Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two different treatments with repeated oral high doses of itraconazole were tested for 10 days in 20 neutropenic patients, 10 receiving 400 mg per day and 10 receiving 600 mg per day. In each group 5 patients were treated for acute leukaemia and 5 patients were recipients of autologous bone-marrow transplantation (ABMT). Itraconazole plasma concentrations were assayed by high-performance liquid chromatography. Statistical analysis disclosed a significant interaction between the dispensed dose and the patient types. The difference between the two doses of itraconazole was greater in the ABMT than in the leukaemia patients. After 10 days at 600 mg per day all the ABMT patients had an itraconazole plasma concentration higher than 250 micrograms/l. Therefore, 600 mg per day seems more efficient to obtain a therapeutic level of itraconazole in ABMT patients but this needs to be confirmed for all the neutropenic patients.
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PMID:Plasma itraconazole concentrations in neutropenic patients after repeated high-dose treatment. 132 9

We report on the treatment of invasive aspergillosis with the new triazole antimycotic agent itraconazole. All 11 patients suffered from pulmonary invasive aspergillosis. Two patients also had cerebral aspergillosis; in one of these patients the paranasal sinuses were also invaded. Underlying diseases were acute lymphoblastic leukaemia (n = 3), acute myeloid leukaemia (n = 4); one patient underwent allogeneic bone marrow transplantation before he developed aspergillosis; another was transplanted after successful aspergillosis treatment, liver cirrhosis (n = 1), lung infarction after pulmonary embolism (n = 1), chronic bronchitis after pulmonary tuberculosis (n = 1) and AIDS (n = 1). In five cases initial diagnosis was established by means of mycological methods and clinical signs. In six patients invasive pulmonary aspergillosis was initially diagnosed due to the clinical criteria presented in this paper. Secondary mycological confirmation after onset of therapy was achieved in five out of these six patients. All of the patients initially responded to therapy. One female patient experienced a relapse of aspergillosis and died of cerebral involvement and relapsing leukaemia. Two further patients died due to underlying diseases (pulmonary embolism, relapsing leukaemia). Nine patients (82%) were cured of the mycosis, including the patient with cerebral involvement; two underwent surgical resection of residual pulmonary lesions. Itraconazole is a very effective drug for treatment of invasive aspergillosis. Therapeutic efficacy can be optimized by early diagnosis using clinical criteria and prompt start of treatment.
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PMID:Therapy of invasive aspergillosis with itraconazole: improvement of therapeutic efficacy by early diagnosis. 166 78

During indoor building renovation a nosocomial epidemic of pulmonary aspergillosis occurred in a haematological ward, involving 10 patients with acute leukaemia undergoing intensive chemotherapy. Antifungal treatment included the combination of amphotericin B and 5-fluorocytosine during periods of granulocytopenia, followed by itraconazole after bone-marrow recovery. In five patients, lung aspergillomas disappeared completely, while significant improvement was observed in a further two patients. Itraconazole appeared to contribute significantly to the result, but the drug did not work during granulocytopenic episodes. Air analyses showed increased counts of fungal spores in ward locations with heavy traffic of patients and staff, suggesting the need to identify and avoid risk areas when placing patients undergoing intensive chemotherapy.
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PMID:Itraconazole treatment of pulmonary aspergillosis in leukaemia patients during a nosocomial epidemic associated with indoor building renovation. 166 79

Itraconazole is a recently developed triazole antifungal agent that inhibits cell membrane sterol biosynthesis. Itraconazole, in a dose-dependent manner, enhanced intracellular accumulation of daunorubicin and reversed the drug resistance in murine leukemia P388/ADR cells. In addition, itraconazole corrected the altered plasma membrane potentials of P388/ADR cells. The concentrations of itraconazole that reversed drug resistance are comparable to the plasma levels achieved by therapeutic dosage used in the treatment of fungal infections. Therefore, itraconazole is a potential candidate for in vivo use to reverse multidrug resistance in cancer with added benefit of its antifungal property.
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PMID:Reversal of daunorubicin resistance in P388/ADR cells by itraconazole. 184 51

During a period of 32 months (August 1986 until April 1989) 108 patients (74 women, 34 men; mean age 53 years) with neoplastic diseases (59 patients with solid tumors, 45 patients with lymphomas, two patients with acute leukaemias, one patient with chronic myelogenous leukaemia, one patient with aplastic anaemia) were studied in the Department of Internal Medicine of the University Erlangen-Nuremberg. Most were treated with a cytostatic chemotherapy. In order to prevent a mycotic infection in these immunocompromised patients, itraconazole, a new broad-spectrum antimycotic drug of the azole group, was given in an oral dosage of 100 mg day-1 (mean duration of prophylactic treatment 24 months). Localized Candida infections involving the oropharynx and the female genital organs were diagnosed in 16 patients (14.8%). Candida endophthalmitis occurred in one patient (0.9%). The serum concentration of Candida antibodies was significantly elevated in one patient (0.9%) without evidence of fungemia. Itraconazole had to be discontinued in four cases (3.7%) due to minor side effects of the drug (nausea, stomach complaints). Itraconazole appears to be a safe and effective antimycotic drug in long-term use in neutropenic patients.
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PMID:Prophylaxis of fungal infections with itraconazole in immunocompromised cancer patients. 217 92

Cryptococcosis and aspergillosis in immunocompromised patients are extremely difficult clinical conditions to manage and treatment with available antifungal drugs often fails. Itraconazole, R-51211, Janssen Pharmaceutica, a new orally absorbed triazole, is a possible alternative drug which is potentially effective and nontoxic. Preliminary experience with 28 patients, eight with cryptococcosis and 20 with aspergillosis, is reported. Of these patients, 16 were immunocompromised (seven with the acquired immune-deficiency syndrome (AIDS), five heart transplant recipients and four with leukaemia or lymphoma). Overall, results of treatment were good (18 in remission, four markedly improved, four moderately improved and two failed). Prevention of relapses of cryptococcosis was obtained in all patients with AIDS on long-term itraconazole monotherapy (3 mg/kg). Treatment of invasive aspergillosis required a higher dosage (about 5 mg/kg) and prolonged administration. Besides its efficacy this antifungal agent allowed outpatient management.
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PMID:Experience with itraconazole in cryptococcosis and aspergillosis. 254 Feb 43

A 13 year-old girl was diagnosed as having acute megakaryoblastic leukemia. A serious infectious syndrome appeared during the chemotherapy, not improved by broad spectrum antibiotic therapy. A pulmonary aspergillosis was diagnosed one month later by a second bronchoalveolar lavage. A treatment with Itraconazole, a new antifungal triazole, was started. Despite this treatment, the child died after 3 days. Death was due to multiple aspergillus abscesses disseminated in the brain leading to coma and transtentorial herniation. Autopsy confirmed the cerebral aspergillus abscesses and showed also the dramatic dissemination of aspergillosis in the body. Diagnosis and treatment to aspergillosis in immunosuppressed patients should be made early to improve prognosis.
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PMID:[Fatal cerebral aspergillosis in acute megakaryoblastic leukemia]. 265 61

Some generalizations regarding fungal infections of the larynx can be made. The reader is cautioned to refer to discussions of the individual infections for exceptions to these generalizations. For the most part, the mycoses are organisms of low pathogenicity emerging as opportunistic organisms thriving in a compromised host. The isolated fungal infections of the larynx reported are exceptions to the rule. Involvement of the larynx and other body sites outside the lung generally indicates a widely disseminated form of the disease. Fungal infections most commonly occur in the immunocompromised patient, including those afflicted with AIDS, cancer, leukemia, and other lymphoreticular neoplasms, patients on long-term corticosteroid therapy, patients with chronic systemic diseases, including diabetes mellitus and severe pulmonary disease, and patients who have undergone successful organ transplantation, which depends on immunologic suppression. Although specific fungi are characteristically found in designated endemic areas, the diseases may surface in remote areas in persons who have recently traveled through the endemic sites. The pathologic picture can be confusing, and pseudoepitheliomatous changes at times resemble malignancy. When atypical features occur in a patient with a suspicious history, special stains and cultures as well as skin tests and serologic studies may be helpful in establishing the diagnosis. For the most part, amphotericin B has been the mainstay of therapy, although the introduction of the newer azole drugs (ketoconazole, itraconazole and fluconazole) may present a breakthrough in the future therapy of these lesions. Ketoconazole has been proven efficacious in certain fungal infections. Itraconazole has recently been released for clinical use. Because of its lower incidence of toxic side effects, it may replace ketoconazole in the therapy of these diseases. Finally, fluconazole, taken orally, effectively crosses the blood-brain barrier; appropriate clinical trials may prove it to be an acceptable agent for those fungi commonly affecting the central nervous system.
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PMID:Fungal infections of the larynx. 829 Feb 83

The relationship between treatment outcome and location of cryptococcal infection, gender, magnitude of pretreatment cryptococcal antigen titers, results of feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) serology, and serial changes in antigen titers during and after treatment were evaluated in a prospective and nonrandomized study of 35 cats with cryptococcosis. A commercial cryptococcal latex agglutination kit (CALAS; Meridian Diagnostic Inc, Cincinnati, OH) was used to detect cryptococcal antigen in sera. All cats were treated with itraconazole (Sporanox; Janssen Pharmaceutica Inc, Titusville, NJ). Pretreatment mean log titers for serum cryptococcal antigen were not influenced by location of the infection. Treatment outcome was not influenced by gender, location of the infection, or magnitude of pretreatment serum antigen titer. Treatment outcome was influenced by FeLV and FIV status; cats seropositive for FeLV or FIV had a higher likelihood of treatment failure (P = .008). The cryptococcal antigen titers of cats successfully treated decreased with significant linearity over time during treatment (r = -.64, P < .000001), whereas the corresponding titers for cats not treated successfully did not decrease with significant linearity (r = -.03, P > .9). For cats in which treatment was successful, antigen titers decreased significantly from pretreatment values by 1.3 orders of magnitude at 2 months after initiation of treatment. By 10 months after initiating treatment, log titers decreased by at least 2 orders of magnitude in all cats successfully treated, and 9 of 16 cats had undetectable titers. In contrast, in 5 of 6 cats in which treatment failed, antigen titers were unchanged or increased in magnitude even after at least 6 months of treatment.
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PMID:Cryptococcal infection in cats: factors influencing treatment outcome, and results of sequential serum antigen titers in 35 cats. 913 77

Fungal colonization has been associated with an increased rate of invasive fungal infections in neutropenic patients. This study evaluates weekly fungal surveillance cultures from the oropharyngeal and perianal space as well as other suspected sites in 219 courses of myelosuppressive chemotherapy with itraconazole antifungal prophylaxis in 116 neutropenic patients with acute leukaemia. Itraconazole was given from the start of chemotherapy in one of six different dosing regimens. Fungal colonization occurred in 68 (31%) of courses, which was lower than in a historical control group without prophylaxis (53%, P = 0.004). Twenty-six per cent of these 116 isolates had a growth rate of more than 50 colony forming units (CFU) per culture. Candida glabrata (51%), Candida albicans (18%) and Candida krusei (4%) were the most frequently isolated species. Higher median itraconazole trough concentrations were associated with a lower growth rate in the cultures (< or = 50 CFU/culture versus > 50 CFU/culture): 710 (430-1180) ng ml-1 versus 900 (560-1650) ng ml-1 (P = 0.015). The use of itraconazole solution--compared with capsules--led to a reduced growth rate (P = 0.035). In conclusion, compared with historical controls itraconazole antifungal prophylaxis reduces the incidence and the extent of fungal colonization during neutropenia in patients with acute leukaemia.
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PMID:Fungal surveillance cultures during antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia. 1053 31


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