Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pattern of amphotericin B toxicity was assessed retrospectively in a group of 20 children with cancer who had received one or more courses of the drug for treatment of systemic fungal infection. Azotemia was the most frequent complication, developing during 23 of 24 treatment courses. Other major toxic effects, in decreasing order of frequency, were anemia, hypokalemia, thrombocytopenia, and neutropenia. Infusion side effects, including drug-related fever, chills, and nausea, were also frequently seen. Seventeen of 20 patients were treated for disseminated histoplasmosis. Nineteen of 20 patients had acute leukemia. Although interaction with other agents could not be excluded, amphotericin B appeared to be the major causative agent for the toxic reactions noted. In no patient, however, was administration of amphotericin B stopped because of drug toxicity.
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PMID:Toxicity of amphotericin b in children with cancer. 46 22

Twenty-three children with various stages and morphologic types of leukemia were treated with multiple granulocyte transfusions obtained by filtration leukapheresis when neutropenia-associated infection appeared unresponsive to antibiotics. All children meeting the above qualifications were given granulocyte transfusions during this time period. Twenty-one of 23 became afebrile during or shortly after the transfusions; one died with disseminated Herpes simplex; and one became well enough to be discharged, although he was never free of fever. Frequent mild to moderate fever and chills were noted. One child developed a severe pulmonary reaction followed by resolution of pneumonia. Filtration leukapheresis is a useful adjunct in controlling severe infections in neutropenic children.
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PMID:Granulocyte transfusions in children using filter-collected cells. 82 3

A new method called "repetitive filtration leukopheresis" is described for granulocyte transfusion therapy. 23 patients received a total of 91 transfusions. All patients presented neutropenia of less than 300/mm3 and various kinds of infection resistant to antibiotic therapy. A favorable result was observed in 18 cases following these transfusions, which did not produce the secondary effects noted by others (chills, rash, fever, dyspnea). It was felt that this remarkable tolerance was a result of the collection procedure (elution at pH 7.4 ommission of centrifugation, thus securing the functional integrity of the cells). This impression was confirmed by the results of a battery of tests performed on the collected granulocytes, which included evaluation of their phagocytic and bacteriolytic functions and of their ability to break down a phagocytized antigen, together with measurements of lysosomial enzymes released in the supernatant.
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PMID:[Granulocyte transfusions. Technical data, granulocyte function and results]. 100 57

The clinical use of amphotericin B is sometimes limited by nephrotoxicity. In a randomized prospective study, 32 patients treated for haematological malignancies received either amphotericin B in 5% dextrose (group A, 16 patients, 0.7-1 mg/kg/day), or amphotericin B mixed with Intralipid (group B, 16 patients, 0.7-1 mg/kg/day) during prolonged neutropenia. Renal dysfunction occurred in 9/16 patients in group A and 2/16 patients in group B (P < 0.05). Clinical tolerance was improved with a reduction of fever with chills in 12/16 patients in group A compared with 5/16 in group B (P < 0.05). Preparation of amphotericin B with Intralipid reduces nephrotoxicity, improves clinical tolerance, may allow an increase in the daily dose of amphotericin B, and be an alternative to liposomal-amphotericin B infusion.
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PMID:Reduced renal toxicity and improved clinical tolerance of amphotericin B mixed with intralipid compared with conventional amphotericin B in neutropenic patients. 838 21

Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-gamma (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 10(6) IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-gamma, 0.25 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-gamma, 0.1 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day.
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PMID:A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer. 151 22

This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studies with enzymes less than two times beyond the normal range. Twenty nine patients with gastric cancer and 26 with pancreatic cancer were entered from various institutions in the Southwest Oncology Group with 27 and 22, respectively, meeting eligibility criteria. Drug treatment consisted of rTNF (Genentech) given at a dose of 150 micrograms intravenously for five consecutive days every 3 weeks; 50% dose reduction was made for acute intolerance such as hypotension or severe fever and chills. Although eight patients with gastric cancer and five patients with pancreatic cancer received four or more courses of treatment, no objective antitumor responses were recorded. As in other trials common toxicities of rTNF included nausea and vomiting, chills and fever, hypotension, headache, myalgias, fatigue and malaise. However, in this trial, other toxicities became prominent: four episodes of symptomatic disseminated intravascular clotting occurred among patients with pancreatic cancer. Eleven with this disease and five with gastric cancer manifested laboratory findings of abnormal amounts of fibrin split products, and/or hypofibrinogenemia, and/or thrombocytopenia after treatment began. Other laboratory abnormalities that were commonly encountered included hyperglycemia, hypertriglyceridemia, anemia, neutropenia and an elevation in liver enzymes. We conclude that rTNF does not demonstrate antitumor efficacy against adenocarcinomas of the stomach and the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers. 152

Ten patients with advanced urologic cancers who were scheduled to receive at least two courses of chemotherapy were enrolled in this trial. Fifty thousand units of recombinant human interleukin-1 (IL-1) beta analogue OCT-43 (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) was administered subcutaneously only once or twice when severe neutropenia (less than 500/microliters) continued for 2 consecutive days. In eight patients, OCT-43 was not injected in the first course of chemotherapy as a control, but was injected in the second course. The durations of leukocytopenia (less than 2000/microliters) and neutropenia (less than 1000/microliters) were significantly shortened in the second course compared with those in the first course in those eight patients. Recovery of neutrophil number from the lowest number was also significantly faster in the second course. Thus, OCT-43 was considered to have hematopoietic activities. However, single or double injection of OCT-43 did not affect the numbers of eosinophilic or basophilic granulocytes, monocytes, or platelets. Adverse effects associated with OCT-43 injections were high fever and chills, but they were controlled by indomethacin.
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PMID:Recombinant human interleukin-1 beta analogue as a regulator of hematopoiesis in patients receiving chemotherapy for urogenital cancers. 189 51

The purpose of the study was to evaluate the toxicity and biological activity of highly purified lipopolysaccharide (LPS) administered intravenously to cancer patients in order to establish an optimum dosage scheme. An initial subtoxic dose was increased in weekly increments in accordance with individual regimens that maintained patient reaction at a safe and acceptable level. Purified LPS from Salmonella abortus equi was administered to 11 patients with advanced solid tumors on a weekly schedule with intraindividually escalating dosage as determined by patient response. Biological response was monitored by complete blood count, C-reactive protein, and cytokine measurements at different time points after LPS injection. Tumor necrosis factor-alpha (TNF) and interleukin-1 beta serum levels were measured by enzyme-linked immunosorbent assay and interleukin-6 (IL-6) by bioassay. Dose-limiting toxicities including chills and fever (WHO grade III) were reached at 1.0 ng/kg of body weight (maximal tolerated dose-1, MTD-1). Pretreatment with ibuprofen (1,600 mg) abrogated these side effects, allowing further escalation of LPS doses up to 10 ng/kg of body weight. At dose levels greater than 8.0 ng/kg of body weight (MTD-2), the aforementioned side effects occurred again and, additionally, hepatic toxicity (WHO grade III) was observed. Hematological changes included neutropenia followed by a pronounced neutrophilia contributed to by up to 30% bands, marked monocytopenia for 3 h, and retarded lymphopenia. By 24 h, all hematological parameters returned to pretreatment values. TNF serum levels increased from 10 pg/ml before treatment to 7,000 pg/ml as a function of dosage. Maximum serum levels were reached at 60 to 90 min after LPS injection. Similarly, IL-6 serum concentrations increased from less than 4 to 2,500 U/ml; peak levels were obtained 30 min after TNF peak values. Prior administration of ibuprofen had no effect on the above-mentioned hematological changes nor on cytokine release. LPS can be administered intravenously in weekly intervals at escalating doses from 0.15-10.0 ng/kg of body weight, when patients are protected by pretreatment with ibuprofen at dose levels above 1.0 ng/kg of body weight. Cytokine release as measured by TNF and IL-6 increased in a dose-dependent manner although the constitutional symptoms are completely attenuated.
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PMID:Biological response to intravenously administered endotoxin in patients with advanced cancer. 225 60

A seven year old boy with a history of cyclic neutropenia (CN) was admitted to the hospital after developing fever and chills following a bicycle accident. After admission, he had a rapidly deteriorating hospital course leading to shock and death. At autopsy, acute appendicitis with resultant peritonitis and sepsis was diagnosed. The peculiar clinical and microscopic aspects of this case will be presented and contrasted with the more usual signs and symptoms of this cyclic disease.
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PMID:Cyclic neutropenia: a case of asymptomatic appendicitis. 260 79

Because recombinant interleukin 2 (rIL-2) and recombinant alpha-interferon (rIFN-alpha) exhibit synergistic antitumor activity in C3HMT1820 T-cell lymphoma and B16 melanoma tumor systems, we have performed a Phase I study of this combination in 55 patients with advanced malignancies for whom no standard therapy exists. Successive groups of greater than or equal to 4 patients have been entered into 12 dose levels (1A-3D), with dose levels 1-3 referring to doses of rIL-2 of 0.1, 0.5, and 2.0 x 10(6) units/m2, respectively, and dose levels A-D referring to doses of recombinant human alpha 2a-interferon (rHuIFN-alpha 2a) of 0, 0.1, 1.0, and 10.0 x 10(6) units/m2. Both agents were given on Mondays, Wednesdays, and Fridays, with rIL-2 being given as i.v. bolus injections and rHuIFN-alpha 2a being given intramuscularly. Myelosuppression was dose-limiting and was related primarily to the dose of rHuIFN-alpha 2a. The maximum-tolerated dose level was reached at a dose of rIL-2 of 2.0 x 10(6) units/m2 and of rHuIFN-alpha 2a of 10.0 x 10(6) units/m2 (dose level 3D). At this dose level, 3/6 patients developed grade 3 neutropenia (absolute granulocyte count less than 1 x 10(9)/liter). Myelosuppression was transient, with no documented infections being associated with neutropenia. Hypotension was mild; a single patient was treated with a vasopressor, but all other cases of hypotension responded to fluid administration. No significant pulmonary toxicity was produced. Fever, chills, and malaise were universal but not dose-limiting. Three partial responses and one minor response were observed in patients with malignant melanoma, renal cell carcinoma, and breast cancer. Immunological studies suggested that natural killer activity was related to both the dose of rIL-2 and the dose of rHuIFN-alpha 2a, with natural killer activity being positively related to the dose of rIL-2 and maximal at the lowest dose of rHuIFN-alpha 2a of 0.1 x 10(6) units/m2.
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PMID:Phase I clinical trial of interleukin 2 and alpha-interferon: toxicity and immunologic effects. 280 86


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