Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151825 (bone pain)
 3,118 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Filgrastim (granulocyte colony stimulating factor) recently became commercially available for the treatment of chemotherapy-induced neutropenia. Studies have shown that filgrastim induces a dose-dependent granulocytosis in humans, thereby shortening the period of neutropenia in patients treated conventionally with submarrow ablative doses of chemotherapy, as well as with marrow ablative therapy given in the bone marrow transplant setting. By reducing the incidence and severity of infections and mucositis in patients treated with chemotherapy, it has a significant economic impact since it shortens the duration of antibiotic administration and hospitalization. Adverse reactions reported are limited to mild to moderate bone pain. Several other potential applications are being investigated for filgrastim, including treatment of patients with myelodysplastic syndrome and congenital neutropenia.
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PMID:Topics in clinical pharmacology: filgrastim, a myeloid colony stimulating factor. 137 51

Filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF), has identical biological activity to that of endogenous human G-CSF, but differs in that it contains an N-terminal methionine residue and is not glycosylated. It principally stimulates activation, proliferation and differentiation of neutrophil progenitor cells and has been evaluated in the treatment of patients with various neutropenic conditions, both iatrogenic and disease-related. Two comparative studies have demonstrated that prophylactic administration of filgrastim 230 micrograms/m2/day significantly reduces the incidence, duration and severity of neutropenia in patients with previously untreated small-cell lung cancer receiving standard-dose chemotherapy with CDE (cyclophosphamide, doxorubicin plus etoposide). Concomitant with the amelioration of neutropenia, the incidence of febrile neutropenia was significantly reduced by 50% and there were 35 and 50% decreases in hospitalisation rates and intravenous antibiotic requirements. Since not all patients receiving standard-dose chemotherapy are at risk of infectious complications, prophylactic filgrastim use may be reserved for those patients who have developed febrile neutropenia during a previous cycle of the same regimen. This strategy may prove less costly, although potential savings must be weighed against a greater risk of patient morbidity and reduced quality of life. When combined with standard intravenous antibiotic therapy, filgrastim further decreases morbidity in patients with established febrile neutropenia and may have a positive impact on overall treatment costs by shortening the length of hospitalisation. Attention is focused on the use of haematopoietic growth factors to support dose-intensification of chemotherapy with a view to improving treatment outcomes in patients with chemo-responsive tumours. Filgrastim, used alone, permits modest increases in dose-intensity and/or dose-escalation of some standard-dose chemotherapy regimens. Moreover, the drug has proven useful as an adjunct to myeloablative chemotherapy followed by stem cell rescue with autologous bone marrow transplantation and/or peripheral blood progenitor cells. However, the impact of these dose-intensification approaches on survival remains to be determined in well-controlled clinical studies. Filgrastim is effective in increasing the neutrophil count and decreasing morbidity in patients with severe chronic neutropenia, including Kostmann's syndrome, and in idiopathic and cyclic neutropenia. In addition, filgrastim has accelerated neutrophil recovery in patients with idiosyncratic drug-induced agranulocytosis. Available data indicate that filgrastim is generally well tolerated. The most frequent adverse reaction is mild to moderate medullary bone pain, reported by approximately 20% of patients, although this can generally be controlled using simple analgesics without the need to discontinue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Filgrastim. A review of its pharmacological properties and therapeutic efficacy in neutropenia. 753 Jun 30

Lenograstim is a recombinant glycosylated human granulocyte colony-stimulating factor (rHuG-CSF) which principally regulates the formation and function of neutrophils. Like other colony-stimulating factors (CSFs), lenograstim has been developed for the prevention and treatment of iatrogenic and disease-related neutropenic conditions. In phase III clinical studies, prophylactic administration of lenograstim shortened the duration of chemotherapy-induced neutropenia in patients with nonmyelogenous cancers who received standard-dose chemotherapy or myeloablative regimens followed by bone marrow transplantation (BMT). A decrease in the incidence of infection after standard regimens and fewer days with infectious and febrile neutropenic episodes during recovery from BMT occurred concomitantly with the amelioration of neutropenia. In each setting, the decrease in morbidity was associated with shorter hospitalisation times and reduced administration of parenteral antibacterial agents. As with another rHuG-CSF, filgrastim, bone pain (non-serious) was the most common adverse reaction to lenograstim therapy. This occurred in 13% of lenograstim recipients and 5% of placebo recipients treated for chemotherapy-induced neutropenia with standard regimens. Lenograstim may facilitate dose optimisation and permit limited dose intensification of standard chemotherapy. Furthermore, the drug, used alone or in combination with chemotherapy, is effective in mobilising peripheral blood progenitor cells (PBPCs) for subsequent reinfusion. The latter is a promising technique which may supplement or ultimately replace BMT for stem cell rescue after myeloablative chemotherapy. However, it has yet to be established whether the dose intensification achievable with lenograstim and/or stem cell rescue has a material effect on relapse-free and survival times. Preliminary data suggest that lenograstim is effective in increasing the neutrophil count in patients with severe chronic neutropenia (Kostmann's syndrome), as well as patients with AIDS or AIDS-related complex with zidovudine-induced neutropenia. Thus, lenograstim, like other CSFs, is a valuable adjunct to cytotoxic chemotherapy for the treatment of nonmyelogenous cancers, including myeloablative regimens followed by stem cell rescue with BMT and/or PBPC infusion. Future clinical experience is likely to confirm the usefulness of the drug in the management of disease-related neutropenia, myeloid disorders and neutropenia in patients with AIDS.
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PMID:Lenograstim. A review of its pharmacological properties and therapeutic efficacy in neutropenia and related clinical settings. 754 35

Severe chronic neutropenia (SCN) is a rare but important cause of recurrent fevers, oropharyngeal ulcerations and severe infections. In three forms of SCN, i.e., congenital neutropenia (Kostmann's syndrome and related syndromes), idiopathic neutropenia (both childhood and adult), and cyclic neutropenia, it is now established that long-term treatment with the hematopoietic growth factor, recombinant human granulocyte colony stimulating factor (rHuG-CSF or Filgrastim), can elevate blood neutrophil counts to the normal range in most patients, with a concomitant reduction in infection-related events including fever, oral ulcerations, antibiotic use and symptoms of inflammation. Treatment with this growth factor causes an increase in the number and maturity of marrow cells of the neutrophilic series; other cell lines are largely unaffected. Marrow stimulation and expansion are reflected by the occurrence of bone pain early in therapy, as well as some increase in spleen size in most cases. Adverse effects of therapy are infrequent in both children and adults, and long-term treatment with daily or every-other-day s.c. injections of rHuG-CSF are well accepted. Because of the risk that some patients with chronic neutropenia may have or develop myelodysplasia and/or leukemia, careful pretreatment evaluations (blood, bone marrow and cytogenetics) and long-term observations are extremely important. An international registry for patients with SCN has been established to maintain records and further investigate these conditions.
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PMID:Hematopoietic growth factors for the treatment of severe chronic neutropenia. 778 81

Most children with acute lymphoblastic leukemia (ALL) are successfully treated by chemotherapy. For those patients, who relapse on therapy, bone marrow transplantation (BMT) is considered most appropriate after a subsequent remission is achieved. Three boys with ALL aged from 9 to 13 years met these criteria and received BMT from their HLA-compatible sisters after marrow ablation with total body irradiation 12 Gy plus high dose cytosine arabinoside 3 gm/m2/12h x 12 doses and graft-versus-host disease (GVHD) prophylaxis with cyclosporine plus short course methotrexate from March 10, 1989 to May 23, 1992. Filgrastim (rhG-CSF) was used to hasten the recovery of granulocyte in one patient. All three patients got full engraftment and two had grade 1 acute GVHD. None of them developed chronic GVHD. Two patients have disease-free survival over 51 and 12 months respectively post BMT without further chemotherapy. One patient died of recurrent refractory leukemia 5 months after BMT. The toxicity of this conditioning regimen included photophobia, conjunctivitis and erythematous skin rashes. One patient who received filgrastim from day 1 to 21 developed severe bone pain. However, this patient had faster recovery of granulocyte count than the other two patients. The preliminary results of this work favors BMT for children with recurrent ALL whose ultimate survival is usually poor when treated with chemotherapy. Further efforts are necessary to investigate new methods for reducing leukemic relapse in ALL patients undergoing BMT.
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PMID:Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in second remission or relapse. 783 80

Filgrastim (rHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) in healthy Japanese volunteers were characterized in detail using two clonal cell culture systems and double-colour flow cytometry to detect multilineage colony-forming cells and subsets of CD34+ cells. The kinetics of PBPC during the administration of filgrastim was studied, and possible differences in the character of progenitor cells relative to given doses of filgrastim were investigated. Filgrastim was administered subcutaneously to normal volunteers for 7 d at doses of 100, 200 or 400 microgram/m2 (10 per cohort). Treatment with 100 or 200 microgram/m2 filgrastim was well tolerated; however, the 400 microgram/m2 dose level was not completed because of bone pain and myalgia. The treatment strikingly mobilized various types of progenitor cells, including highly proliferative megakaryocytic colony-forming cells. The number of progenitor cells peaked on days 5 and 6. The fold increase of circulating progenitor cells from the baseline value in the volunteers treated with 200 microgram/m2 filgrastim was more pronounced than in those treated with 100 microgram/m2. Treatment with 200 microgram/m2 also released the less mature progenitor cells (i.e. mixed colony-forming cells CD34+/33- cells, and CD34+/HLA-DR-cells) into circulation better than the 100 microgram/m2 dose. These results suggest that daily subcutaneous injection with 200 microgram/m/2 filgrastim for 5 d will effectively mobilize, both qualitatively and quantitatively, PBPC in healthy donors.
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PMID:Characterization of peripheral blood progenitor cells (PBPC) mobilized by filgrastim (rHuG-CSF) in normal volunteers: dose-effect relationship for filgrastim with the character of mobilized PBPC. 861 69

Allogeneic peripheral blood stem cell transplantation leads to an earlier engraftment compared to BMT. The feasibility, acceptance and long-term side-effects of G-CSF mobilisation of PBSC in unrelated healthy donors needs to be evaluated. Forty unrelated healthy donors received G-CSF in a dose of 10 microg/kg bodyweight for 5 days and two aphereses were performed. The donors were monitored prospectively. The data were compared to bone marrow harvests from unrelated donors. Almost all stem cell donors reported some side-effects due to Filgrastim application. Bone pain (32), headache (20), chest pain (two) and night sweats (one) were complained of. By taking analgesics, the pain was relieved in most cases. No donor discontinued the filgrastim application. Bone pain and headache resolved within 2-4 days after termination of Filgrastim application. There was, as expected, a seven-fold increase in the number of total WBCs. There were no significant changes of platelet counts during G-CSF application. After 4 weeks haemoglobin concentration and platelet counts showed no significant differences compared to baseline values. The aphereses were mostly tolerated very well. Eighteen donors reported paraesthesia, one donor developed dizziness, two complained of nausea and vomiting. There was a significant decrease in platelet count (242 before, 98 x 10(9)/l after aphereses). Autologous platelets were transfused after the second aphereses in four donors. These data were compared to data from 245 unrelated bone marrow donors, who had on average, 14 days bone pain and tiredness after donation. The G-CSF mobilisation and apheresis of peripheral blood stem cells is an alternative to traditional bone marrow harvesting in unrelated healthy donors. It is well tolerated and the duration of side-effects on average is shorter than after the surgical procedure. So far no long-term effects have been observed in the follow-up.
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PMID:Acceptance and feasibility of peripheral stem cell mobilisation compared to bone marrow collection from healthy unrelated donors. 971 88

An important issue in allogeneic peripheral blood progenitor cell transplantation is the optimization of the regimen of mobilization of progenitor cells from normal donors. It has been shown that for G-CSF doses up to 10 microg/kg/day, a dose-response relationship exists for the degree of progenitor cell mobilization. Formal comparisons with doses higher than 10 microg/kg/day, however, have not been reported. The aim of this study was to compare the mobilization and collection results of two different G-CSF (Filgrastim) schedules: 10 microg/kg/12 h (n = 20; group A) vs 10 microg/kg/24 h (n = 20; group B). Apheresis sessions were started on day 5 (after 4 days of G-CSF). Adverse events consisted of bone pain, headache, and fatigue which required treatment with acetaminophen +/- codeine in both donor groups. Discontinuation of G-CSF administration for intolerable side-effects was not necessary in any case. The increase in peripheral leukocyte and lymphocyte counts x 109/l on day 5 was higher in group A (56.2 (37.1-75.2) and 4.4 (2. 1-14.6), respectively) than in group B (27.5 (13.2-53.9) and 2.6 (1. 9-5.1), respectively) (P < 0.0001 and P = 0.008). Platelets x 109/l decreased in group A from 228 (161-286) before G-CSF administration to 207 (155-328) on day 5 (P = 0.03), whereas no change was observed in group B. Following the first apheresis, a significant decrease in platelet count was observed with both G-CSF schedules without any differences between groups. The number x 106/kg of both nucleated and CD34+ cells collected after the first apheresis session was higher in group A (672 (462-992) and 5.9 (3.4-10.4), respectively) than in group B (427 (319-608) and 3.1 (1.1-6.8), respectively) (P = 0.0003 in both cases). The median number of CD3+cells x 106/kg collected after one apheresis session was similar with both G-CSF schedules (212 (91-430) in group A and 170 (110-291) in group B) (P = NS). In conclusion, the schedule of 10 microg/kg/12 h was well tolerated and resulted in the collection of a higher number of progenitor cells than 10 microg/kg/24 h without increasing the T cell content. This approach could avoid the donor having to undergo a second apheresis, and facilitate further graft manipulation.
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PMID:Efficacy and toxicity of a high-dose G-CSF schedule for peripheral blood progenitor cell mobilization in healthy donors. 1062 34

The efficacy and safety of high-dose lenograstim on CD34 positive (CD34+) cell mobilization into peripheral blood were investigated in 18 healthy male volunteers. The volunteers were divided into 3 lenograstim dose groups of 6 subjects each. Lenograstim was administered at a dose of 2, 5, or 10 micrograms/kg/day, b.i.d. by subcutaneous injection for a total of 5 days. The median peak number of CD34+ cells/microliter of blood was 16.3, 53.9, and 96.6 in the 2, 5, and 10 micrograms/kg/day groups, respectively. A positive correlation was observed between the peak CD34+ level and dose of lenograstim (P = 0.002). The percentage of volunteers achieving more than 50 CD34+ cells/microliter of blood was significantly higher in the 10 micrograms/kg/day group (83.3%, P = 0.010) than in the 2 micrograms/kg/day group (0%). On the subject of safety, at least 1 adverse drug reaction (ADR) was observed in each of the volunteers, and a total of 12, 33, and 45 ADRs were observed in the 2, 5, and 10 micrograms/kg/day groups, respectively. A dose-dependent increase in the number of ADRs was also observed, including an elevation of LDH (P < 0.001), bone pain (P < 0.001), and fatigue (P = 0.008). However, no volunteers required symptomatic treatment or discontinuation of lenograstim. We concluded that administration of lenograstim at a dose of 10 micrograms/kg/day for 5 days is highly effective for CD34+ cell mobilization into peripheral blood and tolerable in healthy volunteers.
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PMID:[Effect of lenograstim (glycosylated recombinant human granulocyte-colony stimulating factor) on peripheral blood stem cell mobilization in healthy volunteers]. 1077 48

Granulocyte colony-stimulating factor (G-CSF) has been used to reduce the duration and/or degree of neutropenia of different etiologies in recent years. In this study, experience with the use of G-CSF (Neupogen, Roche) after 123 courses of highly myelosuppressive chemotherapy administered to 31 (20 female, 11 male) patients with pediatric solid tumors is reported. G-CSF was initiated at a white blood cell (WBC) count of 918 +/- 452/microL (100-2000), at a dose of 7.6 +/- 2.3 micrograms/kg/d (5-14) subcutaneously for 5.2 +/- 2.4 days (2-18). G-CSF was given for afebrile neutropenia after 82 and for febrile neutropenia after 41 courses. Only in two episodes where G-CSF was given for afebrile neutropenia, fever developed. The average hospitalization period for febrile neutropenia was 9.8 +/- 3.3 days (5-20). Chemotherapy could be given on scheduled time and dosage in 90% of the courses in which G-CSF was used for afebrile neutropenia. G-CSF was well tolerated. Bone pain was observed in two patients and urticaria in one patient. In conclusion, G-CSF increased the WBC count effectively, there were only two febrile episodes in 82 courses in children receiving G-CSF for afebrile neutropenia, it was well tolerated, and it was found to be feasible for use in a developing country.
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PMID:Granulocyte colony-stimulating factor in neutropenic, pediatric solid tumor patients following chemotherapy. 1089 13


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