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

Fungal infections are a leading cause of mortality in patients with neutropenia. Candidiasis and aspergillosis account for most invasive fungal infections. General prophylactic measures include strict hygiene and environmental measures. Haemopoietic growth factors shorten the duration of neutropenia and thus may reduce the incidence of fungal infections. Fluconazole is appropriate for antifungal prophylaxis and should be offered to patients with prolonged neutropenia, such as high-risk patients with leukaemia undergoing remission induction or consolidation therapy and high-risk stem cell transplant recipients. Empirical antifungal therapy is mandatory in patients with persistent febrile neutropenia who fail to respond to broad-spectrum antibacterials. Intravenous amphotericin B at a daily dose of 0.6 to 1 mg/kg is preferred whenever aspergillosis cannot be ruled out. Lipid formulations of amphotericin B have demonstrated similar efficacy and are much better tolerated. Fluconazole is the best choice for acute candidiasis in stable patients; amphotericin B should be used in patients with unstable disease. Use of fluconazole is restricted by the existence of resistant strains (Candida krusei and, to a lesser extent, C. glabrata). Amphotericin B still remains the gold standard for invasive aspergillosis. Lipid formulations of amphotericin B are effective in aspergillosis and because they are less nephrotoxic are indicated in patients with poor renal function. Itraconazole is an alternative in patients who have good intestinal function and are able to eat. Mucormycosis, trichosporonosis, fusariosis and cryptococcosis are less common but require specific management. New antifungal agents, especially new azoles, are under development. Their broad in vitro spectrum and preliminary clinical results are promising.
 ...
PMID:Fungal infections in patients with neutropenia: challenges in prophylaxis and treatment. 1119 Apr 15

Multidrug resistance due to overexpression of P-glycoprotein (Pgp) leads to reduced intracellular drug accumulation and makes the cells resistant to chemotherapy. In this study we focused on how drugs used in the supportive care of acute myeloid leukemia (AML) patients interfere with Pgp. The effect on intracellular accumulation of the fluorescent dye Rhodamine 123 (Rh 123) was studied in the human promyelocytic leukemia cell line HL-60 and two anthracycline resistant, Pgp expressing, sublines. Each drug was used at two different concentrations: plasma peak concentration and half the plasma peak concentration. Drugs which increased the Rh 123 uptake by > 10% were included in the second part of the study where the cytotoxic effect was tested in combination with daunorubicin. In the Rhodamine assay none of the tested drugs had any significant effect on the Rh 123 efflux in the resistant cell lines. Amphotericin B, cefuroxime, erythromycin and dixyrazin had minor effects on Rh 123 uptake but showed a significant additive effect to the toxicity of daunorubicin suggesting other mechanisms of action than reversal of Pgp. In conclusion this in vitro model where Rh 123 uptake was studied in an anthracycline resistant leukemia cell line could not demonstrate any significant interactions with Pgp for the tested drugs.
 ...
PMID:Interactions between P-glycoprotein and drugs used in the supportive care of acute myeloid leukemia patients. 1169 5

A 54-year-old woman undergoing chemotherapy for acute myeloid leukemia developed invasive pulmonary mucormycosis in the right upper lobe at the neutropenic nadir. Amphotericin B therapy became ineffective after an abscess formed in the affected lung, and insufficient infection control compelled us to interrupt chemotherapy. The lesion was suspected of invading the anterior chest wall. After right upper lobectomy combined with the anterior chest wall resection, the chest wall defect was reconstructed using autologous free rib grafts. Successful control of the fungal infection by resection enabled us to restart chemotherapy with concomitant use of Amphotericin B. In selected cases of leukemia-associated pulmonary mucormycosis refractory to Amphotericin B therapy, aggressive surgical intervention may facilitate anti-leukemia chemotherapy and prolong survival.
 ...
PMID:Pulmonary resection with chest wall removal and reconstruction for invasive pulmonary mucormycosis during antileukemia chemotherapy. 1272 89

We report the findings of a questionnaire distributed by the Committee of Supportive Care of the Japan Adult Leukemia Study Group to 196 hospitals throughout Japan. For antimicrobial prophylaxis, the oral quinolones are prescribed by 38% of physicians and polymixin B by 31%. For antifungal prophylaxis, amphotericin B is prescribed by 42% of physicians and fluconazole by 41%. Febrile neutropenia is empirically treated with cephalosporin or carbapenem monotherapy by 35% of physicians. Overall, dual therapy (i.e., an aminoglycoside plus a cephalosporin, a carbapenem, or an antipseudomonal penicillin) is prescribed by 50% of physicians. When response to initial empirical therapy does not occur after 3-4 days, 51% of physicians add an antifungal agent; fluconazole is preferred to amphotericin B (prescribed by 66% vs. 28% of physicians). For the treatment of fungemia due to Candida albicans, fluconazole was prescribed by 59% of physicians in cases of stable disease and amphotericin B was prescribed by 57% of physicians in cases of unstable disease. Amphotericin B is selected to treat invasive aspergillosis, but a dose of 0.5-0.7 mg/kg, inadequate for this disease, is prescribed by 44% of physicians. Granulocyte colony-stimulating factor is prescribed to treat patients with acute myelogenous leukemia who have life-threatening infections (27% of physicians) or who have clinically or microbiologically documented infections (26% of physicians).
 ...
PMID:Current antimicrobial usage for the management of infections in leukemic patients in Japan: results of a survey. 1525 15

Geotrichum capitatum, now known as Blastoschizomyces capitatus, can be responsible for several opportunistic infections (systemic infection or localized at lungs, liver, kidney, encephalitis or meningitis) in an immunocompromised host, especially in those patients affected by leukaemia or under immunosuppressive therapies. A 66-year-old woman with polimyosite under steroid and immunosuppressant therapy was hospitalized in ICU for an acute respiratory distress with moderate hypoxaemia and normocapnia. Pulmonary X-ray revealed a bilateral pneumonia. Hypoxaemia became severe 48 hours later and the patient underwent mechanical ventilation and empirical antibiotic therapy. Blood cultures, urine cultures and serological tests were negative, while yeast was identified by Gram's stain of bronchoaspirate. Before identifying the yeasts Fluconazole was added to therapy. At day 5 the clinical conditions remained severe and Candida spp were excluded: so Fluconazole was switched to liposomal Amphotericin B. At day 8 B. capitatus was identified. At day 26 the patient died of refractory respiratory insufficiency. B. capitatus infection is infrequent and its prognosis is severe, with a high mortality rate (>50%). Microbiological diagnosis requires time to characterize the yeast. At present no standard therapy is available although some authors report a good susceptibility to Amphotericin B and Voriconazole (100%), according to NCCLS guidelines.
 ...
PMID:[Pulmonary infection caused by Blastoschizomices capitatus]. 1639 22

Leukemia and lymphoma cells are much more sensitive to Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) than normal pluripotent hematopoietic stem cells and normal colony forming unit-granulocyte/macrophage progenitors (CFU-GM). By contrast, most solid tumor cells are only moderately sensitive to MC540-PDT. The limited activity against solid tumor cells has detracted from MC540's appeal as a broad-spectrum purging agent. We report here that noncytotoxic concentrations of amifostine (Ethyol, Ethiofos, WR-2721) and amphotericin B used either alone or in combination potentiate the MC540-sensitized photoinactivation of leukemia cells, wild-type small cell lung cancer cells and cisplatin-resistant small cell lung cancer cells. Amphotericin B also enhances the MC540-sensitized photoinactivation of normal CFU-GM, whereas amifostine protects CFU-GM against the cytotoxic action of MC540-PDT. The yield of CD34-positive normal hematopoietic stem and progenitor cells is only minimally diminished by pretreatment with amifostine, amphotericin B or combinations of amifostine plus amphotericin B. Purging protocols that combine MC540-PDT with amifostine or with amifostine plus amphotericin B could offer a simple and effective approach to the purging of autologous stem cell grafts that are contaminated with solid tumor cells or the purging of stem cell grafts from heavily pretreated leukemia patients that contain reduced numbers of normal stem and progenitor cells and, therefore, can ill afford additional losses caused by purging.
 ...
PMID:Potentiation of the antitumor effect of Merocyanine 540-mediated photodynamic therapy by amifostine and amphotericin B. 1661 99

A 46-year-old previously healthy woman was diagnosed with acute lymphoblastic leukaemia. The induction phase was complicated by alpha-haemolytic streptococcal bacteremia which responded to antibacterial therapy. Subsequently, the patient developed pneumonie due to Chlamydiapneumoniae which responded to macrolides. Following this infection the patient developed recurrent fever and new pulmonary infiltrates were noted. Bronchoscopy was performed and treatment was administered with liposomal amphotericin B (L-AmB, AmBisome) for two days, but was complicated by acute renal failure. Aspergillus fumigatus was cultured from bronchoalveolar lavage fluid [corrected] L-AmB was discontinued and voriconazole and caspofungin were administered. Despite aggressive antifungal therapy the patient developed progressive invasive infection, with central nervous system involvement as well as lesions appearing in the kidneys and liver. The patient died one week following the diagnosis of aspergillosis.
 ...
PMID:Disseminated invasive aspergillosis in a patient with acute leukaemia. 1691 60

Among patients with haematologic disorders, mucormycosis most commonly occurs in those with acute leukaemia or lymphoma who have developed neutropenia due to malignancy or to chemotherapy, and in transplanted patients receiving immunosuppressive treatment. Here, we aim to present a retrospective study conducted over a 5-year period (2001-2005). The study included 20 patients with haematologic malignancies with a proven mucormycosis admitted in Medical Oncology Divisions in Cukurova University Hospital. The most frequent sites of infection were paranasal sinuses (95%) and lung (5%). Antifungal treatment was empirically administered in 18 (90%) patients; 18 patients underwent radical surgical debridement (90%). The therapy was successful for only eight patients (40%). Eleven patients died within 1 months of the diagnosis of fungal infection: the cause of death was only by mucormycosis in four patients (36.6%), mucormucosis and systematic inflamatuar response syndrome (SIRS) in two patients (18.2%) and progression of haematologic disease in five patients (45.5%). At univariate analysis, the factors that correlated with a positive outcome from infection were the following: amphotericin B treatment, neutrophil recovery from postchemotherapy aplasia. At multivariate analysis, the factors that significantly correlated with recovery from infection were the liposomal amphotericin B treatment (p = 0.026), doses of L-AmB (p = 0.008) and the length of the treatment (p = 0.01), respectively. It seems to have increased in recent years. Although a reduction of mortality has been observed recently, the mortality rate still remains high. Extensive and aggressive diagnostic and therapeutic procedures are essential to improve the prognosis in these patients.
 ...
PMID:Mucormycosis-associated fungal infections in patients with haematologic malignancies. 1736 81

A 5-year-old boy had a 10-month remission of acute lymphocytic leukemia (ALL) after chemotherapy. Re-induction chemotherapy was performed for relapse of ALL. Thereafter, he suffered from an episode of neutropenic fever with pneumonia. One week following control of the condition with antibiotics, a 1 x 1-cm, red, painful nodule appeared on the left thigh, which was initially suspected to be Pseudomonas infection. Parenteral ceftazidime and amikacin were administered, but persistent high fever, mild cough, and a few painful erythematous papulonodules on the face and lower extremities appeared several days later (Fig. 1). These lesions increased insidiously in diameter up to 2-5 cm with central necrosis. Hemogram showed neutropenia with a shift to the left [white blood cell (WBC) count, 2.1 x 10(9)/L; neutrophil count, 0.21 x 10(9)/L]. A skin biopsy showed heavy growth of hyaline branching septate hyphae in the deep dermis and subcutis, together with fat necrosis (Fig. 2). Invasion of molds into vessels and sweat glands was also seen. A culture from a lesion yielded Fusarium moniliforme, but no fungi were isolated from blood specimens. Only mild infiltrations on bilateral lower lung fields were detected by chest roentgenography. The skin lesions gradually healed and the fever subsided 2 weeks after the initiation of therapy with amphotericin B 30 mg and itraconazole 200 mg daily. Meanwhile, relapse of leukemia was detected by hemogram showing atypical leukocytosis (WBC count of 24,400 x 10(9)/L, with blast cells representing 78%). A course of chemotherapy with cytarabine, mitoxantrone, and VP-16 was prescribed, subsequently resulting in neutropenia (WBC count, < 0.1 x 10(9)/L; neutrophil count, 0/L) and spiking fever. Although the aforementioned antifungal therapy was continued, the centers of the originally healed lesions turned dusky red, swollen, necrotic, and ulcerative. There were more than 10 such ecthymiform lesions. After administration for 22 days, itraconazole was discontinued because of no appreciable effects. Granulocyte colony-stimulating factor (G-CSF) salvage was used, and the neutropenia gradually subsided 20 days later. In addition, the ecthymiform lesions gradually resolved. Amphotericin B was discontinued 1 week following neutrophil recovery. The patient died of Acinetobacter baumannii and Stenotrophomonas maltophilia sepsis 8 months later.
 ...
PMID:Disseminated cutaneous Fusarium moniliforme infections in a leukemic child. 1747 77

With its broad spectrum of activity and better tolerability profile than conventional amphotericin B, liposomal amphotericin B (L-AmB) may be the drug of choice for antifungal prophylaxis in haematological patients. An open-label, multicentre, prospective, pilot study was conducted in adult patients receiving chemotherapy for acute leukaemia (AL) or myeloablative allogeneic stem cell transplantation (SCT). Patients received weekly 10mg/kg infusions of L-AmB for 4 weeks for AL and 8 weeks for SCT. The primary objective was safety, with particular attention to infusion-related reactions and nephrotoxicity. Twenty-nine adult patients were included: 21 AL (median age 52 years) and 8 SCT (median age 37 years). The most frequent adverse events (AEs) related to study drug were infusion-related reactions, 12 of which (from a total of 76 infusions) led to increased infusion duration for better tolerance. No AE related to the study drug led to discontinuation of prophylactic treatment in AL patients. In SCT patients, eight AEs (in six patients) reported to be related to study treatment led to treatment discontinuation. Enrolment was discontinued in the SCT group as recommended by the independent data review committee in accordance with the 10% limit of AEs (CTC grade 3-4) fixed by the protocol. The appropriate timing of high-dose prophylactic L-AmB remains to be determined in the SCT setting to optimise the safety profile of this regimen. For AL, a 10mg/kg weekly dose appears to be well tolerated during chemotherapy and may represent an important tool towards improving AL patient outcome.
 ...
PMID:Safety of a weekly high dose of liposomal amphotericin B for prophylaxis of invasive fungal infection in immunocompromised patients: PROPHYSOME Study. 1816 75


<< Previous 1 2 3 4 5 6 Next >>