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)

Short courses of cytosine arabinoside (Ara-C), cyclophosphamide, and L-asparaginase were given to seven children with newly diagnosed acute lymphocytic leukemia, who had failed to remit on standard remission induction therapy. These 4-day courses of Ara-C and cyclophophamide followed by 4 days of L-asparaginase were repeated at 3- to 4-week intervals for two or four courses. Complete remission occurred in six patients. The median duration of remission was 94+ days, on various maintenance regimens. The most serious side effect was neutropenia. This combination of these three drugs appears to be effective remission-induction therapy for children with ALL with unfavorable prognostic features.
Cancer 1975 Oct
PMID:Combination chemotherapy for children with acute lymphocytic leukemia who fail to respond to standard remission-induction therapy. 105 44

Amikacin, a new aminoglycoside antibiotic, was utilized in the treatment of 49 cases of infection which occurred in 39 neutropenic cancer patients. Thirty-four patients (69 per cent) responded to this antibiotic. Pneumonia and septicemia were the most common types of infection treated and the response rates were 65 per cent and 75 per cent, respectively. Gram-negative bacili were responsible for 93 per cent of the identified infections and 74 per cent responded. E. coli, Ps. aeruginosa, and organisms of the Klebsiella-Enterobacter-Serratia group were the most common gram-negative bacilli causing infection. Responses were more frequent among patients who maintained higher serum concentrations of antibiotic, but the differences were not statistically significant. Patients with severe neutropenia (less than 100 neutrophils/mm3) had a response rate of 68 per cent. Toxicity was manifested as azotemia and hearing loss which occurred in 13 per cent and 6 per cent, respectively. However, toxicity was directly related to serum concentration and to the number of treatments with amikacin. This antibiotic is of potential importance because of its efficacy against gram-negative bacilli infections. Best results were obtained when sufficient drug was given as a continuous intravenous infusion to maintain serum concentrations of about 15 mu g/ml.
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PMID:Amikacin therapy of infections in neutropenic patients. 110 49

As the first step in the study, the results of the NBT test in 83 patients with various untreated neoplasms, including 20 lymphomas, without bacterial infections and in 35 neoplastic patients with this complications were compared with the results obtained in control groups. No significant differences in the results were found between the groups of neoplastic patients without or with bacterial infections and the controls. To evaluate the NBT test during radio- and/or chemotherapy, especially in neutropenia, 45 patients were NBT-monitored. During the study of 102 episodes of neutropenia 43 infections occurred and 30 were NBT-confirmed. In remaining 13 cases it was impossible to perform the test because of extremely low neutrophil count (below 500/mul). All 20 infections in patients with normal neutrophil count were NBT-positive. These results confirm the usefulness of the test for infection screening in untreated with malignancies, as well as in patients receiving radio- and/or chemotherapy. However, the test can be taken only in patients without severe neutropenia.
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PMID:Value of the NBT test in the diagnosis of bacterial infection in untreated cancer patients and in those on radio- and/or chemotherapy. 122 95

Hematopoietic growth factors were found as factors stimulating hematopoietic colony formation in in vitro culture system using bone marrow cells as a source of hematopoietic progenitor cells. Erythropoietin, a growth factor stimulating erythroid lineage has now been clinically used as an therapeutic agent for anemia of chronic renal failure. Macrophage colony-stimulating factor (M-CSF), a growth factor stimulating the production of leukocytes including monocytes and neutrophils has been clinically used as an agent for leukopenic patients after anti-cancer therapy. M-CSF improves a survival rate after bone marrow transplantation (BMT) through the reduction of mortality rate associated with BMT such as bleeding, engraftment failure and GVHD. M-CSF accelerated platelet production when injected to thrombopenic patients with solid tumor after anticancer therapy. Granulocyte CSF (G-CSF) is a most powerful agent for various kinds of neutropenia such as neutropenia after anti cancer therapy, neutropenia after BMT, aplastic anemia, chronic neutropenia of children and myelodysplastic syndrome. However, since G-CSF stimulates growth of leukemic cells in vitro, careful observations should be required when clinically used on leukemic patients. Clinical studies of granulocyte-macrophage CSF (GM-CSF) and interleukin 3 (IL-3) are now in progress, in which a promoting activity of leukocyte production of these factors is evaluated.
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PMID:[Clinical application of hematopoietic growth factor (IL-3, G-CSF, GM-CSF, and EPO)]. 127 40

A total of 36 patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of 5-day continuous i.v. infusion of cisplatin (25 mg/m2 daily), bolus infusion of vindesine (3 mg/m2) on days 1 and 8, and s.c. injection of recombinant human granulocyte-colony-stimulating factor (2 micrograms/kg daily) on days 6-21. Treatment was repeated every 3-4 weeks. Responding patients with stage IIIA or IIIB disease received chest radiation therapy (50-60 Gy) after this treatment. One complete response and 23 partial responses were observed, for an overall response rate of 66.7% (24/36; 95% confidence limits, 51.3%-82.1%). The median duration of response was 5.7 months and the median overall survival was 10.1 months. WHO grade 3 or 4 leukopenia and neutropenia occurred in 22 (61%) and 27 (75%) patients, respectively, but the mean duration of leukopenia (< 2,000/mm3) and neutropenia (< 1,000/mm3) was 3.4 and 3.5 days, respectively, and there was no instance of life-threatening infection. Thrombocytopenia and anemia of grade 3 or 4 occurred in 28% and 36% of our subjects, respectively. Grade 2 nausea and vomiting occurred in 47% of the patients. Elevated serum creatinine levels (> 1.5 mg/dl) were observed in 3 (8%) of the 36 patients. One patient died of acute renal failure induced by hemorrhage of a gastric ulcer. This regimen is effective in the treatment of NSCLC and further studies of this combination are warranted.
Cancer Chemother Pharmacol 1992
PMID:Phase II study of cisplatin as a 5-day continuous infusion with vindesine plus recombinant human granulocyte-colony-stimulating factor in the treatment of advanced non-small-cell lung cancer. 128 May 37

We investigated the possibility of shortening the interval between courses of the commonly prescribed 28-day MVP (mitomycin C, vindesine, and cisplatin) regimen in patients with non-small-cell lung cancer (NSCLC). We conducted a nonrandomized phase II study using recombinant human granulocyte colony-stimulating factor (G-CSF, Chugai) to explore the possibility of shortening the cycle length to 21 days and compared the results with those obtained in historical controls who had received the standard 28-day regimen. A total of 40 patients, 37 of whom were evaluable, were entered in the 21-day treatment group of the trial and were compared with 38 historical controls who had received standard 28-day cycles of MVP at our institution. Patients in the 21-day group received mitomycin C at 8 mg/m2 on day 1, vindesine at 3 mg/m2 on days 1 and 8, and cisplatin at 80 mg/m2 on day 1, with the schedule being repeated every 21 days. Controls had received the same regimen, albeit at 28-day intervals. G-CSF was given s.c. to the patients in the 21-day group at a daily dose of 2 micrograms/kg from day 2 to day 21 of every MVP cycle. The administration of G-CSF to these patients accelerated neutrophil recovery as compared with that observed in the historical controls. Significant differences were found between the two groups in terms of mean neutrophil nadirs (2666/microliters in the first cycle and 1369/microliters in the second for the G-CSF group vs 416/microliters in the first cycle and 685/microliters in the second cycle for the control group; P < 0.0001) and the mean duration of neutropenia (< or = 1000/microliters; 1.0 day in the first cycle and 1.7 days in the second for the G-CSF group vs 8.0 days in the first cycle and 6.9 days in the second for the control group; P < 0.0001). This enabled 32 (86%) of 37 patients in the G-CSF group to complete > or = 2 cycles on schedule. In 10 patients, the bone marrow aspirates taken after G-CSF administration showed increases in band neutrophil and myelocyte percentages. In conclusion, MVP treatment of patients with NSCLC at 21-day intervals is possible with the support of G-CSF.
Cancer Chemother Pharmacol 1992
PMID:The use of granulocyte colony-stimulating factor to shorten the interval between cycles of mitomycin C, vindesine, and cisplatin chemotherapy in non-small-cell lung cancer. 128 46

During the 20-year period, 1972-1991, 27 episodes of Staphylococcus aureus bacteremia, including 10 with methicillin-resistant strains (MRSA), were documented in 26 patients with hematologic disorders, mainly acute leukemia and malignant lymphoma, representing 6% of all 433 episodes of bacteremia in a hematology unit. MRSA replaced methicillin-sensitive strains (MSSA) in the last four years. The skin and upper respiratory tract were the two most common primary foci. Most episodes occurred during neutropenia. Pharyngeal colonization often preceded the development of bacteremia. Antibiotic therapy predisposed to MRSA acquisition during hospitalization, whereas MSSA was mostly detected in admission cultures. Among 22 patients with monomicrobial bacteremia, 19 (86%) survived longer than one week, including all four with MRSA bacteremia who received vancomycin. The survival rate did not differ materially between MRSA and MSSA bacteremias. Secondary foci, chiefly located in the lung, were found in 30% of all patients with S. aureus bacteremia. Prolonged antibiotic therapy, therefore, seems warranted in patients with evident metastatic lesions, although abbreviated therapy is proposed in neutropenic cancer patients.
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PMID:Staphylococcus aureus bacteremia in patients with hematologic disorders. 129 23

The maximum serum levels of C-reactive protein (CRP) in 126 patients with hematological malignancies who had 554 febrile episodes were analyzed retrospectively with regard to documented infections and fever of unknown origin. The CRP levels were significantly higher when the blood culture was positive than when it was negative (p = 0.002). The CRP levels were significantly higher when the infection focus was identified than when it was not (p = 0.010). In patients with fever of unknown origin the CRP was significantly lower than in patients with microbiologically documented infections (p < 0.001). Cytotoxic treatment neither reduced nor enhanced the CRP reaction. The serial measurement of CRP is a reliable and readily available means for differentiating between bacterial infections and other causes of fever in patients with hematological malignancies, also during neutropenia and after cytotoxic treatment.
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PMID:Value of measurement of C-reactive protein in febrile patients with hematological malignancies. 129 65

Proliferation and differentiation of hematopoietic progenitor cells are regulated by a network of stimulatory and inhibitory cytokines. An understanding of the molecular mechanisms of growth control may provide a physiologic basis for the innovative therapy of bone marrow disorders. Among various accessory cells, bone marrow T lymphocytes are capable of stimulating, as well as inhibiting, hematopoietic progenitor cells. We have now elucidated molecular mechanisms regulating the differential expression of T cell genes encoding for the stimulatory and inhibitory hematopoietic programs. Stimulation of hematopoiesis requires granulocyte-macrophage colony stimulating factor (GM-CSF), whereas inhibition requires interferon-gamma (IF gamma). Both cytokines can be induced by interleukin-2 (IL2). The T cell IL2 receptor consists of a 75 kD chain (p75) mainly expressed on a subset of resting T cells and a 55 kD chain (p55) which is strongly expressed upon T cell activation. P55 and p75 associate on activated T cells to form a dimeric receptor molecule exhibiting high affinity for IL2. The p75 monomer has an intermediate affinity for IL2. Expression of p55 in the context of the high affinity IL2 receptor constitutes a requirement for T cell IFg release. In contrast, p75 alone is capable of mediating the production of GM-CSF. Thus, T cells may be capable of selective production of cytokines with specific effects in hematopoietic growth control. Utilizing a human peripheral blood leukocyte genomic library, we identified various clones containing the entire GM-CSF gene, including coding and regulatory regions. Cloning of the GM-CSF gene allowed clinical studies utilizing recombinant DNA-derived GM-CSF. Chemotherapy-induced neutropenia contributes to both complications of cytotoxic therapy as well as increased relapse incidence of underlying disease. In a prospective randomized study, we have demonstrated that GM-CSF abrogates neutropenia following aplasiogenic chemotherapy in children and adolescents with solid tumors, and that GM-CSF may reduce the duration of infectious episodes after cytotoxic therapy. Next, we escalated the cumulative doses of cytotoxic therapy in an ablative regimen followed by hematopoietic stem cell transplantation to treat patients with poor prognosis pediatric tumors. Morbidity of this highly toxic ablative regimen depends on the duration of myeloid aplasia. Median duration of aplasia following hyper-VAMP was 13 days with CM-CSF and 29 days without GM-CSF. In addition, we have employed p55 blocking monoclonal antibody for prevention of graft vs. host disease in bone marrow transplantation. The understanding of specific molecular mechanisms of hematopoietic immuno-regulation can thus be utilized to provide novel approaches to the treatment of bone marrow failure and cancer.
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PMID:Molecular regulation of hematopoietic cytokines: implications and indications for clinical use in pediatric oncology. 130 80

Etoposide is a schedule-dependent agent with greater activity against small cell lung cancer (SCLC) when a given dose is administered over several days compared with a 1-day administration of the same dose. In an attempt to capitalize on the schedule dependency of etoposide, 22 previously untreated extensive-stage SCLC patients were given cisplatin (100 mg/m2 on day 1) plus 21 days of low-dose, oral etoposide (50 mg/m2/d). Chemotherapy was repeated every 28 days for four cycles. Complete blood counts were monitored weekly, and etoposide was discontinued if either the leukocyte or platelet count dropped below 2000/microliters or 75,000/microliters, respectively. All 22 patients were evaluable for response; 18 had either a complete (9%) or partial response (73%), an overall response rate of 82% (95% confidence interval, 62% to 93%). The median response duration was 7 months, and the median survival was 9.9 months (range, 1 to 17+ months). Sixteen (73%) patients received all planned cycles of etoposide. In Cycle 1 of chemotherapy, the median leukocyte nadir was 2700/microliters (range, 100 to 6300/microliters), and median platelet nadir was 180,000/microliters (range, 51,000 to 397,000/microliters). Life-threatening leukopenia (less than 1000/microliters) was rare (3 of 74 cycles). There were three treatment-related deaths, only one of which was associated with neutropenia. One patient had mild renal insufficiency that resolved after discontinuation of therapy. Alopecia was observed in all patients, but other nonhematologic toxicities were uncommon. A randomized study is necessary to determine if this schedule of cisplatin and etoposide administration is superior to more standard methods. However, these data do not indicate a major survival benefit will be derived from increasing the duration of etoposide administration when used in combination with cisplatin given every 28 days.
Cancer 1992 Jan 15
PMID:A phase II trial of cisplatin and prolonged administration of oral etoposide in extensive-stage small cell lung cancer. 130 32


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