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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic Candida infections are a major cause of infectious morbidity and mortality during chemotherapy-induced neutropenia. Because of the unreliability of conventional diagnostic tests to detect systemic infection early in its course, treatment of established disseminated Candida infection has been generally disappointing with mortality rates of 60-80% in leukemia and bone marrow transplant patients and 30-40% in solid tumor patients. The use of empiric amphotericin B in patients with fever not responding to empiric antibacterial agents has been shown to be successful in reducing morbidity and mortality from fungal infections. However, its toxicity has mitigated the success of this approach. Fluconazole given prophylactically at the institution of chemotherapy has been shown to be a safe and effective alternative. It, however, is not active against all fungal species, especially Aspergillus and some of the less virulent Candida species. Some centers have reported break-through infections by these less susceptible organisms. Whether or not these limitations in its spectrum of activity will limit its usefulness in the future remains unanswered at this time and could pose a cloud to an otherwise bright promise.
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PMID:The use of fluconazole prophylaxis in patients with chemotherapy-induced neutropenia. 129 Sep 59

In a prospective randomized study the efficacy of fluconazole (50 mg in one single daily dose) was compared with oral amphotericin B in suspension and tablets (each 200 mg four times daily) for prevention of colonization and subsequent infection by yeasts in 50 patients undergoing remission induction treatment for acute leukaemia. All patients received ciprofloxacin for prevention of bacterial infections. Fluconazole was as effective as amphotericin B in preventing severe local and disseminated fungal disease (one documented and one highly suspected infection in each group of patients). Fluconazole effectively prevented yeast colonization of the oropharynx but was less effective than amphotericin B in preventing colonization of the lower alimentary tract. Fifty-two percent of patients receiving fluconazole had persistent positive stool cultures as compared to 4% in the amphotericin B group (P less than 0.01). Fluconazole was better tolerated than amphotericin B. One patient developed an extended rash leading to the termination of fluconazole.
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PMID:A randomized study to compare oral fluconazole to amphotericin B in the prevention of fungal infections in patients with acute leukaemia. 203 41

Fluconazole is a new orally absorbed antifungal azole which is effective in the treatment of mucosal and systemic infections caused by Candida, cryptococci and other fungi. In view of its favourable efficacy, safety and pharmacokinetic profile it was considered appropriate to evaluate its use prophylactically in patients undergoing a period of neutropenia. Two hundred and forty-eight patients receiving chemotherapy and/or bone marrow transplantation for the treatment of acute leukaemia, lymphoma or aplastic anaemia, and expected to be rendered temporarily neutropenic, have been entered into an ongoing multicentre comparative clinical study to compare the prophylactic efficacy of 50 mg daily oral fluconazole with that of widely used regimens of oral polyenes. The incidence of suspected fungal infection was less in the fluconazole group (27%) than in the polyene group (45%), the difference being statistically significant (P less than 0.05). Only one of the suspected infections in the fluconazole group was confirmed mycologically compared with 17 in the polyene group. Fluconazole prophylaxis was well tolerated and it therefore offers a promising new approach to the management of fungal infection in the neutropenic patient. Further studies are warranted to define the optimum dosage for use in this situation.
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PMID:Management of fungal infection in neutropenic patients with fluconazole. 218 47

A multicenter clinical study of fluconazole was conducted at 41 hospital sites in Japan. Fluconazole was administered orally or intravenously at daily doses of 50 to 400 mg to 199 patients with deep-seated mycoses. Clinical efficacy was evaluable in 125 of these patients. Most cases were complicated with serious underlying diseases such as cancer, leukemia, or AIDS. Clinical cures were achieved in 56 (87.5%) of 64 cases of candidiasis, in 11 (68.8%) of 16 cases of cryptococcosis, in 19 (44.2%) of 43 cases of aspergillosis, and in one case each (100%) of mucormycosis and fungemia due to an unspecified yeast. Eradication rates of causative fungi were 87.9% in Candida spp., 62.5% in Cryptococcus neoformans, and 52.2% in Aspergillus spp. Side effects were observed in 13 cases, with an incidence rate of 6.5%. In most cases fluconazole was well tolerated. Changes in laboratory test values due to the drug were reported in 35 patients with an incidence rate of 17.6%. The changes were minor and transient; primarily increases in liver enzyme. Fluconazole is a useful antifungal agent for the treatment of systemic deep-seated mycoses.
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PMID:A clinical study of fluconazole for the treatment of deep mycoses. 255 41

All-trans-retinoic acid induces acute promyelocytic leukemia cell differentiation in vitro, and it produces greater than 90% complete remissions in patients with acute promyelocytic leukemia. Despite the high response rate, the majority of patients relapse with continued trans-retinoic acid therapy, and disease progression has been observed to be accompanied by an increase in the metabolism of trans-retinoic acid in the patients. In this study, the pharmacokinetic disposition of trans-retinoic acid was determined by HPLC in patients with acute promyelocytic leukemia before and after concurrent therapy with the triazole antimycotic agent fluconazole. Treatment with trans-retinoic acid for 1 week reduced the area under the plasma trans-retinoic acid concentration vs time curve in one patient by 67%, from 277 to 91 ng/mL/hr. Trans-retinoic acid pharmacokinetics were repeated after the second dose of fluconazole, administered 1 hour prior to the retinoid, and the AUC was found to be 401 ng/mL/hr, a greater than 4-fold increase from the pre-fluconazole level. A similar, though more modest, effect of fluconazole was seen in a second acute promyelocytic leukemia patient. The effect of fluconazole on trans-retinoic acid metabolism was examined in vitro using isolated human hepatic microsomes. Fluconazole inhibited the NADPH-dependent cytochrome P450-mediated catabolism of trans-retinoic acid in a concentration-dependent manner. Although fluconazole was approximately one-half as potent an inhibitor when compared with ketoconazole, a related antifungal drug, 60-90% inhibition was observed at the concentrations of fluconazole measured in the acute promyelocytic leukemia patients. Neither fluconazole nor ketoconazole inhibited lipid hydroperoxide-mediated metabolism of trans-retinoic acid. Since fluconazole is a well-tolerated agent frequently administered to leukemia patients, its use in combination with trans-retinoic acid merits further consideration.
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PMID:Inhibition of all-trans-retinoic acid metabolism by fluconazole in vitro and in patients with acute promyelocytic leukemia. 757 74

We studied the impact of fluconazole prophylaxis (400 mg/day) on clinical features including fever and use of amphotericin in a randomized, double-blind, placebo-controlled (1:1 randomization) study among patients undergoing chemotherapy for leukemia and those undergoing bone marrow transplantation. Fluconazole or placebo was given throughout the period of neutropenia. Amphotericin was administered to 5 of 23 (22%) fluconazole recipients and 14 of 23 (58%) placebo recipients (p < 0.01). Median duration of amphotericin used in fluconazole and placebo groups was 9 days (mean 10.8) and 13 days (mean 14) respectively. Patients who received fluconazole had significantly shorter duration of fever prior to treatment with amphotericin (days, median 5 vs. 9, p < 0.05). Superficial fungal infections were noted in 8 (34%) fluconazole recipients and 19 (79%) placebo recipients (p = 0.002). Fluconazole was well tolerated. Prophylaxis with fluconazole resulted in a significant reduction in the empiric use of amphotericin, duration of fever and incidence of superficial fungal infections.
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PMID:Effect of fluconazole prophylaxis on fever and use of amphotericin in neutropenic cancer patients. Bone Marrow Transplantation Team. 813 35

The impact of prophylaxis with 400 mg/day fluconazole on fungal colonization at different body sites was assessed in a randomized, double-blind, placebo controlled study among patients with leukaemia and those undergoing bone marrow transplantation. The study drug was given throughout the period of neutropenia and samples were obtained at weekly intervals. Of the 23 patients in each group, 11 of those given fluconazole and 12 placebo recipients were colonized at entry. The commonest sites were the oropharynx and rectum and Candida albicans was the most frequent isolate. Fluconazole led to a marked reduction in colonization by the second week of treatment to 29% compared with 68% for those given the placebo. Two-weeks after stopping the study regimen there was little change with yeast being isolated from 33% and 81% respectively. Fluconazole was particularly effective in reducing the carriage of C. albicans in the oropharynx from 46% to 0-10% and in maintaining this throughout prophylaxis. Recovery of Candida (Torulopsis) glabrata from the perianal region steadily increased to around 30% in both patient groups and while Candida krusei species were found exclusively in patients given fluconazole, other candida were more common in the placebo group. These results demonstrate that by rapidly reducing the colonization of the alimentary tract, fluconazole eliminates the major reservoir for infection with yeasts other than C. glabrata and C. krusei during the critical period of neutropenia.
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PMID:The effect of fluconazole prophylaxis on fungal colonization in neutropenic cancer patients. Bone Marrow Transplantation Team. 818 12

The medical records of patients with hematogenous candidiasis at M. D. Anderson Cancer Center (Houston) between 1988 and 1992 were retrospectively reviewed. There were 491 episodes of infection (6 per 1,000 admissions), 79% of which occurred outside the intensive care unit setting. A significant decrease in incidence was observed among patients with leukemia over the study period, together with a relative decrease in Candida albicans and Candida tropicalis infections and an increase in Candida krusei and possibly Candida glabrata infections. In the multivariate analysis, fluconazole prophylaxis provided strong protection against the development of C. tropicalis infection (odds ratio [OR] = 0.08) and C. albicans infection (OR = 0.15), in comparison with protection against infections due to other species, but it was the single most important determinant for the relative increase in C. krusei (OR = 27.07) and C. glabrata (OR = 5.08) infections. In conclusion, there has been a substantial shift in the epidemiology of hematogenous candidiasis caused by different Candida species in recent years. Fluconazole appears to be playing a major role in this observed shift.
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PMID:The epidemiology of hematogenous candidiasis caused by different Candida species. 967 96

Effective prophylaxis against fungal infection is important in neutropenic patients with hematologic malignancies, but the best method remains unclear. We investigated the effectiveness of fungal prophylaxis with amphotericin B or fluconazole. We reviewed the data on fungal isolates, plasma (1-->3)-beta-D glucan (beta-D glucan) levels, febrile periods (the number of days with an axillary temperature > 38 degrees C), and the duration of an axillary temperature > 38 degrees C when the neutrophil count was < 500/microliter. Of the 124 patients studied, 57 had acute myelogenous leukemia, 19 had acute lymphoblastic leukemia, 18 had non-Hodgkin's lymphoma, six had chronic myeloid leukemia, three had adult T-cell leukemia, and five had chronic lymphocytic leukemia. There were no significant differences in clinical characteristics between the 70 patients treated with amphotericin B and the 54 patients given fluconazole. There was a significant decrease of fungal isolates (chi 2-test, p < 0.001), the plasma beta-D glucan level (Wilcoxon test, p = 0.0001), and the febrile period (t-test, p < 0.05) in the patients given fluconazole compared with those given amphotericin B. In neutropenic patients with hematologic malignancies, prophylaxis with fluconazole significantly decreased fungal isolation and other indicators of fungal infection when compared with amphotericin B. Fluconazole may therefore be more effective for fungal prophylaxis in these patients.
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PMID:Fluconazole versus amphotericin B for the prevention of fungal infection in neutropenic patients with hematologic malignancy. 1044 77

Fungal colonization profiles from four different anatomical sites were evaluated in 266 neutropenic cancer patients receiving intensive cytotoxic therapy for acute leukaemia or for autologous marrow transplantation. At the beginning of chemotherapy patients were allocated randomly to receive oral fluconazole 400 mg daily or an identical placebo until prophylaxis failure or marrow recovery. Candida albicans colonization was reduced from 30 to 10% in the fluconazole recipients while it increased from 32 to 57% in the placebo patients (P<0.001). By the end of prophylaxis, colonization with non-albicans Candida species increased from 7 to 21% and 8 to 18% in the fluconazole and placebo patients, respectively (P = 0.396). Although Candida glabrata was isolated more frequently at the end of the prophylactic period in the fluconazole patients than in the placebo patients (16 versus 7%), only one definite invasive C. glabrata infection was noted. Overall, definite invasive fungal infections were documented in 26 patients [four fluconazole versus 22 placebo patients (P< or =0.001)]. In 23 (92%) patients the infections were caused by persistently colonizing or newly acquired organisms. While probable invasive fungal infections were noted in five fluconazole patients, 10 placebo patients were also affected (P = 0.19). An end-of-prophylaxis colonization index >0.25 was 76% sensitive but only 69% specific for invasive fungal infection. However, a colonization index < or =0.25 at baseline had a negative predictive value of 88% for development of invasive fungal infection. Fluconazole prophylaxis decreased colonization by fungi and subsequent invasive fungal infections in neutropenic cancer patients.
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PMID:Impact of fluconazole prophylaxis on fungal colonization and infection rates in neutropenic patients. The Canadian Fluconazole Study. 1110 22


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