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)

We investigated the correlation between trough cyclosporine concentration in plasma measured by polyclonal fluorescence polarization immunoassay (FPIA) and polyclonal radioimmunoassay (RIA) or in whole blood measured by high-performance liquid chromatography (HPLC) and the risk of renal dysfunction or acute graft-versus-host disease in 29 patients undergoing allogeneic bone marrow transplantation for leukemia. The FPIA and RIA values were highly correlated (r = 0.93) and on the average CsA concentrations measured by FPIA were 1.56 times higher than those measured by RIA. Ten patients developed renal dysfunction and 10 developed grades II-IV acute GVHD. Although univariate analysis showed that plasma CsA concentrations measured by either FPIA or RIA were significantly correlated with renal dysfunction, the association was stronger with FPIA. Plasma CsA concentrations measured by FPIA but not RIA remained a significant risk factor for renal dysfunction in a multivariate relative risk model. Amphotericin therapy was significantly associated with renal dysfunction in the univariate analysis but not in the multivariate analysis. No significant associations were found between whole blood CsA or CsA M1 concentration, patients' age, gender, or CsA dose and the risk of renal dysfunction. None of the covariates analyzed significantly correlated with the development of acute GVHD. These data suggest that plasma CsA concentrations measured by nonspecific assays may more accurately correlate with renal dysfunction than whole-blood CsA concentrations measured by HPLC in marrow transplant recipients.
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PMID:Pharmacodynamic studies of cyclosporine in marrow transplant recipients. A comparison of three assay methods. 160 84

Granulocytopenia is the single most important risk factor for infection in patients with acute leukaemia. There are limitations to the effective prophylaxis of infection in granulocytopenic patients, but practical measures include the management of the patient in a private hospital room, the requirement of all medical personnel and visitors to wash their hands carefully and to wear masks, restricting the patient to a low-bacteria diet devoid of fresh fruit, vegetables and salads, and the administration of oral antimicrobial agents for gastrointestinal decontamination. When fever develops, empirical therapy with a combination of an aminoglycoside plus an antipseudomonal beta-lactam should be started promptly. A double beta-lactam combination of cefoperazone or ceftazidime plus piperacillin can be substituted if nephrotoxicity is a concern. The addition of empirical intravenous amphotericin may be useful in patients who remain febrile and granulocytopenic on broad-spectrum antibiotics, especially if surveillance cultures indicate fungal colonization. Amphotericin is also the most reliable agent for the treatment of established fungal infections. Acyclovir is not recommended for prophylaxis in acute leukaemia patients but should be reserved for the treatment of well-documented and clinically significant herpes simplex viral infections. During periods of remission, most patients with AML remain free of infection except when they become granulocytopenic again during intensification or consolidation chemotherapy. On the other hand, children with ALL in remission may experience frequent infections unrelated to granulocytopenia as a consequence of their maintenance chemotherapy. Pneumocystis carinii, varicella zoster, and other viruses are common pathogens. Trimethoprim-sulphamethoxazole is effective prophylaxis against Pneumocystis carinii pneumonia in patients with ALL, while intravenous acyclovir is the drug of choice for treatment of varicella zoster infection. Transfusion therapy in the acute leukaemia patient is guided by the patient's peripheral blood counts and degree of sensitization to blood products. Generally, packed red blood cells are given in order to maintain the haematocrit at greater than 30%, while random-donor platelets are administered to keep the platelet count at greater than 20 X 10(9)/l. If refractoriness to platelet transfusions develops, HLA-matched platelets from family members or selected unrelated donors can be used. Similarly, washed or filtered red blood cells may be given to patients with previous and recurrent non-haemolytic febrile reactions to red blood cell transfusions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Infection and transfusion therapy in acute leukaemia. 309 21

Cyclosporin-A (CsA) was given to 22 patients who received allogeneic bone marrow transplants as therapy for aplastic anemia and hematologic malignancies. The drug was given daily for 180 days starting with the day of marrow infusion. Engraftment was not impaired and myelotoxicity was not observed. Cutaneous graft-versus-host disease (GVHD) developed in five patients and all either spontaneously resolved or promptly responded to therapy with steroids. Five patients developed systemic GVHD and all responded to therapy with steroids, but only two survived. Interstitial pneumonia was seen in six patients and was fatal in all of them. Liver function abnormalities were seen in 14 patients but could not positively be correlated with CsA administration. Renal function abnormalities were seen in 17 patients. Amphotericin-B therapy contributed significantly to the renal failure. Serum levels of CsA, measured by radioimmunoassay, could not be correlated with the presence of liver or renal function abnormalities. Overall survival so far has been 50.0%. Second malignancies were not observed, but one patient relapsed with leukemia at 343 days.
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PMID:Cyclosporin-A to prevent graft-versus-host disease: a pilot study in 22 patients receiving allogeneic marrow transplants. 633 59

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

Encapsulating amphotericin B (AmB) into liposomes or binding of AmB to other lipid carriers results in a significant reduction of toxicity of AmB and possibly an increased therapeutic index. Following promising clinical results with investigational formulations, three industrial compounds have been developed: AmBisome, Amphocil (Amphotericin B Colloidal Dispersion) and Amphotericin B Lipid Complex (ABLC, Abelcet). These three formulations differ significantly in composition and pharmacokinetics. AmB serum levels after ABLC and Amphocil administration are low, but after AmBisome much higher. However, the interpretation of the pharmacokinetic data is hampered by the inability to separate free AmB fractions from tissue-, protein- and lipid carrier bound fractions. All three compounds share a considerable reduction of nephrotoxicity. However, the acute reaction rates differ among these compounds. Amphocil showing the highest and AmBisome the lowest rate. Unfortunately, efficacy data of ongoing trials comparing these formulations with conventional AmB are scarce. Therefore, for the moment we can recommend these compounds only in cases of intolerance to or failure on AmB therapy. The optimal therapeutic dosages have not been established, but dosages as low as 1 mg/kg should be avoided in the initial treatment of fulminant fungal infections, since efficacy may be inferior to equal doses of conventional AmB.
Leukemia 1996 Jun
PMID:Liposomal and lipid-based formulations of amphotericin B. 864 62

A prospective study was performed to compare the infusion-associated toxicity of three different amphotericin B preparations and to correlate acute side-effects with plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1-RA) during and after the infusions. Six adult neutropenic patients with acute leukaemia suffering from suspected or documented systemic fungal infections were treated on three consecutive days with conventional amphotericin B (AmB), liposomal AmB (AmBisome) and AmB mixed in lipid emulsion (AmB/lipid). Drugs were given over 1-2 h. Drug-induced toxicity was monitored every 30 min for 4 h. Plasma levels of the three cytokines were determined using commercially available enzyme-linked immunosorbent assay (ELISA) techniques. Four of six patients showed toxicity after AmB and AmB/lipid infusions; only one patient reacted to liposomal AmB. Clinical toxicity was associated with increases in TNF-alpha plasma levels during two of four infusions of AmB and three of four infusions of AmB/lipid. Major increases in IL-6 occurred during three of four infusions of AmB and during all four AmB/lipid infusions associated with clinical toxicity. Three of four AmB infusions and all four AmB/lipid infusions accompanied by clinical toxicity were associated with major increases in IL-1-RA plasma concentrations. Liposomal AmB was better tolerated than AmB and AmB/lipid. This formulation also caused the lowest liberation of all three cytokines tested. The severity of clinical symptoms did not correlate closely with absolute cytokine plasma levels. The findings provide further evidence that expression of TNF-alpha, IL-6 and IL-1-RA plays an important role in mediating AmB-related acute toxicity in vivo.
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PMID:Infusion-related toxicity of three different amphotericin B formulations and its relation to cytokine plasma levels. 872 Jan 96

Despite its considerable toxicity, amphotericin B (AmB) remains the 'golden standard' in the treatment of many systemic fungal infections. To reduce this toxicity, with the aim of increasing its therapeutic index, AmB can be encapsulated into liposomes or bound to lipid carriers. Following promising clinical results with investigational formulations, three industrial compounds are available at this moment: Abelcet (Amphotericin B Lipid Complex, ABLC), Amphocil (Amphotericin B Colloidal Dispersion) and AmBisome. These three formulations differ significantly in composition and pharmacokinetics. All three compounds share a considerable reduction of nephrotoxicity, but the number of acute reactions differ among these compounds, Amphocil showing the highest and AmBisome the lowest rate. Increased therapeutic indexes for all three formulations were shown only in some of the animal models for several fungal infections. Four recent clinical trials comparing these formulations with AmB demonstrated their clinical efficacy but failed to clearly show an increased therapeutic index. Therefore these compounds can be recommended in cases of intolerance to or failure on AmB therapy. The optimal therapeutic dosages have not been established, but dosages as low as 1 mg/kg should probably be avoided in the initial treatment of fulminant fungal infections, since efficacy may be inferior to equal dosages of conventional AmB.
Leukemia 1996 Oct
PMID:The use of lipid formulations of amphotericin B for systemic fungal infections. 884 91

Platelet transfusion support is required during bone marrow aplasia following ablative chemotherapy and bone marrow progenitor cell transplantation (BMT). Amphotericin-B is frequently given to these patients, both therapeutically and prophylactically, and has been described to have a negative impact on the results of platelet transfusions. We conducted a prospective study of the effect of amphotericin-B on transfused platelet recovery and survival in 81 BMT or acute leukaemia patients. One hundred and ninety-five platelet transfusions administered to 81 consecutive patients were analysed. The platelets were transfused 2 h after the completion of amphotericin-B. Using this schedule resulted in no effect of amphotericin-B on platelet recovery or survival, although platelet increments were modestly depressed in patients receiving high- vs. low-dose amphotericin-B. We conclude that the timing of amphotericin-B infusion be evaluated in patients demonstrating poor platelet recovery and survival. Transfusing platelets at least 2 h after the completion of amphotericin-B decreases the detrimental effect of this antifungal agent on transfused platelet recovery and survival.
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PMID:Transfusing platelets 2 h after the completion of amphotericin-B decreases its detrimental effect on transfused platelet recovery and survival. 956 59

Fungal infections remain a major cause of treatment failure and death in acute leukemia. New liposomal preparations of amphotericin B are now available. While less toxic, their comparative efficacy and toxicity profiles are unknown. In this study the comparative efficacy and safety of ABLC vs. AmBisome was evaluated in seventy-five patients with leukemia who developed 82 episodes of suspected or documented mycosis, and were treated (1:1) with either ABLC (n=43) or AmBisome (n=39). Both drugs were dosed accordingly from 3 to 5 mg/kg/day. Using an intent-to-treat analysis, the overall response to therapy was 27/43 (63%) for ABLC and 15/39 (39%) for AmBisome (p=0.03). Median dose and duration of treatment was 10 days at 3 mg/kg for ABLC and 15 days at 4 mg/kg for AmBisome. Acute, not dose-limiting infusion side effects were seen in 70% vs. 36% (p=0.002), ABLC vs. AmBisome. Increase of bilirubin > 1.5 times from baseline was 38% vs. 59%, ABLC vs. AmBisome (p=0.05). ABLC and AmBisome were equally effective for the treatment of suspected or documented fungal infections. While, acute infusion-toxicity was greater with ABLC, infusion toxicity requiring discontinuation was similar for both drugs. AmBisome was better tolerated than ABLC but was associated with mild abnormalities in liver function tests at the end of therapy.
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PMID:Comparison of amphotericin B lipid complex (ABLC) vs. ambisome in the treatment of suspected or documented fungal infections in patients with leukemia. 1142 24

A 52-year-old man was admitted for treatment of hypoplastic leukemia (M 1). After induction chemotherapy with IDR and AraC, the patient developed prolonged febrile neutropenia, and a diagnosis of invasive pulmonary aspergillosis was made. We started administration of AMPH-B and G-CSF, but the patient showed no clinical improvement. M-CSF was added to the regimen, and this led to an increase in the white blood cell count with resolution of pneumonia. It is suggested that administration of M-CSF with antibiotics and G-CSF may be beneficial for treating acute leukemia patients with prolonged febrile neutropenia after intensive chemotherapy.
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PMID:[Successful treatment of invasive pulmonary aspergillosis with G-CSF and M-CSF during long-term bone marrow suppression in hypoplastic leukemia]. 1197 51


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