UMLS:C0027947 - FACTA Search

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

In four cases of severe neutropenia of unknown origin we found a strong inhibition of the growth of granulocyte-macrophage (GM) progenitor cells. The development of GM colonies in culture (GM-CFU-c) was more than 80% reduced in comparison to the control group. In particular, the interleukin 3-(IL-3) and granulocyte macrophage colony-stimulating factor-(GM-CSF) dependent growth was affected; a combination of growth factors (IL-3, GM-CSF, and G-CSF, the granulocyte colony-stimulating factor) resulted in a less reduced growth. The findings were primarily compatible with drug-induced bone marrow failure. Among the medications given to the patients, famotidine, an H2-receptor blocker, was discussed as an agent which possibly triggers off this process. After the withdrawal of famotidine, in three cases a continual increase of the growth of GM precursors was detected, reaching the normal level 7-17 days later. In one case, further investigations of the progenitor cells could not be carried out due to the death of the patient, but the rapid increase of neutrophils in the peripheral blood after withdrawal of famotidine pointed to the recovery of hematopoiesis. In vitro studies showed that famotidine, depending on the dose, inhibits the single growth factor-dependent colony growth (IL-3, GM-CSF, or G-CSF) of bone marrow progenitors from a concentration as low as 10 micrograms/ml. With the combination of all three growth factors only slight inhibitory effects were detectable (up to 150 micrograms/ml famotidine). These results indicate that famotidine, in common with other H2-receptor antagonists, can affect hematopoietic progenitor cells. However, the plasma concentration of famotidine normally used in ulcer therapy does not seem to influence the hematopoiesis. Apparently, the progenitor cells of only a few patients possess a higher sensitivity to the blockade of H2-receptors at this concentration of famotidine. This was demonstrated in one case (patient 3) 2 years after the patient had recovered from famotidine-induced neutropenia. The growth of peripheral myeloid, erythroid, and multilineage progenitor cells of this patient was remarkably reduced even at famotidine concentrations of 0.1-5.0 micron/ml whereas in the control group no inhibition was detected at these famotidine concentrations. Again, the IL-3-dependent colony formation was more affected than in the case of the combination of IL-3, GM-CSF, and G-CSF. After the removal of accessory cells the inhibitory effect of famotidine persisted, demonstrating that accessory cells do not play a major role in this process.
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PMID:The growth capacity of hematopoietic progenitor cells in severe neutropenia induced by famotidine. 162 58

Seventeen patients with small cell lung cancer were entered into a dose ranging phase I-II study using rhGM-CSF (Glaxo). In the phase I study patients received 50, 150, 300 or 500 micrograms/m2 GM-CSF for 10 days by daily subcutaneous injection. Full blood counts were performed thrice weekly. After 4 days off all therapy patients then received chemotherapy with doxorubicin 50 mg/m2 i.v. bolus, day 1, ifosfamide 5 g/m2 with mesna 5 g/m2 over 24 h by continuous infusion followed by mesna 3 g/m2, and etoposide 120 mg/m2 i.v. on days 1-3. A total of six courses of chemotherapy were given. In the phase II study patients received the same dose of GM-CSF as in the phase I. GM-CSF was given 24 h after the last dose of chemotherapy for 14 days. Full blood counts were checked thrice weekly and the incidence of infections noted. Patients were randomised to receive GM-CSF with either odd or even courses of chemotherapy. The leucocyte count rose from a mean of 8.7 to 21.6 x 10(9)/l at the 50 micrograms/m2 GM-CSF dosage and from 11.4 to 39.4 x 10(9)/l at the 500 micrograms/m2 dosage during the phase I study. Phase I toxicity was: bone pain in 65% of patients, rash in 47%, fever in 24%, lethargy in 12% and diarrhoea in 12%. In the phase II study the duration of neutropenia was less during the chemotherapy courses with GM-CSF (p = 0.04) but the number of infections was similar.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant human GM-CSF in small cell lung cancer: a phase I/II study. 165 15

In three consecutive pilot studies the effect of recombinant human granulocyte/macrophage-colony-stimulating factor (rhGM-CSF) on haematopoetic recovery after chemotherapy in patients with small-cell lung cancer was investigated. In study I, 20 patients received AIO chemotherapy (A, Adriamycin 25 mg/m2 on days 1 + 2; I, ifosfamide 2 g/m2 on days 1-5; O, vincristine 2 mg on day 1) at 4-week intervals either with or without rhGM-CSF (250 micrograms/m2 sc) from day 8 until recovery of leucocytes. Neither the degree nor the duration of myelosuppression was markedly influenced by rhGM-CSF. Suggesting that these disappointing results were caused by the late onset of GM-CSF application, in the following study we shortened chemotherapy to 3 days and started with GM-CSF on day 4. The main objective of this study was to test whether the earlier administration of GM-CSF allowed treatment intervals to be reduced or the dose to be escalated. After 10 patients had received a starting dose of AIO (A, 50 mg/m2 on day 1; I, 2 g/m2 on days 1-3; 0,2 mg on day 1) alternating with cisplatin (90 mg/m2 on day 1) and etoposide (150 mg/m2 on days 1-3), the dose of ifosfamide and etoposide was escalated to 2.5 g/m2 on days 1-3 and 200 mg/m2 on days 1-3 in the next 10 patients. Treatment was given at 2-week intervals when leucocytes were greater than 3500/mm3 and thrombocytes were greater than 100,000 mm3 on day 14. At each dose level patients were randomized to receive either rhGM-CSF 250 micrograms/m2 s.c. on days 4-12 or no GM-CSF. In this study, rhGM-CSF markedly shortened the duration of leukopenia. Reinstitution of chemotherapy on day 15 was possible at dose level 1 in 1/4 patients without and in 3/4 patients with GM-CSF, and at dose level 2 in 0/5 patients without and in 5/5 patients with GM-CSF. However, the degree of myelosuppression was not improved by GM-CSF. In a third study we tried to apply rhGM-CSF simultaneously with chemotherapy. After 3 patients had received GM-CSF starting on day 1 concurrent to AIO chemotherapy, we noticed an increase of myelosuppression with prolonged neutropenia and thrombocytopenia and stopped this investigation. Considering all patients included in these three consecutive pilot studies, there is no difference in response rates and survival between patients with and without rhGM-CSF treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of rhGM-CSF on haematopoietic reconstitution after chemotherapy in small-cell lung cancer. 166 93

The therapeutic evaluation of rG.CSF has been studied on neutropenic patients receiving lung cancer chemotherapy with focusing the change in the absolute neutrophil counting (ANC) in the patients during chemotherapy and subsequent rG.CSF treatment by daily dosing either at 0.4, 2.0, 5.0 and 10.0 micrograms/kg intravenously or at 2.0 and 5.0 micrograms/kg subcutaneously. The daily rG.CSF dosing for 14 consecutive days was performed on the patients upon completion of the 28-day chemotherapy for lung cancer. As a result, remarkable recovery of ANC was observed in the patients administered at doses of more than 5 and 2.0 micrograms/kg intravenously and subcutaneously, respectively. Additionally, the shortening of the neutropenia (ANC: below 1,000/cmm) was observed in the patients at doses of not less than 2.0 micrograms/kg in both administration routes. In conclusion, rG.CSF treatment demonstrates the completion and/or shortening of the chemotherapy cycle for lung cancer at a subcutaneous dose of 2.0 micrograms/kg and at a intravenous dose of 5.0 micrograms/kg. No adverse drug effects were observed in all patients during the study.
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PMID:[Clinical effect of recombinant human G-CSF on neutropenia induced by chemotherapy for lung cancer. rG.CSF Cooperation Study Group]. 168

Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia secondary to a maturational arrest at the level of promyelocytes. We treated five patients with SCN with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 42 days and subsequently, between 1 and 3 months later, with rhG-CSF for 142 days. The objective was to evaluate the safety and ability of these factors to elicit a neutrophil response. rhGM-CSF was administered at a dose of 3 to 30 micrograms/kg/d (30 to 60 minutes, intravenously). In all patients, a specific, dose-dependent increase in the absolute granulocyte counts was observed. However, in four patients this increase was due to an increase in eosinophils, and in only one patient it was due to an increase in the absolute neutrophil counts (ANC). Subsequently, all patients received rhG-CSF at a dose of 3 to 15 micrograms/kg/d subcutaneously. In contrast to rhGM-CSF treatment, all five patients responded to rhG-CSF during the first 6 weeks of treatment with an increase in the ANC to above 1,000/microL. The level of ANC could be maintained during maintenance treatment. In one patient, the increase in ANC was associated with an improvement of a severe pneumonitis caused by Peptostreptococcus and resistant to antibiotic treatment. No severe bacterial infections occurred in any of the patients during CSF treatment. All patients tolerated rhGM-CSF and rhG-CSF treatment without severe side effects. These results demonstrate the beneficial effect of rhG-CSF in SCN patients.
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PMID:Differential effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in children with severe congenital neutropenia. 168 95

The clinical usefulness of KRN 8601 (rhG-CSF) was evaluated in patients with neutropenia induced by chemotherapy for non-Hodgkin lymphoma in a double-blind study. The same chemotherapeutic regimens repeated for twice in 3 to 4 weeks interval. During the first cycle of chemotherapy, changes of leukopenia (neutropenia) were observed, and KRN 8601 at a dose of 75 micrograms/body or placebo was started to administer subcutaneously 72 hours after the termination of the second cycle and continued for 14 days. Elevations of nadirs of absolute neutrophil counts (ANC) and significant shorting of neutropenic periods of ANC below 2,000/mm3 were observed with patients given KRN 8601. KRN 8601 is significantly superior over placebo (p less than 0.0001), while overall safety evaluation showed no significant difference between the two groups. All the above results indicate that KRN 8601 is extremely usefull for the neutropenia induced by chemotherapy.
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PMID:[A phase III study of KRN 8601 (rhG-CSF) on neutropenia induced by chemotherapy for malignant lymphoma--a multi-institutional placebo controlled double-blind comparative study]. 168 88

Administration of human granulocyte colony-stimulating factor (hG-CSF) to mice with cyclophosphamide (CPA)-induced neutropenia for 4 consecutive days from the day after the CPA dosing (100 mg/kg) resulted in a dose-dependent increase in the peripheral blood neutrophil count 6 hours after the final hG-CSF injection. Within the hG-CSF dose range of 0.1 to 10 micrograms per mouse per day, there was a strong linear relationship (r greater than .9) between the logarithm of the dose and the peripheral blood neutrophil count in the treated mice. Using the same hG-CSF preparation, 38 experiments indicated that the regression lines are highly reproducible. Such an association never occurred with intact mice, and 100 mg/kg of CPA induced the highest response to hG-CSF. This linear relationship between the two variables allows us to determine the biologic potency of a test hG-CSF preparation relative to a reference standard using a parallel line assay, with a coefficient of precision of around .2. When assayed by this bioassay procedure, which we have termed CPA-mouse assay, natural hG-CSF and recombinant hG-CSF (produced by Chinese hamster ovary cells) were nearly equipotent in specific biologic activity. These results confirm the CPA-mouse assay as an especially useful assay method for quantifying the in vivo activity of hG-CSF.
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PMID:Quantitative in vivo assay of human granulocyte colony-stimulating factor using cyclophosphamide-induced neutropenic mice. 169 32

Stimulation of red cell production by erythropoietin and of granulocyte production by granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage-CSF (GM-CSF) has been demonstrated in several clinical studies. The first study to show that a human CSF could be used to shorten the period of neutropenia and reduce the risk of serious infection following intensive combination chemotherapy was carried out in Manchester using G-CSF. The period of neutropenia was significantly shortenened (by a median of 80%) and the neutrophil count levels were restored and above normal by 14 days after chemotherapy. In view of these results a further study was undertaken to examine the possibility of using intensive two weekly chemotherapy under cover of G-CSF. Treatment with Doxorubicin at doses of 75, 100, 125 and 150 mg/m2 was followed by infusion of G-CSF for 11 days. The neutrophil counts returned to normal within 12-14 days, allowing the delivery of up to three cycles of high dose chemotherapy at 14 day intervals. These studies demonstrated that intensive chemotherapy with dose-limiting myelodepression can be given with increased frequency under cover of G-CSF. Our studies using GM-CSF have also shown that administration by continuous i.v. infusion can reduce the period of life-threatening neutropenia following high dose Melphalan (120 mg/m2) without resort to autologous bone marrow transplantation (ABMT). In this study the period of granulocytopenia following Melphalan (less than 500 g x 10(9)/m2) was less than 15 days. This compares favourably with other series using high dose Melphalan followed by ABMT without CSF, where the duration of severe neutropenia was prolonged beyond three weeks. Although it appears that G-CSF and GM-CSF should be given either by continuous i.v. infusion or s.c. injection at doses between 3-10 micrograms/kg/day to obtain maximum biological effect, a great deal more work is required to determine optimum schedules and investigate the possibility of using more than one bioregulator.
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PMID:Growth factor-assisted chemotherapy--the Manchester experience. 169 Jun 24

The short biologic half-life of the peripheral neutrophil (PMN) requires an active granulopoietic response to replenish functional PMNs and to maintain a competent host defence in irradiated animals. Recombinant human G-CSF (rhG-CSF) was studied for its ability to modulate haemopoiesis in normal dogs as well as to decrease therapeutically the severity and duration of neutropenia in sublethally and lethally irradiated dogs. For the normal dog, subcutaneous administration of rhG-CSF induced neutrophilia within hours after the first injection; total PMNs continued to increase (with plateau phases) to mean peak values of 1000 per cent of baseline at the end of the treatment period (12-14 days). Bone-marrow-derived granulocyte-macrophage colony-forming cells (GM-CFC) increased significantly during treatment. For a sublethal 200 cGy dose, treatment with rhG-CSF for 14 consecutive days decreased the severity and shortened the duration of neutropenia and thrombocytopenia. The radiation-induced lethality of 60 per cent after a dose of 350 cGy was associated with marrow-derived GM-CFC survival of 1 per cent. Treatment with rhG-CSF markedly reduced the lethality associated with exposure to 350 cGy of radiation to zero. White blood cell (WBC) and platelet recovery kinetics were correlated with degree of marrow damage. The rhG-CSF reduced the severity and duration of neutropenia. Control animals required antibiotic therapy (WBC less than 1000 mm3) for a total of 16 days versus 3 days for rhG-CSF-treated dogs. The duration of thrombocytopenia was reduced, although the severity of depletion was unchanged with treatment. These data indicate that in the lethally irradiated dog, effective cytokine therapy with rhG-CSF will increase survival through the induction of earlier recovery of neutrophils and platelets.
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PMID:Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation. 169 Dec 55

A 55-year-old man was admitted to our hospital for the evaluation of neutropenia. On physical examination, he had apthae and splenomegaly. CBC showed 1,000/microliter WBC with 5% neutrophils, and microcytic anemia consistent with iron deficiency. Bone marrow examination revealed a marked decrease of mature neutrophils, but normal percentage of immature myeloid cells. There was no morphological abnormality in the hemopoietic cells. He had no drug or family history responsible for the neutropenia. Anti-neutrophil auto-antibody was negative. Hence, a diagnosis of chronic idiopathic neutropenia (CIN) was made. He developed frequent episodes of infection such as balanitis, peri-anal infection, gingivitis, and pharyngitis. He was treated with steroid pulse therapy, anabolic hormone, and high dose gamma-globulin infusion, but no significant improvement occurred. Then, recombinant granulocyte-colony stimulating factor (rG-CSF) was started. The neutrophil count was normalized by the 7th day of 5 micrograms/kg/day rG-CSF administration. The administration of G-CSF was discontinued after a 14-day course. Thereafter, the neutrophil count remained at near normal level (approximately 1,500/microliter) and there have been no episodes of infection in the last 5 months. However this cannot be explained simply by the direct effect of rG-CSF on the myeloid precursors; rather, it suggests some unknown effect of G-CSF on the bone marrow microenvironment regulating myeloid hemopoiesis. We consider this to be a rare case of CIN with frequent episodes of infection, which was successfully treated with G-CSF.
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PMID:[Chronic idiopathic neutropenia improved by recombinant granulocyte colony stimulating factor]. 169 94

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