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

Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by neutropenic episodes at 14-day intervals. The biochemical basis for CH is not known but may involve a regulatory defect of the response to or production of a hematopoietic growth factor. Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to two CH and one normal dog caused a marked leukocytosis (greater than 50,000 WBCs) in all three dogs. The leukocytosis was due largely to a greater than tenfold increase in neutrophils. Less pronounced but significant elevations in monocytes occurred during G-CSF treatment. The elevated WBC count was maintained for more than 20 days in all three dogs, and two predicted neutropenic episodes were prevented in both CH dogs during rhG-CSF treatment. A decline in the WBC count occurred simultaneously in all three dogs during the last five treatment days and was presumably associated with the development of neutralizing antibodies to the heterologous rhG-CSF protein. Bone marrow evaluation indicated that the swings in the myeloid/erythroid progenitor cells that are characteristic of CH were eliminated by rhG-CSF treatment in both CH dogs. These results suggest that the regulatory defect in canine CH can be temporarily alleviated by treatment with rhG-CSF and point to the potential treatment of human cyclic neutropenia with this agent.
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PMID:Correction of canine cyclic hematopoiesis with recombinant human granulocyte colony-stimulating factor. 245 81

Hematopoietic growth factors comprise a family of hematopoietic regulators with biologic specificities defined by their ability to support proliferation and differentiation of blood cells of different lineages. The biologic specificities of these factors are highly complex, dose dependent, and frequently overlapping. Recent advances in the cloning of hematopoietic growth factor genes and the availability of recombinant material have led investigators to conduct clinical trials with these agents. Some of these factors have been studied and used in chemotherapy-induced neutropenia, myelodysplastic syndromes, and bone marrow failure syndromes. In this paper, we review the experience with growth factors that have been tested and that currently are being introduced in clinical trials. In addition, we report some factors with possible future interest for clinicians and researchers.
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PMID:Clinical use of recombinant human hematopoietic growth factors. 267 57

Recombinant granulocyte colony-stimulating factor (rHuG-CSF) is a hematopoietic growth factor that acts selectively on the neutrophil lineage, and has had a major impact on clinical practice. Two forms are in clinical use: filgrastim has been approved for use in more than 45 countries for the amelioration of chemotherapy-induced neutropenia and restoration of granulopoiesis following bone-marrow transplantation and lenograstim has been approved in Europe and Japan. In some countries, rHuG-CSF is also approved for various other indications, such as severe chronic neutropenia. Infection and neutropenia are a major cause of morbidity and mortality following cytotoxic chemotherapy, and there is a known correlation between neutropenia and the risk of infection. Hematopoietic growth factors have been used successfully in the prevention and treatment of neutropenia. There is evidence to suggest that use of rHuG-CSF before the onset of neutropenia allows patients to receive the maximum benefit; however, patients who do not receive rHuG-CSF prophylactically still benefit from the use of rHuG-CSF for the treatment of febrile neutropenia. These patients have an accelerated neutrophil recovery and a shorter duration of febrile neutropenia. These effects seem to translate into a significant reduction in the number of patients requiring prolonged hospitalization. This paper reviews the use of rHuG-CSF in the treatment of febrile neutropenia and describes how it is routinely used by hematologists and oncologists in non-clinical trial settings.
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PMID:The clinical utility of granulocyte colony-stimulating factor: early achievements and future promise. 753 47

The ifosfamide/carboplatin/etoposide (ICE) combination represents an active chemotherapy regimen across a wide variety of disease types. The most common limiting toxicity for all three of these agents individually and in combination is myelosuppression. Thus, this regimen represents an ideal model to evaluate the role of hematopoietic growth factor support in amelioration of hematologic toxicity, maintenance of dose intensity, and dose escalation. While chemotherapy strategies using colony-stimulating factors have abrogated neutropenia, cumulative thrombocytopenia is common with many chemotherapy regimens, including ICE chemotherapy. In preclinical and phase II trials, monotherapy with recombinant human interleukin-6 (IL-6) has demonstrated substantial thrombopoietic activity, but with little enhancement of neutrophil recovery. Thus, this study was designed to evaluate combination cytokine therapy with both recombinant IL-6 and granulocyte colony-stimulating factor (G-CSF) after ICE chemotherapy. Previously untreated patients with inoperable non-small cell lung cancer are eligible. Treatment includes two monthly cycles of ifosfamide 2,000 mg/m2 with mesna 1,600 mg/m2 intravenously on days 1, 2, and 3, carboplatin 350 mg/m2 intravenously on day 1 only, and etoposide 75 mg/m2 intravenously on days 1, 2, and 3. All patients then receive G-CSF at a dose of 5 micrograms/kg/d subcutaneously beginning on day 4 until a postnadir absolute neutrophil count of more than 10 x 10(9)/L. Cohorts of patients (n = 15) are randomized to receive 0, 1, 2.5, or 5 micrograms/kg/d of IL-6 subcutaneously on days 4 to 13 in successive cohorts. This study has now reached its target accrual in all cohorts. The final data analysis is in progress. It is hoped that this trial will define the safety and tolerability of the simultaneous administration of IL-6 and G-CSF following ICE chemotherapy in patients with non-small cell lung cancer. In addition, this trial should determine the biologic activity and hematopoietic recovery observed during the simultaneous administration of these two cytokines in this setting.
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PMID:The role of hematopoietic growth factors in support of ifosfamide/carboplatin/etoposide chemotherapy. 754 16

We have previously demonstrated an inverse relationship between circulating endogenous G-CSF levels and myeloid engraftment post-BMT. A new early-acting hematopoietic growth factor, Steel factor (SLF), has recently been demonstrated to induce the proliferation of early hematopoietic progenitor cells and synergistically stimulate committed progenitor cells in the presence of lineage-specific CSFs. In this pilot study, we determined the temporal relationship between endogenous SLF levels and the circulating absolute neutrophil count (ANC) (myeloid engraftment) in both children and adults undergoing both allogeneic and autologous BMT. Pre-BMT SLF levels were 2600 +/- 100 pg/ml compared to significantly lower levels of G-CSF (30-50 pg/ml). The circulating SLF level was significantly decreased throughout the post-BMT period (ANC < or = 200 x 10(6)/l: 1500 +/- 600 pg/ml; ANC 200-500 x 10(6)/l: 1780 +/- 130 pg/ml; ANC > or = 500 x 10(6)/l: 1690 +/- 110 pg/ml) (p < 0.001). There was a lack of an inverse relationship between the circulating SLF level and the ANC (r = -0.43) (p = NS). For comparison, SLF levels from immune thrombocytopenia (platelet < = or 20 x 10(9)/l) and chemotherapy-induced neutropenia patients (ANC < or = 200 x 10(6)/l) were similar to pre-BMT levels but significantly higher than post-BMT levels (p < or = 0.02 and < or = 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased endogenous circulating Steel factor (SLF) levels following allogeneic and autologous BMT: lack of an inverse correlation with post-BMT myeloid engraftment. 767 98

The authors describe the development of a clinical protocol to treat mustard gas-induced myelosuppression with granulocyte colony stimulating factor (G-CSF), a hematopoietic growth factor. Limited clinical evidence suggests a significant role for mustard gas-induced myelosuppression in the overall morbidity of mustard gas victims. Initial data from primates revealed that G-CSF could ameliorate neutropenia following nitrogen mustard exposure. Exploiting the extensive oncologic experience with G-CSF, which demonstrated its safety and absence of serious side effects the authors developed a clinical protocol for use of this drug in potential mustard gas victims in the Persian Gulf conflict.
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PMID:Granulocyte colony stimulating factor (G-CSF) for mustard-induced bone marrow suppression. 768 84

Recombinant granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor used for the reduction or prevention of cyclic neutropenia in cancer patients. Neutropenia is a major factor contributing to infection, morbidity, and mortality. Neutropenia also reduces the dosage of cytotoxic agents and often interrupts the course of treatment. The recent development of cloning G-CSF has been a major advancement in treating cyclic neutropenia. This article focuses on the mechanism of action, pharmacokinetics, and the clinical applications of G-CSF.
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PMID:Recombinant human granulocyte colony-stimulating factor: an overview. 769 25

The present study was designed to determine whether Filgrastim, a neutrophil-specific hematopoietic growth factor, could be administered simultaneously with intensive induction chemotherapy for adult acute lymphoblastic leukemia (ALL). The effect of Filgrastim on the severity of chemotherapy-induced neutropenia, fever, and infections was assessed in 15 patients treated according to the protocol of the German multicenter ALL (GMALL) trial 04/89. Filgrastim (5 micrograms/kg/day) was given concurrently with successive cycles of cyclophosphamide, cytosine-arabinoside (ara-C), 6-mercaptopurine (6MP), prednisone (PRD), intrathecal methotrexate, and prophylactic cranial irradiation. During the study period the median total duration of severe neutropenia (< 0.5 x 10(9)/l) in 13 evaluable patients was 8 days, individual periods of neutropenia typically were short. Infections occurred in six patients; seven patients remained fever-free during treatment with Filgrastim. We conclude that simultaneous treatment with Filgrastim and chemotherapy in this specific setting is feasible and well tolerated. The efficacy of this treatment approach in terms of overall treatment results requires further testing in a randomized trial.
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PMID:Simultaneous administration of granulocyte colony-stimulating factor (Filgrastim) and induction chemotherapy in acute lymphoblastic leukemia. A pilot study. 769 82

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

The possibility of predicting the clinical effects of cytokines from in vitro data is discussed, using GM-CSF as an example. GM-CSF incubated with bone marrow cells has been shown to induce proliferation and colony formation, predominantly of the colony-forming unit granulocyte and granulocyte-macrophage types. Daily treatment of normal monkeys with GM-CSF resulted in transient neutropenia followed by neutrophilia. After withdrawal of GM-CSF the neutrophil levels returned to baseline. Predictably, GM-CSF administration results in accelerated neutrophil recovery in patients with chemotherapy-induced neutropenia. GM-CSF has also been shown to induce microbial killing by neutrophils and monocytes in vitro. This activity translated into a dose-related protection of GM-CSF-pretreated mice infected with lethal doses of micro-organisms. Interleukin-3 (IL-3) increases the cellularity of the bone marrow and GM-CSF can induce mobilization of bone marrow cells into the peripheral blood. Therefore, it was predicted and subsequently proved that a combination of these cytokines is synergistic, increasing the yields of peripheral blood progenitor cells which could be collected and then retransplanted into patients undergoing myeloablative chemotherapy. Monkeys injected with recombinant human IL-3 and GM-CSF had increased antibody titres to human IL-3 compared with monkeys given IL-3 alone, suggesting a potential use of GM-CSF which was not predicted from its in vitro results, that of vaccine adjuvancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prediction of the role of granulocyte-macrophage colony-stimulating factor in animals and man from in vitro results. 787 54


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