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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The number and growth factor requirements of committed progenitor cells (colony-forming units-granulocyte/macrophage and burst-forming units-erythroid) in three patients with cyclic neutropenia (two congenital, one acquired) were studied before and during therapy with recombinant human granulocyte colony-stimulating factor (G-CSF; 3 to 10 micrograms/kg/d). When the patients with congenital disease were treated with G-CSF, the cycling of blood cells persisted, but the cycle length was shortened from 21 days to 14 days, and the amplitude of variations in blood counts increased. There was a parallel shortening of the cycle and increase of the amplitude of variations (from two- to three-fold to 10- to 100-fold) in the number of both types of circulating progenitor cells in these two patients. In the patient with acquired cyclic neutropenia, cycling of both blood cells and progenitors could not be seen. In cultures deprived of fetal bovine serum, erythroid and myeloid bone marrow progenitor cells from untreated patients and from normals differed in growth factor responsiveness. As examples, maximal growth of granulocyte/macrophage (GM) colonies was induced by granulocyte/macrophage (GM)-CSF plus G-CSF in the patients, whereas a combination of GM-CSF, G-CSF and interleukin-3 (IL-3) was required in the normals, and erythropoietin alone induced fourfold more erythroid bursts from cyclic neutropenic patients than from normal donors (46% versus 11% of the maximal colony number, respectively). The growth factor responsiveness of marrow progenitor cells slightly changed during the treatment toward the values observed with normal progenitors. These results indicate that treatment with G-CSF not only ameliorated the neutropenia, but also increased the amplitude and the frequency of oscillation of circulating progenitor cell numbers. These data are consistent with the hypothesis that G-CSF therapy affects the proliferation of the hematopoietic stem cell.
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PMID:Hematopoietic progenitors in cyclic neutropenia: effect of granulocyte colony-stimulating factor in vivo. 169 89

The synergism of combined high-dose etoposide with standard dose cisplatin (HD-EP) was evaluated in 20 patients who had relapsed after treatment of small cell lung cancer. Each patient was given etoposide at 500 mg/m2/day on days 1 to 3 and cisplatin at 80 mg/m2 (two patients given 120 mg/m2) on day 1; autologous bone marrow was not transplanted. Five patients were given recombinant human granulocyte colony-stimulating factor (rhG-CSF, 50 micrograms/m2) in an attempt to reduce HD-EP induced neutropenia. The overall response was 50% (9 of 18); one complete response (6%), eight partial responses (44%), seven no change (39%), and two progressions of disease (11%). Of the 18 evaluable patients, 12 had been treated with regimens of conventional doses of etoposide with conventional doses of cisplatin or carboplatin, and of these, five (42%) achieved a partial response. The median duration of response was 8.4 weeks (range, 5.3 to 17.7) and the median survival time was 20.3 weeks (range, 1.6 to 91). All of the patients developed severe myelosuppression; rhG-CSF did not shorten the period of the leukopenia. Mucositis and liver dysfunction were the major nonhematologic manifestations of toxicity. Two treatment-related deaths resulted from sepsis. These results suggest that the activities of high doses etoposide with standard doses of cisplatin are synergistic against small cell lung cancer.
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PMID:Evaluation of high-dose etoposide combined with cisplatin for treating relapsed small cell lung cancer. 169 57

In an attempt to evaluate rG-CSF for preventing and reducing the period of chemotherapy-induced neutropenia, phase II studies of the agent, KRN 8601, have been conducted in patients receiving chemotherapy for lung cancer. In the cooperative study, 53 patients with lung cancer were fully evaluated. The chemotherapy regimen for the patients enrolled in the study was not specified, but an identical regimen with an identical dose and schedule was mandatory for the first cycle in which the patients did not receive the rG-CSF, and for the following cycles in which they received it after completion of chemotherapy for 14 days consecutively. Patients were allocated to receive the agents either at a dose of 100, 200 or 400 micrograms/m2 via intravenous drip infusion; or at as ub cutaneous dose of 25, 75, or 125 micrograms. In the author's study, all the 9 patients with non-small cell lung cancer received a 3-drug combination of vindesine, ifosfamide, and cisplatin(VIP) at an identical dose throughout the cycles. The rG-CSF was administered on the second and the following cycles at a dose of 100 micrograms/m2, subcutaneously, in the same manner as the above. Myelogram and neutrophil functions, i.e., superoxide anion production, chemotactic, and phagocytic activity, were serially determined in these patients. With intravenous dose of 100 micrograms/m2, the rG-CSF considerably elevated the nadir count of neutrophils and significantly reduced the duration of neutropenia. Subcutaneously administered rhG-CSF at 75 micrograms doses did as with intravenous infusion. The optimal dose of the agent in conventional chemotherapy was estimated to be 100 micrograms/m2 when infused intravenously, and 75-125 micrograms subcutaneously. Subcutaneously administered rG-CSF at a dose of 100 micrograms/m2 did not contribute to spare the nadir count of neutrophils, but contributed toward reducing the period of neutropenia induced by the 3-drug combination which was much more myelosuppressive than conventional regimens. Thus, the optimal dose of the agent should be determined according to the dose-intensity of chemotherapy. Peripheral neutrophils obtained after recovery from VIP-induced neutropenia showed a normal activity in superoxide anion production and mobility when combined with rG-CSF, although the activity showed a trend to remain subnormal in the recovered neutrophils without rG-CSF. In conclusion, rG-CSF considerably reduces the neutropenia and possibly reduces infections caused by intensive chemotherapy. Hereafter, clinical trials must determine whether rG-CSF improve the therapeutic outcomes of patients receiving chemotherapy in terms of response rate and patient survival.
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PMID:[Effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) on chemotherapy-induced neutropenia in patients with lung cancer]. 169 62

Myelosuppression following intensive chemotherapy in cancer patients is associated with increased morbidity and mortality. Hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), alone or in combination with interleukin-1 (IL-1), have been shown to counteract myelosuppression resulting from some, but not all, chemotherapeutic regimens. In an attempt to apply these findings to intensive therapy with proliferation-dependent chemotherapeutic drugs such as fluorouracil (5-FU), we investigated combination biochemotherapy in a murine model. Female CD8F1 [(BALB/c X DBA/8)F1] mice bearing first-passage transplants of spontaneous CD8F1 breast tumors were treated intraperitoneally once a week for 3 successive weeks with a course of 5-FU alone or with a course of 5-FU in combination with recombinant human interleukin-1 beta (rHuIL-1 beta) alone or in combination with CSFs. rHuIL-1 beta alone or in combination with rHuG-CSF or recombinant murine GM-CSF significantly improved tumor growth inhibition (60% vs. 90%) and survival (20% vs. 90%-100%), increased the maximally tolerated dose of 5-FU, accelerated recovery of neutrophil counts in peripheral blood, and reduced duration of significant neutropenia and loss of body weight (29% vs. 10% loss). Clinical trials of IL-1 have been initiated in patients with advanced cancer receiving multiple courses of high-dose 5-FU.
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PMID:Hematologic effects of interleukin-1 beta, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor in tumor-bearing mice treated with fluorouracil. 169 5

Despite the emergence of newer antibiotic treatments, group B streptococcal infection still carries a high mortality rate in the newborn and is characterized by reduced neutrophil proliferative pools, neutrophil storage pools, neutropenia, and polymorphonuclear cell dysfunction. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) has recently been demonstrated to induce neutrophilia and modulate neutrophil proliferative pools and neutrophil storage pools in the newborn rat. We therefore investigated the adjuvant effect of rhG-CSF given to group B streptococcus (GBS) septic Sprague-Dawley newborn (less than 36 h) rats treated with and without antibiotic therapy. After inoculation of GBS, a GBS survival curve established the LD50 at 50 h to be approximately 3 X 10(6) organisms/gm. Newborn rats were divided into four treatment groups after GBS inoculation. rhG-CSF was administered at the same time as GBS inoculation. At 24 h, there was approximately 100% survival in all groups. However, by 72 h after GBS inoculation, there was a significant difference in survival. Group 1, PBS/Alb, had a survival rate of 4%; group 2, rhG-CSF, 9%; group 3, antibiotics, 28%; and group 4, antibiotics plus rhG-CSF, 91% (p less than or equal to 0.001). Additionally, when rhG-CSF was administered prophylactically (6 h before GBS), a similar significant synergistic effect in survival was demonstrated with granulocyte colony stimulating factor plus antibiotics versus antibiotics alone (70 versus 10%) (p less than or equal to 0.01). These preliminary data suggest that either simultaneous or prophylactic pulse administration of rhG-CSF may have a synergistic and protective effect on survival in antibiotic-treated experimental GBS in the neonatal rat.
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PMID:Prophylactic or simultaneous administration of recombinant human granulocyte colony stimulating factor in the treatment of group B streptococcal sepsis in neonatal rats. 169 23

Infantile genetic agranulocytosis (IGA) has a high morbidity and mortality rate due to severe neutropenia. The pathogenetic mechanisms of this syndrome have not been elucidated. However, a recent clinical trial with recombinant human granulocyte-colony-stimulating factor (rhG-CSF) has shown a dramatic increase in the absolute neutrophil count in patients with IGA. This suggests that these patients have either a lack of granulocyte-colony-stimulating factor (G-CSF) or have a defect in the G-CSF receptors. A clinical trial of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) in an infant with IGA is reported in this article. A marked eosinophilic response was observed without any increase in the absolute neutrophil count (ANC). In an effort to elucidate the pathogenetic mechanism underlying IGA, we examined (a) the in vitro response of patient's CFU-GM to rhGM-CSF and to rhG-CSF and (b) the ability of patient's monocytes to produce G-CSF. Our results tend to support the thesis that the defect in IGA is at the G-CSF receptor level. We also found a lack of correlation between in vivo and in vitro response to rhGM-CSF.
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PMID:Congenital neutropenia: a case study. 169 74

Granulocyte colony-stimulating factor stimulates the proliferation and differentiation of progenitor cells committed to the neutrophil lineage, and it has been shown to improve survival to bacterial challenge in neutropenic mice. We studied recombinant human granulocyte colony-stimulating factor (rhG-CSF), cloned from bladder cell carcinoma line 5637, in a nonneutropenic infection model of Streptococcus pneumoniae pulmonary infection in splenectomized and sham-operated control mice. The rhG-CSF improved survival in the splenectomized mice but not in the sham-operated mice. Circulating leukocyte counts were greatest for the rhG-CSF-treated splenectomized mice compared with all other groups, presumably due to a loss of splenic sequestration. Clearance of live pneumococci from mouse lung pairs was impaired after splenectomy. The rhG-CSF improved lung clearance in both splenectomized and sham-operated mice compared with saline solution-treated controls. The number of live pneumococci recovered from tracheobronchial lymph nodes at 24 hours after aerosol challenge was greatest in the splenectomized mice vs sham-operated mice. Decreased numbers of viable pneumococci were recovered from tracheobronchial lymph nodes from the rhG-CSF-treated splenectomized mice and the sham-operated mice vs saline solution-treated controls. The rhG-CSF may be a useful adjuvant for treating infections in individuals with immunologic dysfunctions other than neutropenia.
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PMID:Protective effect of recombinant human granulocyte colony-stimulating factor against pneumococcal infections in splenectomized mice. 169 96

Cyclic hematopoiesis in gray collie dogs is a stem cell disease in which abnormal regulation of cell production in the bone marrow causes cyclic fluctuations of blood cell counts. In vitro studies demonstrated that recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and granulocyte colony stimulating factor (G-CSF) all stimulated increases in colony formation by canine bone marrow progenitor cells. Based on these results, gray collie dogs were then treated with recombinant human (rh) GM-CSF, IL-3, or G-CSF subcutaneously to test the hypothesis that pharmacologic doses of one of these hematopoietic growth factors could alter cyclic production of cells. When recombinant canine G-CSF became available, it was tested over a range of doses. In vivo rhIL-3 had no effect on the recurrent neutropenia but was associated with eosinophilia, rhGM-CSF caused neutrophilia and eosinophilia but cycling of hematopoiesis persisted. However, rhG-CSF caused neutrophilia, prevented the recurrent neutropenia and, in the two animals not developing antibodies to rhG-CSF, obliterated periodic fluctuation of monocyte, eosinophil, reticulocyte, and platelet counts. Recombinant canine G-CSF increased the nadir neutrophil counts and amplitude of fluctuations at low doses (1 micrograms/kg/d) and eliminated all cycling of cell counts at high doses (5 and 10 micrograms/kg/d). These data suggest significant differences in the actions of these growth factors and imply a critical role for G-CSF in the homeostatic regulation of hematopoiesis.
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PMID:A comparison of treatment of canine cyclic hematopoiesis with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF interleukin-3, and canine G-CSF. 169 46

The cause of chronic idiopathic neutropenia (CIN) is unknown. Recently recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been purified. Many studies of effects of rhG-CSF on the patients with neutropenia have been undertaken. We examined changes in neutrophil counts and functions after the administration of rhG-CSF in a patient with CIN. Six hours after the intravenous administration of 40 micrograms of rhG-CSF, neutrophil counts were raised from 90 to 1570/microliters, and the increased neutrophils functioned normally; chemotaxis, phagocytosis and O2(-) generation. It is suggested that rhG-CSF is beneficial for the treatment of infection in patients with CIN.
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PMID:[Changes in neutrophil counts and functions after the administration of recombinant human granulocyte colony-stimulating factor in a patient with chronic idiopathic neutropenia]. 169 26

The number of circulating hematopoietic progenitor cells was determined during 47 courses of chemotherapy in 23 patients with hematopoietic malignancies. rhG-CSF was given subcutaneously to 14 patients to rescue chemotherapy-induced neutropenia following 22 courses of chemotherapy. The mean numbers of CFU-GM in patients with malignant lymphoma (ML), acute leukemia (AL) and myeloma (MM) were 56.0 +/- 58.8 (mean +/- SD), 46.7 +/- 66.0 and 11.0 +/- 11.1 CFU-GM/ml, respectively. The number of CFU-GM in MM was significantly less than in normal subjects (51.2 +/- 30.6 CFU-GM/ml). The number of CFU-GM in PB in all patients began to rise between 2 days before and 8 days after nadir of WBC count, and then reached the peak at the subsequent 5 days. The peak values of CFU-GM in ML, AL and MM were 711.3 +/- 974.7, 660.0 +/- 374.7 and 403.6 +/- 232.5 CFU-GM/ml, respectively, but there was no statistical difference among them. When ML patients were treated with rhG-CSF, the CFU-GM peak values increased as much as 5.5-folds compared with those following chemotherapy only. However, neither the period from nadir to start of increase in the CFU-GM count nor the time of the CFU-GM peak showed any significant change. These results indicate that the administration of rhG-CSF makes it possible to increase the number of circulating progenitor cells. It appears possible in most of the patients with hematopoietic malignancies to harvest the sufficient number of progenitor cells which are necessary for autologous blood stem cell transplantation.
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PMID:[Kinetics of circulating hematopoietic stem cells following chemotherapy in patients with hematopoietic malignancies]. 169 29


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