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)

Based on the results of preclinical and in vitro studies demonstrating enhanced granulocytic proliferation and differentiation induced by granulocyte-monocyte and granulocyte-colony stimulating factors (GM-CSF and G-CSF), these recombinant human haemopoietic growth factors have been used to treat cytopenic patients with myelodysplastic syndromes (MDS). Laboratory investigations have shown responsiveness of enriched haemopoietic precursors in vitro to the proliferative and granulocytic differentiative stimuli of G-CSF, generally without increased clonal regeneration. To date, five short-term phase I/II clinical trials using GM-CSF have demonstrated that 38 of 45 treated patients had improvements in neutrophil counts, 14 had increased reticulocyte counts, with three of these patients having decreased red blood cell transfusion requirements, and eight had a transient increase in platelets. In 12 patients an increase in marrow and/or peripheral blood blasts was noted. Seven patients progressed to acute myeloid leukaemia (AML), particularly patients with greater than 15% marrow blasts. In a longer term study, five patients received GM-CSF for two to nine weeks, although only one maintained increased neutrophil counts, one developed antibodies to GM-CSF and one's condition evolved into AML. Eighteen patients have been treated for two months in phase I/II clinical trials with G-CSF, 16 of whom had normalization of neutrophil counts with improved marrow maturation, five had increased reticulocyte counts with three having decreased transfusion requirements, four had transient increases in blasts and no substantial changes in platelet counts were noted. Eleven patients have received maintenance therapy with G-CSF for 6-16 months and 10 had persistent increases in neutrophil counts with enhanced marrow myeloid maturation. Decreased infectious episodes were noted in these patients at times at neutrophil improvements. Four of the 18 patients have subsequently developed AML after 6-16 months. Both CSFs were well tolerated, although the incidence of fever, myalgias and bone pain was more prominent in patients receiving GM-CSF at higher doses. In vitro correlates with these in vivo results were demonstrated as laboratory studies showed that G-CSF had greater myeloid differentiative and less proliferative effects for MDS marrow than did GM-CSF. Marrow cytogenetic studies after treatment generally indicated persistence of the initial normal and/or abnormal clones. These studies have demonstrated that both G-CSF and GM-CSF improve neutrophil counts in a high proportion of patients with MDS and that chronic administration of G-CSF elicits persistent neutrophil responses and may decrease infections. Phase III controlled trials are required to determine whether the natural history of this disorder will be altered by use of colony stimulating factors.
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PMID:The use of haemopoietic growth factors in the treatment of myelodysplastic syndromes. 227 14

The genes for a number of growth factors that stimulate human hematopoietic and lymphoid cells in vitro have recently been cloned and recombinant molecules provided for clinical trials. For three of these (erythropoietin, G-CSF, and GM-CSF), phase I and II studies have been completed and promising results have been obtained. Of particular relevance to the field of bone marrow transplantation (BMT) has been the finding that G-CSF and GM-CSF could shorten the period of neutropenia in patients treated with chemotherapy, including regimens requiring BMT support. Doses of up to 240 micrograms/m2 of GM-CSF have been well tolerated and have increased the peripheral blood neutrophil count in a dose-dependent manner. At higher doses, eosinophils and monocytes were also increased. A continuous infusion over at least 2 h was found to be superior to bolus administration in terms of both efficacy and reduced side effects. These have usually been mild, but bone pain, headache, fatigue and elevated temperature have been encountered. The rise in neutrophil numbers shortly after initiating treatment with GM-CSF is probably due to neutrophil demargination. After a few days increased bone marrow cellularity has also been noted. In addition to these effects on cell numbers, enhancement of granulocyte and monocyte functions has been documented. However, a major concern with the use of G-CSF and GM-CSF in cancer patients, particularly those with hematopoietic malignancies, is the potential of these molecules to stimulate malignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony stimulating factors. 245 88

A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.
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PMID:Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study. 247 58

Granulocyte--colony stimulating factor (G-CSF, filgrastim) is a glycoprotein hormone of the hematopoietin family that primarily influences the proliferation and differentiation of neutrophilic granulocytic precursors. As with all glyco-protein hormones, G-CSF interacts with target cells by binding to specific cell-surface receptors. It stimulates proliferation, differentiation and activation of cells of the neutrophil--granulocyte lineage and has been investigated as therapy for patients with various neutropenic conditions. A major use for recombinant G-CSF therapy will be in ameliorating the neutropenia which follows cytoreductive chemotherapy. The increase in neutrophils produced by this factor render it a useful treatment for conditions such as congenital, acquired and cyclic neutropenias. It may be an effective therapy in myelodysplasia and aplastic anaemia. G-CSF is also useful in accelerating the recovery of transplanted bone marrow in patients with leukaemia, lymphoma and solid tumors. G-CSF is well tolerated. The most frequently reported adverse effect is mild to moderate bone pain.
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PMID:[Biological properties and clinical application of filgrastim (G-CSF)]. 750 84

One hundred patients with advanced carcinoma undergoing highly cytotoxic chemotherapy were enrolled in a prospective randomized trial comparing subcutaneous G-CSF, thymopentin, a combination of the two, and placebo as preventive treatment of febrile leukopenia. Data from this study show that G-CSF was very active in reducing the incidence of chemotherapy-related fever and leukopenia as compared to placebo (22% versus 64%). This difference was statistically highly significant (P < 0.001). Thymopentin was associated with a reduction in febrile episodes as compared to placebo (52% versus 64%), but this difference did not reach statistical significance. Moreover, the addition of thymopentin to G-CSF did not result in a statistically significant improvement of results obtained with G-CSF alone. Similar results were achieved for fungal infections. Tolerance to thymopentin was excellent, while less than 9% of patients on G-CSF treatment complained of mild nausea and generalized bone pain.
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PMID:A prospective randomized trial of thymopentin versus granulocyte--colony stimulating factor with or without thymopentin in the prevention of febrile episodes in cancer patients undergoing highly cytotoxic chemotherapy. 751 41

Recombinant human granulocyte colony-stimulating factor (rhGCSF) has been commercially available for two years; yet unanswered questions need to be substantiated by clinical trials. The most extensively studied clinical application has been in chemotherapy-induced neutropenia. GCSF accelerates neutrophil recovery after bone marrow transplant, mobilizes bone marrow progenitor cells into peripheral blood harvesting then transplanted as supportive measures in patients undergoing intensive chemotherapy, and accelerates neutrophil recovery in patients with acute leukemias. GCSF is generally well-tolerated with only mild to moderate bone pain. Mild reversible elevation in lactate dehydrogenase, alkaline phosphatase, and uric acid has been reported. As data are obtained from ongoing trials, GCSF's clinical role will be expanded and better defined.
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PMID:Granulocyte colony stimulating factor. 752 57

Allogeneic transplantation of peripheral blood progenitor cells (PBPC) makes the general anaesthesia of the donor unnecessary and may result in more rapid engraftment and faster recovery of the immune system. We have studied G-CSF-mediated PBPC mobilization in healthy donors and analysed the cellular composition of the resulting PBPC grafts. PBPC grafts were obtained from nine healthy donors (18-67 years old) for allogeneic or syngeneic transplantation. Six donors received 10 micrograms/kg G-CSF per day, the others 5-6 micrograms/kg. Mobilization and harvesting were well tolerated except for moderate bone pain which occurred in all donors primed with 10 micrograms/kg. With 10 micrograms/kg, a 31-fold (9-62) enrichment of circulating CD34+ cells was observed with peak values constantly occurring on day 5 after the start of G-CSF administration. Starting harvest on day 5, one to three collections on consecutive days yielded 5.5 x 10(6)/kg (0.9-10.7) CD34+ cells, 219 x 10(6)/kg (106-314) T cells, and 34 x 10(6)/kg (23-67) NK cells per 10 litres leukapheresis volume. Altogether, PBPC grafts contained 3 times more CD34+ cells, 7 times more T cells, and 20 times more NK cells than five allogeneic marrow grafts that were analysed for comparison. The yield of CD34+ cells per 10 litres apheresis volume as well as the height of the CD34+ peak in peripheral blood were inversely correlated to the age of the donor. In the donors primed with 5-6 micrograms/kg G-CSF the increase of circulating CD34+ cells (4-7-fold enrichment) and the CD34+ cell yield per 10 litres leukapheresis volume (1 x 10(6)/kg [0.8-2.2]) was much smaller compared with the 10 micrograms/kg group. In conclusion, sufficient amounts of PBPC capable of restoring haemopoiesis in allogeneic recipients can be mobilized safely by administration of G-CSF (10 micrograms/kg s.c. for 5 d) in healthy donors, and harvested with one or two leukapheresis procedures. Whether the large numbers of T-cells and NK cells that are contained in the collection products may influence graft-versus-host and graft-versus-leukaemia reactivities of PBPC grafts remains to be determined.
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PMID:G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation: safety, kinetics of mobilization, and composition of the graft. 752 48

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.
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PMID:Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor. 769 Dec 44

The difference between the effects of administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was studied in 39 children with neutropenia secondary to chemotherapy (absolute neutrophil count (ANC) less than 1,500/microliters. The children were divided into two groups. The first group (G-CSF) included 25 children (12 with acute lymphoblastic leukemia [ALL]-non-Hodgkin's lymphoma [NHL] and 13 with solid tumors) and the second group (GM-CSF) included 14 children (5 with ALL-NHL and 9 with solid tumors). All 39 children received of either G-CSF or GM-CSF (5 micrograms/kg/day) subcutaneously at the end of each chemotherapy course for a maximum duration of 14 days. The effect of G-CSF and GM-CSF on the ANC, the antibiotic therapy administration, and the length of hospital stay were studied for both groups at two cycles of chemotherapy. During both cycles a faster rise of ANC was observed in the children of the first group (G-CSF) compared with those of the second group (GM-CSF), but there was no difference in either the incidence of antibiotic therapy administration between the two groups (26% vs 25%) or the length of hospitalization. Both growth factors were well tolerated by all children studied with minimal side effects observed (including bone pain with G-CSF in 2 of 25 children and pruritus with GM-CSF in 1 of 14). We conclude that G-CSF reduces the duration of neutropenia more than does GM-CSF, but the incidence of severe infection and the duration of hospitalization do not differ between children receiving either G-CSF or GM-CSF.
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PMID:Efficacy of recombinant human granulocyte colony-stimulating factor and recombinant human granulocyte-macrophage colony-stimulating factor in neutropenic children with malignancies. 858

The effects of both daily G-CSF administration and subsequent peripheral blood progenitor cell collection (PBPCC) by apheresis on 20 healthy adult donors were studied. All received daily G-CSF (filgrastim) 10 micrograms/kg for 5-7 days by subcutaneous injection. G-CSF administration was well tolerated, except for moderate bone pain and headache. Peak values of CD34+ cells were observed on days 5 (n = 12) or 6 (n = 8). In all donors a significant increase in CD3+, CD4+, CD8+, CD19+, and NK cells was observed on day 5 in relation to the baseline values. CD4/CD8 lymphocyte ratio was unmodified by G-CSF. None of the donors required a central venous line for PBPCC. Immediately after PBPCC, a platelet count below 100 x 10(9)/1 was observed in nine of 18 cases, although in all donors platelet counts were over 100 x 10(9)/1 7 days later. A lymphocytopenia on day 7 following PBPCC was observed, although there was a tendency to achieve baseline values 30-90 days after the procedure. Mean numbers ( +/- SD) of collected cells x 10(6)/kg after a median of two (1-4) apheresis sessions and a median of 20 1 (10-40) processed were: CD34+ 5.5 ( +/- 2.3), CD3+ 326 ( +/- 105), CD4+ 207 ( +/- 64), CD8+ 164 ( +/- 60), CD19+ 88 ( +/- 32), and NK cells 32 ( +/- 14). We conclude that G-CSF administration to healthy donors is a well-tolerated procedure which is associated with (a) obtaining a high number of hematopoietic progenitor cells, and (b) a significant increase in T, B, and NK cells in donors' blood. In addition, PBPCC by apheresis results in a moderate, rapidly reversible, and clinically irrelevant thrombocytopenia and a moderate lymphocytopenia, which tends to resolve within 3 months following the procedure.
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PMID:Effects of G-CSF administration and peripheral blood progenitor cell collection in 20 healthy donors. 862 83


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