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)

In an effort to search for new, synergistic and non-cross-resistant antileukemic regimens, the Cancer and Leukemia Group B (CALGB) investigated the activity and toxicity of mitoxantrone in combination with etoposide for the reinduction of patients with relapsed or refractory acute myelocytic leukemia (AML). Mitoxantrone, 12 mg/m2 daily for 3 days, was combined with three dose levels of etoposide, 100, 150 and 200 mg/m2 daily by constant infusion for 5 days. There were 19 male and 13 female patients, with a median age of 46 (range, 21-74). Of these, nine were primarily refractory to daunorubicin and ara-C; 17 had one prior complete remission (CR), five had two prior CR, and one had three prior CR. Thirteen patients were entered at the first dose level, 11 were entered at the second, and eight at the third. All but one patient, whose death occurred within the first 2 days of treatment, are evaluable for toxicity. There were five CR (four at the first and one at the second dose level) and six partial remissions (PR) (three at the first dose level and three at the second). Unmaintained responses lasted 6-33 weeks. Median survival for all patients was 12.6 weeks. Anti-leukemic effects with severe marrow hypoplasia were observed in all patients; severe nausea and vomiting were seen in four. Severe mucositis, often indistinguishable from superimposed candidiasis, occurred in 40% of all patients; it was associated with dose-limiting esophagitis (three of seven evaluable patients) at the highest etoposide dose. Hepatic and renal dysfunction was severe in three patients; no treatment-related severe pulmonary or cardiac toxicity was observed. Posttreatment infectious complications were severe in 11 patients. In three cases, they were fatal--an incidence not dissimilar from that of other reinduction regimens in heavily pretreated patients. The regimen appears to be active; the combination of mitoxantrone, 12 mg/m2 daily for 3 days, with etoposide, 150 mg/m2/day for 5 days, by constant intravenous infusion is now being explored by the CALGB in a randomized phase II study against mitoxantrone plus diazoquinone and diazoquinone plus etoposide.
 ...
PMID:Mitoxantrone and constant infusion etoposide for relapsed and refractory acute myelocytic leukemia. 223 6

Deep mycoses present new aspects characterized by deep, visceral mycotic localisations and septicemia, particularly in immunocompromised conditions. In immunodepressed patients (leukaemia, transplantation), the granulopenia descending to 500 elements/ml leads not only to invasive aspergillosis and candidosis but also to infections due to opportunistic fungi exceptionally or never seen formerly. AIDS favours opportunistic fungi related to defective cellular immunity as Cryptococcus neoformans, responsible of severe meningoencephalitis and septicemia, as Candida albicans responsible of thrush and oesophagitis, but also true pathogenic fungi (Histoplasma capsulatum) becoming opportunistic in such conditions. C. albicans provokes in heroin addicts a new septicemic syndrome with cutaneous, ocular and osteoarticular lesions and in leukaemic patients hepatic micro-abscesses soon after the neutropenic phase induced by chemotherapy. New methods for immunologic diagnosis (research of circulating fungal antigen), for clinical diagnosis (scanning, magnetic resonance). New strategy of antifungal chemotherapy (itraconazole, fluconazole) allow to a better knowledge and control of this new infectious pathology.
 ...
PMID:[Current role of deep mycoses in infectious pathology]. 281 46

Infections of the esophagus are common in individuals with altered immune status. A review of the literature reveals that, in such patients, fungal organisms, particularly Candida and Aspergillus, can invade deeply into esophageal muscle. We report the development of a tracheoesophageal fistula following polymicrobial infectious esophagitis. This case, of a young woman with leukemia, emphasizes the need for early recognition and aggressive treatment of esophageal infections.
 ...
PMID:Tracheoesophageal fistula: a serious complication of infectious esophagitis. 659 23

Thirteen patients with relapsed acute leukemia, 12 adults with acute nonlymphocytic leukemia, and one child with acute lymphoblastic leukemia were treated with VP 16-213, an epipodophyllotoxin analog, at a dose of 200-300 mg/m2/day X5 as a 2-hour intravenous infusion. Only four patients achieved bone marrow aplasia and three regenerated with leukemic cells. The fourth patient achieved a partial remission for 4 weeks. Toxicities included myelosuppression (WBC nadir 500/microliter), nausea and vomiting (70% of courses), mucositis (23%), esophagitis (12%), which contributed to death in one patient, hypotension (12%), and transient liver function abnormalities (12%). It is concluded that increasing the dose of VP 16-213 as employed in this study did not increase the therapeutic activity of VP 16-213 for the treatment of relapsed leukemia but did increase the risk of toxicity.
 ...
PMID:High-dose VP 16-213 (NSC 141540) for the treatment of patients with previously treated acute leukemia. 693 27

Invasive fungal infection is an increasing problem in severely immunocompromised patients. A 30-year-old man with profound pancytopenia due to acute myelogenous leukaemia acquired a severe invasive candida oesophagitis with total desquamation and expulsion of 90 mm of the distal oesophagus. The case report lends support to the concept of early recognition of fungal oesophagitis including species identification and possibly also antimycotic prophylaxis during immunosuppressive treatment.
 ...
PMID:Nonfatal total expulsion of the distal oesophagus due to invasive candida oesophagitis. 846 Mar 42

The high-dose sequential regimen developed by Gianni et al. in Milan is a novel concept in which five active drugs are administered sequentially at their maximum tolerated dosages. In previous studies this treatment was efficacious in relapsed Hodgkin's disease and in "de novo" high-risk high-grade NHL. We tested the feasibility, toxicity and efficacy of this approach, administered with simplified supportive measures, as salvage regimen for patients with relapsed (n = 17) or resistant (n = 3) lymphoma (9 high-grade NHL, 4 low-grade NHL and 7 Hodgkin's disease). The regimen included sequential administration of cyclophosphamide (7 g/m2), methotrexate (8 g/m2), etoposide (2 g/m2), mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) over a period of 8 weeks in an effort to reduce hospitalisation to a minimum. Of the 20 initial patients, 15 completed the planned programme. The regimen was subjectively well tolerated despite frequent hospital stays (median 44 days). Recovery of absolute neutrophil and platelet counts after transplantation occurred on the average on days 13 and 11 respectively. A second neutrophil and platelet nadir was seen 7-8 weeks after transplantation. Long-term side effects were a severe stenosing postactinic oesophagitis and a secondary subacute monoblastic leukaemia. At a median follow-up of 24 months, the 2 years disease-free and overall survival are 27% and 60% respectively. Of the 15 patients actually transplanted, 7 (47%) are alive disease-free. Although as feasible and effective as other high-dose regimens, this regimen requires longer hospital stays and its costs may be higher than those of other high-dose programmes.
 ...
PMID:High-dose sequential chemotherapy with autologous blood stem cell rescue for relapsed or resistant lymphoma. 988 64

A randomized phase II trial conducted by the Cancer and Leukemia Group B in patients with unresectable non-small cell lung cancer showed that induction chemotherapy followed by concurrent radiotherapy and chemotherapy was feasible when cisplatin was administered together with either gemcitabine, vinorelbine, or paclitaxel. The dominant toxicity was esophagitis. Preliminary survival data are encouraging. Other trials in progress or planned will elucidate the relative contributions of induction and concurrent therapy to outcome. A phase I study has shown that it is feasible to combine docetaxel (Taxotere: Aventis, Antony, France) with concomitant radiotherapy in patients with advanced non-small cell lung or esophageal cancer. Giving the drug once every 3 weeks during standard radiotherapy, the maximum tolerated dose is 40 mg/m2 per cycle. The dose-limiting toxicities are neutropenia and esophagitis. However, it is possible to escalate the total docetaxel dose to 60 mg/m2 per cycle by weekly administration of 20 mg/m2. Beyond this point, esophagitis is dose limiting. In the palliative-intent treatment setting, the weekly administration of docetaxel is also likely to be a helpful new approach to administering the drug in subgroups of patients such as the elderly and those with concomitant disease. Weekly docetaxel (36 mg/m2/wk) was administered to patients with advanced non-small cell lung cancer who were elderly (median age, 71 years) or had poor performance status. In this unfavorable group, weekly docetaxel produced a 19% objective response rate and with further follow-up, 1-year survival is 28%. This level of activity is similar to other single agents recently evaluated in more favorable patient groups. The lack of myelosuppression seen with weekly administration suggests that the dose intensity of docetaxel could be maintained in combination regimens.
 ...
PMID:Docetaxel (Taxotere) in combination with radiation therapy and the potential of weekly administration in elderly and/or poor performance status patients with advanced non-small cell lung cancer. 1128 21

In order to investigate the underlying mechanism of HCl in oesophagitis, the inflammatory response to HCl was observed in RBL-2H3 mast cells. Rat basophilic leukemia (RBL-2H3) cells were used to measure histamine release, arachidonic acid (AA) release, reactive oxygen species (ROS) and peroxynitrite generation induced by HCl. Exogenous HCl increased the level of histamine release and ROS generation in a dose dependent manner, whereas it decreased the spontaneous release of [3H] AA and the spontaneous production of peroxynitrite. Mepacrine (10 microM), oleyloxyethyl phosphorylcholine (10 microM) and bromoenol lactone (10 microM) did not affect both the level of histamine release and ROS generation induced by HCl. U73122 (1 microM), a specific phospholipase C (PLC) inhibitor did not have any influence on level of histamine release and ROS generation. Propranolol (200 microM), a phospholipase D (PLD) inhibitor, and neomycin (1 mM), a nonspecific PLC and PLD inhibitor, significantly inhibited both histamine release and ROS generation. Diphenyleneiodonium (10 microM), a NADPH oxidase inhibitor, and tiron (5 mM), an intracellular ROS scavenger significantly inhibited the HCl-induced histamine release and ROS generation. These findings suggest that the inflammatory responses to HCl is related to histamine release and ROS generation, and that the ROS generation by HCl may be involved in histamine release via the PLD pathway in RBL-2H3 cells.
 ...
PMID:Histamine release by hydrochloric acid is mediated via reactive oxygen species generation and phospholipase D in RBL-2H3 mast cells. 1243 4

Infectious esophagitis can have significant implications in an impaired host. Described most commonly in immunocompromised patients, infectious esophagitis can also occasionally be discovered in immunocompetent individuals in several unique clinical settings. Evaluation of the typical presenting complaints, such as dysphagia or odynophagia, are especially important in immunocompetent patients, and therapy should be directed at the appropriate predisposing condition and resultant infectious agent. In immunocompromised patients, however, clinical experience supports the use of empiric therapy in patients without concomitant systemic complaints. Especially in AIDS patients or those with lymphoma or leukemia, the initial approach to infectious esophagitis complaints (ie, dysphagia or odynophagia) is to begin an empiric trial of oral systemic fluconazole for presumed candidal esophagitis. If the individual remains symptomatic after 3 to 7 days or has any associated systemic complaints or concerning clinical findings (eg, hematemesis), then upper endoscopy with biopsies is indicated. If an etiologic agent other than Candida is defined by histologic, immunohistochemical, or culture methods, then appropriate therapy can be initiated. There are many important and pathologic agents implicated in infectious esophagitis. Thus, directed therapy needs to be administered appropriately and in a timely fashion to avoid poor short-term problems or long-term sequelae.
 ...
PMID:Infectious Esophagitis. 1252 73

Lung cancer remains the leading cause of cancer-related mortality in the United States and 30% to 40% of newly diagnosed patients with non-small cell lung cancer present with regionally advanced and unresectable stage III disease. Combined-modality therapy is the current standard of care in patients with good performance status at the time of diagnosis and recent trials have suggested a survival advantage for the concurrent use of chemotherapy and thoracic radiation therapy at the risk of increased toxicity (mainly esophagitis and myelosuppression). The Cancer and Leukemia Group B has been instrumental in shaping the standard of care in the combined-modality approach to unresectable stage III non-small cell lung cancer. Currently, Cancer and Leukemia Group B is conducting trials evaluating novel thoracic radiation therapy strategies as well as the incorporation of molecularly targeted agents, yielding encouraging preliminary data. In addition, a change in the therapeutic platform is planned that explores a full-dose systemic approach with the antifolate pemetrexed that possesses radiosensitizing properties.
 ...
PMID:Combined modality trials in unresectable stage III non-small cell lung cancer: the Cancer and Leukemia Group B experience. 1601 47


1 2 Next >>