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)

COP-BLAM III therapy was given to 18 patients with non-Hodgkin's lymphoma, and the therapeutic effects as well as adverse effects of the treatment were examined. Of the 18 patients 16 had a complete remission (CR) and 2 showed an partial remission (PR) with a total response rate of 100%. In terms of the stage of disease, CR was achieved in all patients in stage III and in 11 of 13 patients in stage IV. Patients with neutrophil counts less than 1,000/microliters were given rhG-CSF (1.5 micrograms/kg/day, sc), which significantly shortened the duration of neutropenia and decreased the number of days with episodes of fever when compared with those not given rhG-CSF, consequently facilitating the treatment without prolonging the dosing intervals. No serious infection was observed. Adverse effects included neutropenia of less than 1,000/microliters in 6 of the 18 patients (33.3%), thrombocytopenia less than 5 x 10(4)/microliters in 3 (16.7%), nausea and vomiting in 8 (44.4%), peripheral neuropathy in 4 (22.2%) and stomatitis in 4 (22.2%). There were no fatalities caused by the treatment. The above findings indicate that COP-BLAM III therapy is capable inducing high frequency of complete remissions in non-Hodgkin's lymphoma and that its combination with G-CSF can improve the results of the therapy and relieve adverse reactions.
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PMID:[The COP-BLAM III therapy of non-Hodgkin's lymphoma]. 172 37

A 63-year-old Japanese woman who was being treated for liver cirrhosis was diagnosed as having hepatocellular carcinoma in the caudate lobe of the liver. Transcatheter hepatic arterial chemoembolization was performed for this lesion, but severe neutropenia occurred. To restore white blood cell (WBC) counts, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (250 micrograms per day during 10 days, intravenously). Subsequently, WBC counts recovered immediately without side effects. This suggests that rhG-CSF could be useful for the treatment of neutropenia after chemoembolization, even in cirrhotic patients.
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PMID:An application of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a case of hepatocellular carcinoma combined with liver cirrhosis in which leukopenia developed after chemoembolization. 172 72

The therapeutic and hematological effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in combination with cyclophosphamide (CY) were investigated in a murine myeloid leukemia model. Ten daily administrations of rhG-CSF following CY prolonged the survival time of leukemic mice more than either agent alone. Hematological examination indicated that this effect was attributable to suppression with rhG-CSF of the leukemic repopulation after CY injection. In addition, rhG-CSF accelerated recovery from CY-induced neutropenia. Based on these hematological changes, a treatment regimen was established consisting of a single injection of CY on day 1 and daily injections of rhG-CSF on days 2-6; this combination treatment was given to the leukemic mice for up to four cycles, with a pause of one day between each cycle. The leukemic mice completed each cycle of treatment with few failures, and it resulted in a long survival time for the leukemic mice. The mean survival time of the mice receiving four cycles of treatment was 47 days, 30 days longer than that of the untreated mice. Hematological examination performed at the end of each cycle showed that the leukemic cell population was controlled at a level equal to or below the pre-treatment level, and peripheral blood neutrophils were maintained at a level equal to or above the normal level. These results indicate the possible effectiveness of combining rhG-CSF with chemotherapeutic drugs in controlling leukemic cell growth, and the effectiveness of rhG-CSF in enhancing neutrophil recovery after chemotherapy. However, it was found that the leukemic cells became resistant to treatment with rhG-CSF after four cycles of combination treatment, suggesting that great care should be taken in the clinical application of rhG-CSF, even when the growth of acute myelogenous leukemia cells is not apparently stimulated by it.
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PMID:Long survival of leukemic mice by repeated combination treatment of cyclophosphamide and recombinant human granulocyte colony-stimulating factor. 172 31

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was investigated for its clinical efficacy in the treatment of various types of neutropenia (3 cases with idiopathic neutropenia of suspected drug induction, 5 cases with idiopathic neutropenia of other origin, and 2 cases with cyclic neutropenia). Treatment with glycosylated rhG-CSF produced in the Chinese Hamster Ovary cells at dose levels of 2-5 micrograms/kg/day caused rapid increases of neutrophil counts associated with an improvement of the infection. In cyclic neutropenia patients, marked reduction in the duration of the neutropenic period was observed with rhG-CSF administration started before the period. Intercurrent stomatitis, which occurred in 1 patient, was markedly milder as compared to a previous episode which occurred during an untreated neutropenic period. The treatment of rhG-CSF was well tolerated and no adverse events were observed, nor was there any detectable anti-rhG-CSF antibody in any patients studied; hence the clinical use of rhG-CSF is considered to be safe. These results suggest beneficial effects of rhG-CSF on the recovery of neutrophil counts in cyclic and other types of idiopathic neutropenias, as well as for the treatment of neutropenia-associated infection.
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PMID:Clinical effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on various types of neutropenia including cyclic neutropenia. 172 91

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now undergoing clinical trials. We investigated the effects of rhG-CSF on the function of neutrophils in vivo in healthy volunteers. rhG-CSF (0.5 micrograms/kg) was injected subcutaneously for 6 consecutive days. The number of neutrophils in peripheral blood decreased transiently within an hour, and thereafter increased 2-10-fold compared to the control 6 to 8 h after injection. The circulating neutrophils remaining during this early neutropenic period showed increases in such functions as random motility, chemotaxis, phagocytosis and superoxide anion production. On the other hand, the function of neutrophils which increased 6 to 8 h after rhG-CSF injection was normal. No decrease of neutrophil function was observed following the use of rhG-CSF. CD33-positive cells increased 3 days after rhG-CSF administration. CD11a (LFA-1) expression on the membranes circulating neutrophils decreased 6 h after rhG-CSF administration. This phenomenon suggested that neutrophils adhered to the reticuloendothelial system during neutropenia, and that there was an influx of CD11a-negative mature cells into the circulatory pool thereafter. All our findings suggest that rhG-CSF enhances the function of normal neutrophils in vivo, and that it is effective against microbial infection very soon after administration.
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PMID:In vivo effects of recombinant human granulocyte colony-stimulating factor on normal neutrophil function and membrane effector molecule expression. 172 90

During states of increased demand, neonatal host defense is characterized by dysregulation of granulopoiesis, resulting in a high incidence of neutropenia. This study investigated the modulation of neonatal rat hematopoiesis by 14-d administration of recombinant human (rh) IL-6, rh-granulocyte-colony stimulating factor (G-CSF), or sequential combination of rhIL-6 and rhG-CSF. Specifically, newborn Sprague-Dawley rats were treated with either rhIL-6 (5 micrograms/kg/d for 14 d), rhG-CSF (5 micrograms/kg/d for 14 d), rhIL-6 for 7 d followed by rhG-CSF for 7 d, PBS/BSA for 7 d followed by rhG-CSF for 7 d, or PBS/BSA for 14 d. RhIL-6 alone significantly increased the peripheral platelet count during the latter part of the 2nd wk of administration (d 13: 980 +/- 42 versus 716 +/- 23 x 10(3)/mm3) (p = less than 0.001) (mean +/- SEM). Treatment with rhIL-6 for 7 d followed by rhG-CSF significantly increased the peripheral neutrophil count compared with 7 d of PBS/BSA and 7 d of G-CSF (d 14 absolute neutrophil count 4888 +/- 12 versus 2720 +/- 317/mm3) (p = less than 0.05). Similarly, sequential rhIL-6/rhG-CSF significantly increased the d-14 bone marrow neutrophil storage pool (9873 +/- 882 versus 3564 +/- 159/mm3) (p = less than 0.005). Lastly, sequential rhIL-6/rhG-CSF induced the highest increase in bone marrow (p less than 0.01) and liver/spleen CFU-GM pool (p less than 0.001) compared with any other treatment group. These studies suggest that rhIL-6 alone is associated with a significant increase in the neonatal platelet count.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sequential administration of interleukin-6 and granulocyte-colony stimulating factor in newborn rats: modulation of newborn granulopoiesis and thrombopoiesis. 172 8

Recombinant granulocyte colony-stimulating factor (rG-CSF) primed the ability of human neutrophils to generate increased levels of reactive oxidants in response to fMet-Leu-Phe, and also resulted in an increased rate of protein biosynthesis which was similar to that induced by granulocyte-macrophage colony-stimulating factor. However, rG-CSF reduced the chemotactic activity of neutrophils in response to endotoxin and did not result in an enhanced rate of killing of Staphylococcus aureus. rG-CSF was administered to patients after high dose chemotherapy and autologous bone marrow transplantation for the treatment of either Hodgkin's disease or multiple myeloma. This cytokine decreased the period of neutropenia following such treatment. Neutrophil function in two patients, measured seven days after the final administration of rG-CSF, was severely impaired as indicated by a greatly decreased ability to generate reactive oxidants. However, seven days later (i.e. 14 days post-therapy), the functional activity of the neutrophils from these patients had returned to normal. These data indicate that assays of neutrophil function together with morphological assessment of neutrophil numbers and maturity should be performed in order to evaluate the immune status of patients undergoing such therapy.
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PMID:Effects of recombinant human granulocyte colony-stimulating factor on neutrophil function in vitro and in vivo following chemotherapy and autologous bone marrow transplantation. 172 83

We describe the case of a 12-year-old boy affected by cyclic neutropenia, at high risk of developing life-threatening infections, treated with recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF). The drug was effective in reducing the severity of neutropenia and infectious complications in our patient. It was administered for brief periods of time, in contrast to the daily continuous administration reported for rHuG-CSF. Therefore, more extensive studies must be performed to identify the most effective time schedule for the drug. In vitro studies of hemopoietic progenitor cells were useful, in this case, to predict treatment response.
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PMID:Recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF) in cyclic neutropenia. 174 95

The human recombinant GM-CSF (hrGM-CSF) is a glycosylated hematopoietic growth factor, derived from CHO cells (Schering Plough/Sandoz) used in these studies. The hrGM-CSF can be given intravenously (i.v.) in 4- to 24-h infusions or subcutaneously (scx) once or twice a day. Many patients (more than a thousand) have been treated with the hrGM-CSF in various pathologies, in association with anti-cancer chemotherapy, after bone marrow transplants or for myelodysplasias, refractory anemias, some neutropenias and infections. The reversion of neutropenia is dose-dependent with either a sc or i.v. administration. Recommended doses are from 5.0 to 10.0 micrograms/kg/per day. When the product is given sc the effect is delayed by one day but is more prolonged than with the i.v. route. The treatment duration has been investigated in different studies: a minimal duration of 5 days seems appropriate. When given in association with high doses of cytotoxic chemotherapeutic agents 10 to 14 days are required. In bone marrow transplants (autologous or allogenic with T-cell depletion), the hrGM-CSF has been shown to significantly reduce the time necessary for engraftment. Contrary to some fears, it was not shown that hrGM-CSF increased the risk of blastic transformation in myelodysplastic syndromes. In association with cytosine-arabinoside a certain number of partial and complete responses have been obtained. The toxic effects of the product are also dose-dependent. At doses greater than 11 micrograms/kg per day, there is a risk of stimulating inflammatory phenomena whereas at lower doses, more moderate side effects (myalgia, fever, injection site reaction) occur in only 30% of the cases. The GM-CSF will certainly be important in the future in haematology, oncology and for the treatment of infectious diseases.
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PMID:Recombinant human GM-CSF: present clinical results and potential use in oncologic and hematologic disorders. 178 28

Doxorubicin and ifosfamide are the two most active agents used in the treatment of advanced inoperable soft-tissue sarcoma, but their use in combination produces dose-limiting myelosuppression. To explore the feasibility of combining optimal doses of both drugs, doxorubicin (75 mg/m2) and ifosfamide (5 g/m2) were given every 3 weeks with recombinant human granulocyte/macrophage-colony-stimulating factor (rhGM-CSF; 250 micrograms m-2 day-1) by subcutaneous injection for up to 14 days after each course. A total of 52 patients with progressive metastatic soft-tissue sarcoma were entered, none having received prior chemotherapy. One patient was ineligible and received no treatment after registration. Preliminary analysis of six cycles of chemotherapy revealed that the full protocol dose intensity had been administered to the majority of patients. Although the median leucocyte and neutrophil counts did not fall with subsequent courses of chemotherapy, the duration of neutropenia increased with each course delivered. Cumulative thrombocytopenia was a major dose-limiting toxicity and was the main reason for any dose modifications that occurred. Although 26 patients experienced infections after one or more courses of treatment, in only 7 was admission required for parenteral antibiotics. One patient died as a result of septicaemia after the first cycle of treatment. To date, there have been 22 responses (43%) with 8% complete remissions. It appears that the administration of rhGM-CSF allows this high-dose regime of chemotherapy to be given safely and the early encouraging response rate adds support to the concept that increasing the dose of doxorubicin improves the outlook for patients with advanced soft-tissue sarcomas.
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PMID:Doxorubicin plus ifosfamide with rhGM-CSF in the treatment of advanced adult soft-tissue sarcomas: preliminary results of a phase II study from the EORTC Soft-Tissue and Bone Sarcoma Group. 179 8


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