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)

Fusariosis, a rare infectious disease of the immunocompromised host, is relatively resistant to amphotericin B (AmB) or other antifungal agents. We describe a 5-year follow-up of a 40 year old woman with T-type acute lymphoblastic leukemia who following chemotherapy developed prolonged high fever, chills, night sweats, and severe weakness. Liver function tests were impaired and abdominal computerized tomography (CT) showed multiple lesions in the liver and abnormal structure of the spleen. A laparotomy revealed multiple granulomas containing Fusarium sp. in the liver, and the spleen was heavily infiltrated by the same fungus. The patient failed to respond to the conventional AmB dosage form (Fungizone) even after a total dose of 3.0 g was given, and developed significant renal impairment. AmB was complexed (in a mole ratio of 1:16) with a mixture of the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (mixed in 7:3 mole ratio). The resulting drug complex, AmB-PLC, was then administered (1-4 mg/kg/day, total dose 4.2 g) and subsequently the patient was cured of all symptoms of fusariosis. There were only mild side effects and no nephrotoxicity was evident. On the contrary, marked improvement of the renal function tests occurred during AmB-PLC treatment. Eight months later, she developed a spinal lesion with dense consistency in L5 and S1, and after receiving another course of AmB-PLC (3.1 g) she recovered completely. In a 2 year follow-up period the patient had no further relapse of the fungal disease. Subsequent chemotherapy given for relapse of the leukemia was followed by a new fungal infection, which was treated with AmB-cholesteryl sulfate complex (Amphocil).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disseminated visceral fusariosis treated with amphotericin B-phospholipid complex. 834 74

The Authors report a case history of rhinocerebral mucormycosis in a patient with chronic lymphatic leukaemia and recommend that therapy be based on three different approaches: treatment for the underlying disease, systematic antifungal treatment with Amphotericine B, and surgical asportation of diseased tissue. They affirm that results may be surprisingly successful, even in cases with signs of orbital-cerebral involvement which are indicative of a poor prognosis and the concomitant presence of a serous disease such as leukaemia.
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PMID:[Rhinocerebral mucormycosis: a case report]. 856 Oct 25

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

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

A case of disseminated invasive fusarial infection (DFI) with sinus involvement in a patient with acute myeloblastic leukaemia is reported. Amphotericin B with rifampin were administrated and wide radical sinus surgery was performed. Nevertheless, the patient died six weeks later. The four principal forms of fusarial infections in humans are discussed: toxicosis, allergic fungal sinusitis, locally invasive infection, and disseminated invasive infection. Prognosis of DFI in the immunocompromised host is usually poor, and treatment is difficult. Profound and prolonged neutropaenia appears to be the major predisposing factor. The literature on infections caused by Fusarium species in immunocompromised hosts is reviewed, especially those where the sinuses were involved.
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PMID:Lethal disseminated Fusarium infection with sinus involvement in the immunocompromised host: case report and review of the literature. 905 Jan 4

When long-term bone marrow cultures are treated with Amphotericin B (AB) their haemopoietic stem cells (HSC) cease growing. This is not a toxic effect of the drug because once that is removed, HSC resume clonal growth and, given sufficient time, form as many cells as HSC in untreated cultures. Amphotericin B-evoked inhibition of blood formation is probably mediated by transmembrane communication between HSC and stroma for the following reasons: (1) AB does not stop HSC forming colony-forming units in culture (CFU-c) when HSC are separated from stroma by culturing them on Transwell inserts above the stroma. (2) Conditioned media (CM) from AB-containing or normal long-term cultures (LTC) does not inhibit normal marrow cells forming colonies in semi-solid cultures without stromal underlays. (3) AB itself does not stop bone marrow cells forming colonies in semi-solid cultures nor does it stop stromal cells growing or prejudice their long-term maintenance. (4) Furthermore, growing stromal cells with AB does not alter the number of transcripts they form for cytokines and chemokines to any large extent, including TGF-beta1. We have extensive, though circumstantial, evidence that gap junctions are involved in this communication. AB only stopped the growth of HSC when we blocked intercellular communication via gap junctions (GJIC) (tested by micro-injection of lucifer yellow). Lipophilic compounds that do not affect GJIC had no effect on the growth of HSC. Looking at a series of stromal cell lines from foetal liver and neonatal bone marrow we found that extensive GJIC correlated with stromal support of the late-appearing clones formed by primitive HSC (week 3-5 cobblestone-area forming cells, CAFC). We propose that the proliferation of HSC is regulated via transmembrane communication between stromal and HSC. Our findings support the proposal that gap junctions play a part in this stromal-dependent regulation.
Leukemia 1997 Aug
PMID:Does transmembrane communication through gap junctions enable stem cells to overcome stromal inhibition? 926 82

This study evaluated the efficacy of low-dose dopamine for prevention of amphotericin B-induced nephrotoxicity in autologous bone marrow transplant and leukemia patients. Seventy-one patients undergoing cytoreductive therapy who required amphotericin B were randomly assigned in an unblinded fashion to a group receiving continuous-infusion low-dose dopamine (3 microgram/kg/min) or a group receiving no dopamine. Amphotericin B was dosed at 0.5 or 1.0 mg/kg/day based on computerized tomography scan results or presence of positive blood cultures. No patient received saline boluses. The rate of nephrotoxicity, severity as graded by Southwest Oncology Group toxicity criteria, and time to each grade of nephrotoxicity were compared between the two groups. Eighty percent of the no-dopamine group and 66.7% of the dopamine group developed nephrotoxicity, defined as a 1.5-fold or greater increase in baseline serum creatinine level (P = 0.20). No statistical difference was noted at any grade of nephrotoxicity between the two groups. Thirty-four percent of patients in the no-dopamine group versus 17.6% in the dopamine group had a 2.5-fold or greater increase in serum creatinine level, which was not statistically significant (P = 0.0888). Ten patients developed grade IV nephrotoxicity and were withdrawn from the study, 7 in the no-dopamine group and 3 in the dopamine group (P = 0.19). The time to each grade of nephrotoxicity was also not significantly different for the two groups. Eleven adverse drug reactions were reported in the dopamine group in comparison to one in the no-dopamine group. Thus, dopamine offers little in the way of prevention of nephrotoxicity associated with amphotericin B therapy. Although the significance of drug reactions in the dopamine group is not clearly established due to lack of cardiac monitoring in the no-dopamine group, dopamine therapy is not without complications.
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PMID:Efficacy of low-dose dopamine in preventing amphotericin B nephrotoxicity in bone marrow transplant patients and leukemia patients. 983 98

A retrospective study of 23 patients with acute leukaemia and hepatosplenic candidiasis (HSC) was conducted to evaluate clinical treatment characteristics in terms of amount and duration of antifungal agents and to assess treatment outcome. Patients were admitted to two major tertiary care centres between 1990 and 1998. The diagnosis of HSC was based on clinical, blood cultures, histologic and imaging studies. Patients were treated with amphotericin B without interruption of the planned chemotherapy regimens. Serial magnetic resonance imaging (MRI) studies were the main tool for following patients' response and activity of the fungal lesions in conjunction with clinical and laboratory parameters. Treatment with amphotericin B was continued until resolution of all clinical symptoms and signs attributable to HSC, obtaining negative blood cultures and the appearance of at least healed lesions on MRI. Amphotericin B was discontinued in four patients because of severe nephrotoxicity (two patients), or continuous fever and persistent fungal lesions on MRI (two patients). Amphotericin B lipid complex (ABELCET) was successfully used as salvage therapy for these refractory patients. Four patients died with evidence of HSC despite treatment and supportive measures. The response rate for treatment of HSC was 82%. The mean total dose of amphotericin B including empirical treatment was 4 g and the median duration of treatment for responding patients was 112 d. The median number of days of anti- fungal treatment before the disappearance of fever was 19 d. Our results confirmed the need for protracted courses of antifungal agents for the successful eradication of HSC. Chemotherapy for the underlying disorder should not be interrupted or delayed in order to treat HSC.
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PMID:Hepatosplenic candidiasis in patients with acute leukaemia. 1088 25

Patients with haematological malignancies form one of the most susceptible host groups for microbial infection, especially during neutropenia. The incidence of invasive fungal infections has increased in recent years, highlighting the need for better diagnosis and more effective antifungal therapies. Amphotericin B is the drug of choice for many fungal infections, although toxicity and the need for intravenous infusion restrict its use. When possible, oral administration of antifungal agents is preferable but intravenous administration is often needed and current oral agents have their limitations: fluconazole because of a narrow spectrum of activity; itraconazole capsules because of erratic absorption. In this review, prophylactic and treatment options for systemic fungal infections are discussed. The specific needs of patients with different types of leukaemia and the benefits of new amphotericin B and itraconazole formulations are examined.
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PMID:Prophylaxis and treatment of fungal infections associated with haematological malignancies. 1092 37

A 7-y-old boy with relapsed acute lymphatic leukaemia developed fungaemia due to Acremonium strictum, a fungus belonging to the group of the hyaline hyphomycetes. Initially, the fungus was misdiagnosed as Candida sp. due to the presence of abundant adventitious forms. At the time of diagnosis the patient was neutropenic and had a central venous catheter (CVC) in situ. The formation of an occlusive thrombotic mass in the v. subclavia dextra complicated the infection. Treatment consisted of amphotericin B, fluconazole, granulocyte colony-stimulating factor (G-CSF) and removal of the CVC. However the patient responded clinically only after the intravascular thrombus had been removed surgically. Amphotericin B, voriconazole and terbinafine showed high activity in vitro against the Acremonium isolate. A literature review revealed 5 other immunocompromised paediatric patients with a systemic or localized infection due to Acremonium spp.
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PMID:Acremonium strictum fungaemia in a paediatric patient with acute leukaemia. 1095 64


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