analysis of the data in annual of pathological autopsy cases in Japan in 1989, 1993, 1997 and 2001]. 1646 36

The cytotoxic effect of cytarabine (Ara-C) on myeloid leukemic cells is enhanced by concomitant use of granulocyte colony-stimulating factor (G-CSF) in vitro. The feasibility of a conditioning regimen consisting of G-CSF-combined 24 g/m2 Ara-C, 90 mg/m2 fludarabine, and 12 Gy total body irradiation was studied for five patients with acute myelogenous leukemia in cord blood transplantation (CBT). Graft vs. host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. After the conditioning regimen, 2.48 x 10(7)/kg (2.28-3.53) of cord blood nucleated cells was infused. Neutrophil counts consistently >0.5 x 10(9)/L was achieved 24 d (22-32) after CBT. Grade I stomatitis and gastrointestinal toxicities occurred in all patients. Grades I and II acute GVHD occurred in one and four patients, respectively, which resolved without steroid therapy. Sepsis and aspergillosis occurred in two and one patients, respectively. All patients were alive without leukemia relapse at a follow up of 15 months (12-43) after CBT. This conditioning regimen could avoid the toxicities of high-dose cyclophosphamide but might enhance the cytotoxic effect of Ara-C. Large-scale studies will be needed to determine the efficacy and safety of the conditioning regimen in CBT.
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PMID:Cord blood transplantation for acute myelogenous leukemia using a conditioning regimen consisting of granulocyte colony-stimulating factor-combined high-dose cytarabine, fludarabine, and total body irradiation. 1657 43

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase I dose-finding trial. A starting dose of 0.5 mg m(-2) day(-1) was explored with subsequent dose escalations of 1, 3, 5 and 6 mg m(-2) day(-1). Myelosuppression was constant. The MTD was estimated as the dose level of 5 mg m(-2) day(-1) for 9 consecutive days by s.c. route. Dose-limiting toxicities were hyperglycaemia with hyperosmolar coma at 3 mg m(-2), and (i) one anasarque and haematemesis, (ii) one life-threatening pulmonary aspergillosis, (iii) one skin rash and (iv) one scalp pain at dose level of 5 mg m(-2) day(-1). The mean half-life of ssHHT was 11.01+/-3.4 h, the volume of distribution at steady state was 2+/-1.4 l kg(-1) and the plasma clearance was 11.6+/-10.4 l h(-1). Eleven of the 12 patients with circulating leukaemic cells had blood blast clearance, two achieved complete remission and one with blast crisis of CMML returned in chronic phase. The recommended daily dose of ssHHT on the 9-day schedule is 5 mg m(-2) day(-1).
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PMID:A phase I dose-finding and pharmacokinetic study of subcutaneous semisynthetic homoharringtonine (ssHHT) in patients with advanced acute myeloid leukaemia. 1684 70

An infant with congenital acute myelocytic leukemia, who was being treated with chemotherapeutic agents, developed obstruction and infarction of the ileum due to occlusion of mesenteric arteries by Aspergillus hyphae. This case demonstrates how blood vessel occlusion by occult aspergillosis can present clinically as a surgical emergency.
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PMID:Aspergillus-induced small bowel obstruction in a leukemic newborn. 1697 56

Posaconazole is a lipophilic triazole antifungal agent that is structurally similar to itraconazole but has an expended spectrum of activity including yeast, molds, and dimorphic fungi. Posaconazole was licensed by the European Commission for the treatment of invasive aspergillosis, fusariosis, mycetoma, chromoblastomycosis, and coccidioidomycosis in adults who are refractory, or intolerant to other antifungal agents. Posaconazole was recently indicated for prophylaxis of invasive fungal infections in the following patients: patients receiving remission-induction chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) expected to result in prolonged neutropenia and hematopoietic stem cell transplant (HSCT) recipients who are undergoing high-dose immunosuppressive therapy for versus host disease. The spectacular activity of posaconazole against refractory infections due to zygomycetes is encouraging and suggests using posaconazole in this case. Posaconazole is only available in oral suspension formulation. Posaconazole was well tolerated in clinical trials and has lower drug interaction profile compared to other available azoles.
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PMID:[The latest data on posaconazole]. 1726 54

We describe 2 patients who developed prolonged QTc interval on electrocardiogram while being treated with voriconazole. The first patient had undergone induction chemotherapy for acute myelogenous leukemia, and her course had been complicated by invasive aspergillosis and an acute cardiomyopathy. She developed torsades de pointes 3 weeks after starting voriconazole therapy. She was re-challenged with voriconazole without recurrent QTc prolongation or cardiac dysfunction. The second patient had a significantly prolonged QTc interval while on voriconazole therapy. We recommend careful monitoring for QTc prolongation and arrhythmia in patients who are receiving voriconazole, particularly those who have significant electrolyte disturbances, are on concomitant QT prolonging medications, have heart failure such as from a dilated cardiomyopathy, or have recently received anthracycline-based chemotherapy. The potential for synergistic cardiotoxicity must be carefully considered.
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PMID:Torsades de pointes associated with voriconazole use. 1731 69

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

We report the development of invasive pulmonary aspergillosis in a patient treated for acute myeloid leukaemia during empirical voriconazole therapy for febrile neutropenia. The patient failed to respond to the institution of salvage combination therapy with amphotericin B and voriconazole, but survived after adjunctive surgical resection.
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PMID:Breakthrough invasive pulmonary aspergillosis despite empirical voriconazole therapy for febrile neutropenia: case report and review of the literature. 1765 53

Morbidity and mortality caused by invasive Aspergillus infections are increasing. This is because of the higher number of patients with malignancies treated with intensive immunosuppressive therapy regimens as well as their improved survival from formerly fatal bacterial infections, and the rising number of patients undergoing allogeneic haematopoietic stem cell or organ transplantation. Early initiation of effective systemic antifungal treatment is essential for a successful clinical outcome in these patients; however, clinical clues for diagnosis are sparse and early microbiological proof of invasive aspergillosis (IA) is rare. Clinical diagnosis is based on pulmonary CT scan findings and non-culture based diagnostic techniques such as galactomannan or DNA detection in blood or bronchoalveolar lavage samples. Most promising outcomes can be expected in patients at high risk for aspergillosis in whom antifungal treatment has been started pre-emptively, backed up by laboratory and imaging findings. The gold standard of systemic antifungal treatment is voriconazole, which has been proven to be significantly superior to conventional amphotericin B and has led to a profound improvement of survival rates in patients with cerebral aspergillosis. Liposomal amphotericin B at standard dosages appears to be a suitable alternative for primary treatment, while caspofungin, amphotericin B lipid complex or posaconazole have shown partial or complete response in patients who had been refractory to or intolerant of primary antifungal therapy. Combination therapy with two antifungal compounds may be a promising future strategy for first-line treatment. Lung resection helps to prevent fatal haemorrhage in single patients with pulmonary lesions located in close proximity to larger blood vessels, but is primarily considered for reducing the risk of relapse during subsequent periods of severe immunosuppression. Strict reverse isolation appears to reduce the incidence of aspergillosis in allogeneic stem cell transplant recipients and patients with acute myeloid leukaemia undergoing aggressive anticancer therapy. Well designed, prospective randomised studies on infection control measures effective to prevent aspergillosis are lacking. Prophylactic systemic antifungal treatment with posaconazole significantly improves survival and reduces IA in acute myeloid leukaemia patients and reduces aspergillosis incidence rates in patients with intermediate-to-severe graft-versus-host reaction emerging after allogeneic haematopoietic stem cell transplantation. Voriconazole prophylaxis may be suitable for prevention of IA as well; however, the results of large clinical trials are still awaited.
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PMID:Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients. 1766 28


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