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

The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by refractory cytopenias in one or more myeloid cell lines and an increased probability of transformation to acute leukemia. Supportive care remains the mainstay of therapy in MDS and frequently includes monotherapy and combination therapy with hematopoietic growth factors, such as erythropoietin, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor. Clinical trials have demonstrated the ability of growth factors to improve neutropenia and anemia in selected patients with MDS, which may have clinical, quality-of-life, and economic benefits for patients even though overall survival has not been improved. This paper reviews the role of hematopoietic growth factors in the treatment of MDS.
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PMID:Hematopoietic growth factors in myelodysplastic syndromes. 1456 88

Neutropenia and anaemia are serious complications of myelosuppressive chemotherapy. They have a negative impact on patient quality of life and may reduce response to treatment. Febrile neutropenia, a potentially life-threatening complication of neutropenia, frequently requires hospital admission, while fatigue and weakness from anaemia reduce patient's capacity for activity. Pegfilgrastim and darbepoetin alfa, were designed to simplify and optimise treatment for patients with cancer. Once-per-cycle pegfilgrastim is as effective as daily filgrastim with respect to duration of severe neutropenia (DSN) and may have a lower incidence of febrile neutropenia than filgrastim. Darbepoetin alfa has enhanced biological activity and a serum terminal half-life three-fold longer than that of erythropoietin (EPO), which translates into rapid and sustained correction of anaemia with less frequent dosing. These novel cytokines have the potential to simplify the management of neutropenia and anaemia with fewer injections and less disruption to patients daily lives.
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PMID:Optimising management of neutropenia and anaemia in cancer chemotherapy-advances in cytokine therapy. 1456 20

T-cell large granular lymphocytic lymphoproliferative disease (T-LGL) is often associated with life-threatening cytopenias. Twenty-five subjects with anaemia and/or neutropenia caused by T-LGL were treated with cyclosporin A (CSA) 5-10 mg/kg/d for at least 3 months. Eighteen patients survived between 35 and 77 months after starting treatment. Fourteen patients [56%; 95% confidence interval (CI) 35-76%] responded to CSA with sustained improvement in the neutrophil count or transfusion independence. Seven had complete normalization of blood counts, and four achieved a durable response only after the addition of erythropoietin. Sustained response required continued low-dose CSA. In a multivariate analysis, HLA-DR4 was highly predictive of CSA responsiveness (odds ratio 18; 95% CI 1.8-184). T-LGL subtype, LGL counts after therapy, lymphocytic marrow infiltration and bone marrow cellularity did not significantly affect the probability of response. We conclude that CSA is effective in inducing haematological responses in HLA-DR4-positive patients and that T-LGL is likely to have an immune pathogenesis.
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PMID:HLA-DR4 predicts haematological response to cyclosporine in T-large granular lymphocyte lymphoproliferative disorders. 1461 4

Neutropenia and anemia are important complications of cancer chemotherapy and can be prevented and treated with granulocyte colony-stimulating factor and erythropoietin.
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PMID:The benefits of haematopoietic growth factors in the management of gynaecological oncology. 1503 69

F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) is used extensively in oncology to diagnose, stage, and restage patients with various malignancies. Many patients treated for malignancies develop neutropenia secondary to marrow suppressive chemotherapy and are subsequently treated with synthetic hematopoietic growth factors (HGF), both granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF). Patients taking HGF can present a diagnostic challenge for those interpreting PET because they can demonstrate diffuse marrow uptake on FDG-PET scans, mimicking diffuse bone marrow metastases. It has not been reported whether bone marrow uptake is affected on PET scans in patients taking erythropoietin, the erythroid-specific cell-line stimulator. We report a case of extensive diffuse bone marrow uptake in a 77-year-old man with a history of colon cancer who began taking erythropoietin 3 weeks before his PET scan. This case demonstrates the need to consider erythropoietin in the differential diagnosis of possible etiologies causing diffuse bone marrow uptake on PET scans.
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PMID:Diffuse bone marrow uptake on whole-body F-18 fluorodeoxyglucose positron emission tomography in a patient taking recombinant erythropoietin. 1516 84

Hepatitis C (HCV) contributes significantly to the morbidity and mortality of patients coinfected with human immunodeficiency virus (HIV) and those with recurrent hepatitis C after successful liver transplantation. Treatment of hepatitis C in these patient populations, while crucial, can be quite challenging. Baseline cytopenias, in particular, may limit dosing of interferon and/or ribavirin or preclude therapy entirely when standard guidelines are followed. Concomitant medications, opportunistic infections, and other bone marrow insults account for the anemia, neutropenia, and thrombocytopenia frequently encountered in these patients. Sustained virologic response rates in published series for HIV/HCV and post-transplantation HCV have not reached those seen in treatment of HCV alone, despite the highly selected patient populations chosen for these studies. Hematopoietic growth factors such as erythropoietin and granulocyte-colony stimulating factors may be used to improve the anemia and neutropenia seen during treatment of HCV. Reported experience with these growth factors is limited in HIV/HCV coinfected patients, but studies are underway to determine if growth factors improve adherence to therapy and perhaps virologic response rates. Post-transplantation studies of HCV therapy have reported more liberal use of growth factors; however, discontinuation rates have been high and virologic response rates have been disappointing. Further study of growth factors as a means to increase sustained virologic response rates and maintain adequate dosing and duration of interferon and ribavirin therapy in these patient populations is needed.
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PMID:Role of growth factors in the treatment of patients with HIV/HCV coinfection and patients with recurrent hepatitis C following liver transplantation. 1559 23

Pegylated (PEG)-interferon and ribavirin combination therapy are the standard of care for the treatment of chronic hepatitis C and are associated with a high rate of sustained virologic response. However, there is a high incidence of hematologic side effects with this therapeutic regimen. Hematologic side effects are particularly common; bone marrow suppression caused by interferon may result in neutropenia and thrombocytopenia. Ribavirin is directly toxic to red blood cells and is associated with hemolysis, which is usually dose-related but self-limited. Historically, the traditional management of hematologic side effects of interferon therapy has been dose reduction. However, recent studies have shown that response to therapy is strongly influenced by adherence to optimal doses of interferon and particularly ribavirin. Therefore, there is increasing emphasis on the use of growth factors such as filgrastim and erythropoietin to stimulate bone marrow production of erythrocytes and leukocytes to allow patients to receive the optimal doses of interferon and ribavirin. The incidence, magnitude, and possible mechanisms of hematologic complications associated with interferon and ribavirin are described in this review.
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PMID:Hematologic side effects of interferon and ribavirin therapy. 1559 25

Many leukemia and cancer cells exhibit constitutive activation of STAT5, which was suggested to provide an anti-apoptotic advantage. Transformation of cytokine-dependent hematopoietic cells, such as Ba/F3 cells to autonomous growth and tumorigenicity equally results in selection for constitutive activation of STAT5. We compared STAT5 signaling between erythropoietin(Epo)-dependent cells and cells that were transformed by oncogenic activation of the erythropoietin receptor (EpoR) by coexpression of the gp55-P envelope protein of the spleen focus forming virus or by expression of the R129C constitutively active EpoR mutant. In transformed cells it was mainly STAT5B that was constitutively activated. In contrast, Epo stimulation activated both STAT5A and STAT5B. In transformed cells, chromatin immunoprecipitation (ChIP) showed STAT5 to be physically bound to promoters of STAT5 target genes, such as Bcl(XL), and to be able to promote transactivation of the Bcl(XL) promoter in a constitutive fashion. Sequencing of native sequences after ChIP with anti-STAT5 antibodies in Epo-dependent and -transformed cells indicated that in gp55-transformed cells, STAT5B bound in the chromatin not only to N3 high affinity, but also to low affinity N4 GAS sites. Transactivation for N3 GAS sites in luciferase reporters was specific to gp55 transformation. Because we also found preferential constitutive STAT5B activation after transformation of cells by a truncated form of the G-CSF-R that produces severe neutropenia (Kostmann syndrome) and favors leukemia in humans, we discuss the potential role of STAT5B in oncogenic transformation of hematopoietic cells.
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PMID:Differential STAT5 signaling by ligand-dependent and constitutively active cytokine receptors. 1567 77

Recombinant human erythropoietin (r-EPO) has been used in Myelodysplastic Syndrome (MDS) patients with anaemia since the early nineties. In low-risk MDS patients, other haemopoietic growth factors (HGFs) (granulocyte-colony stimulating factor, G-CSF, granulocyte-macrophage-colony stimulating factor, GM-CSF, and interleukin 3, IL-3) have been used to synergise the effects of r-EPO on erythroid growth and to increase neutrophil count in patients with severe neutropenia. In high-risk MDS, or in patients with post-MDS AML, myeloid HGFs have been used to push blasts into the S-phase, thus increasing their sensitivity to antiblastic drugs. Several trials have shown that r-EPO can increase haemoglobin levels and improve QoL in patients with anaemia associated to MDS. The selection of patients with a high probability of response to HGFs is based on the careful consideration of several clinical and biological parameters, i.e., among others, basal EPO and transfusional needs, disease duration, FAB or WHO subtypes, and IPSS score. Treatment of anaemic MDS patients with HGFs should become "patient oriented" and different types, schedules, and duration of treatment have to be designed according to the specific criteria which most likely predict, for each individual patient, the best chance of responding favourably to therapy.
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PMID:Haemopoietic growth factors in myelodysplastic syndromes: towards patient-oriented therapy? 1594 26

In spite of recent advances in the treatment of myelodysplastic syndromes (MDS), supportive care remains a very important part of the therapy. Red blood cells transfusions are the most important component of this supportive care. They transiently relieve anemia symptoms and alleviate their effects on quality of life and daily functioning. Platelet transfusion therapy is less frequently needed, at least in low-risk MDS. Dealing with an increased risk of infections linked to neutropenia, mainly by broad spectrum antibiotics, is also needed, more often in advanced stages of [dict: MDS] or when the MDS evolves to acute myeloid leukemia. Chronic red blood cell transfusions expose patients to various side-effects, including blood components intolerance reactions and alloimmunization risks, but also increased frequency of iron overload, a more significant problem in low-risk heavily transfused MDS patients, who have prolonged life expectancy. The use of growth factors is becoming a more and more important part of current supportive care. High-dose erythropoietin is able to reduce or suppress red blood cell transfusions needs in selected subgroups of MDS. The short-term use of granulocyte colony-stimulating factor is also often proposed in infections, although not formally established by prospective trials. Although trials of growth factors with thrombopoeitic activity have been performed with interleukin 11 and are underway with thrombopoeitin, none of them are available for routine use.
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PMID:Supportive care including growth factors in myelodysplastic syndromes. 1602 1


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