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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The superoxide (O2-)-releasing capacity in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the priming effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on FMLP-induced O2- release were investigated in neutrophils from 14 patients with myelodysplastic syndromes (MDS). The O2(-)-releasing capacity in MDS neutrophils varied from patient to patient. As compared with normal neutrophils, the O2(-)-releasing capacity in MDS neutrophils was increased in 9/14 patients, normal in three patients and decreased in two patients. There was no close relationship between the O2(-)-releasing capacity and the peripheral blood neutrophil count or the plasma concentration of C-reactive protein. The priming of neutrophils by rhG-CSF was not observed in five patients, whereas rhGM-CSF primed neutrophils from all patients. The priming effect of rhGM-CSF was consistently greater than that of rhG-CSF in each patient. The intravenous administration of rhG-CSF (300 micrograms/body) to two MDS patients showed an increase in the peripheral blood neutrophil count and enhancement of neutrophil O2- release. These findings demonstrate that the neutrophil O2(-)-releasing capacity in MDS varies from patient to patient and is not always impaired, and that rhGM-CSF is able to prime neutrophils which never respond to rhG-CSF.
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PMID:Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on respiratory burst activity of neutrophils in patients with myelodysplastic syndromes. 767 62

A 6-year-old white male had a myelodysplastic syndrome (refractory anemia with excess blasts in transformation) and was treated with high dose chemotherapy. A combined esterase stain of the marrow blasts showed granulocytic differentiation. Subsequently, persistent pancytopenia with a severely hypocellular bone marrow developed, which was treated with a combination of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Sixteen days after the initiation of therapy, histologic examination of the bone marrow revealed a marked proliferation of histiocytes. To the best of the authors' knowledge, this is the first report of histiocytic proliferation in the bone marrow after colony-stimulating factor therapy.
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PMID:Bone marrow histiocytic proliferation in association with colony-stimulating factor therapy. 827 47

The hematopoietic growth factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been cloned, produced in bacteria and yeast, and approved for clinical use in the treatment of neutropenia. Both factors stimulate the proliferation and maturation of neutrophil progenitors and enhance the effector functions of mature cells by interaction with specific receptors on the cell surface. Serum levels of G-CSF correlate inversely with the neutrophil count, suggesting that G-CSF may be the normal homeostatic regulator of the neutrophil count, while GM-CSF is generally undetectable in the serum and appears under normal physiologic conditions to act locally at inflammatory sites. Phase I and II clinical trials with these factors demonstrated minimal toxicity for G-CSF and mild to moderate dose-dependent toxicity for GM-CSF. Recent clinical trials, including double-blind, randomized studies, support a role for these growth factors in the treatment of chronic neutropenias, such as Kostmann's syndrome, acquired immune deficiency syndrome (AIDS), aplastic anemia, and myelodysplasia, as well as in acute neutropenias, such as cyclic neutropenia, chemotherapy-induced neutropenia, and bone marrow transplantation.
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PMID:Southwestern Internal Medicine Conference: clinical use of hematopoietic growth factors. 768 52

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used extensively to restore hematopoietic system function after damage by diseases such as myelodysplastic syndrome or by cytotoxic anti-cancer agents used during cancer chemotherapy or prior to bone marrow transplantation. The clinical benefits of this approach have included fewer infections, fewer hospital days and less antibiotic use. In the future, the use of GM-CSF will be focused on special situations within these general areas, plus new directions that were not previously given sufficient attention. Examples of focused approaches include the use of GM-CSF in the control of fungal or protozoal disease and to take advantage of anti-tumor effects of myeloid cell activation. The anti-microbial effects will also be explored in patients who are not neutropenic but have serious infections which may be benefited by increased stimulation to myeloid cell function. The use will also be focused on mobilization of peripheral blood progenitor cells and in cycling of normal hematopoietic and malignant cells. The new directions will include use of GM-CSF by local application in healing of cutaneous ulcers, rapid wound closure and skin grafting. Because of its potent effects on immunologic mechanisms of antigen presentation, it will be used in several ways as a vaccine adjuvant. This adjuvant action will be directed at enhancing immunologic responses to antimicrobial antigens and anti-tumor antigens. The future of GM-CSF as a tool for hematopoietic and immunologic stimulation with resulting important clinical benefits is clear.
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PMID:Future uses of granulocyte-macrophage colony-stimulating factor (GM-CSF). 769 62

Treatment of myelodysplastic syndromes (MDS) with recombinant human erythropoietin (Epo) is successful in only 10% to 25% of patients. We performed a pilot study in 10 anaemic patients with MDS to examine whether sequentially applied recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and Epo improves haemoglobin levels and/or reduces red blood cell transfusion requirements. Morphological diagnoses of patients were refractory anaemia (RA) in 3 cases, RA with ring sideroblasts in 3 cases and RA with excess blasts in 4 cases. GM-CSF was given subcutaneously at a dose of 150 micrograms/m2/d during the initial 10 days. From day 11, Epo was administered by subcutaneous injections for 8 weeks at a dose of 100 U/kg/d and subsequently at an escalated dose of 200 U/kg/d in 3 patients. Changes in reticulocyte counts, haemoglobin levels, RBC support and ferrokinetic parameters were compared with pretreatment values. Two out of 8 evaluable patients showed a rise in haemoglobin levels at week 8 and 10, respectively, and lost their transfusion dependency for a period of 13 and 27 weeks. In 1 patient, haemoglobin level increased only after dose escalation of Epo (200 U/kg/d). Leukocyte counts remained uneffected by treatment with Epo, while 1 patient showed a 4-fold increase in platelet numbers. Toxicity was mild. Two patients died of pneumonia and global heart failure, respectively, unrelated to growth factor therapy. Based on this pilot study, we conclude that sequential treatment with GM-CSF and Epo does not increase erythroid responses in anaemic patients with MDS. Because of the delayed increase in haemoglobin in both responders, we surmise that the beneficial effects were induced by Epo alone.
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PMID:Sequential administration of recombinant human granulocyte-macrophage colony-stimulating factor and human erythropoietin for treatment of myelodysplastic syndromes. 785 74

The complication of secondary myelodysplastic syndrome (sMDS) during the course of multiple myeloma (MM) has been recognized for more than a decade. sMDS occurs years after MM diagnosis, and typically, at sMDS presentation the MM is stable or inactive. We report a 56-year-old patient, who developed sMDS 15 years following the diagnosis of IgG-lambda MM, which had been completely stable for 13 years. However, very soon after sMDS was diagnosed, the MM relapsed and required combination chemotherapy. The first cycle of vincristine, adriamycin and dexamethasone (VAD) resulted in severe neutropenia and sepsis, which was treated with antibiotics and recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Two weeks after GM-CSF administration a transformation to acute myeloblastic leukemia was observed. The relation between GM-CSF and the leukemic transformation is discussed and the possible contribution of the cytokine to the stimulation of this complication is emphasized.
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PMID:Is granulocyte-macrophage colony-stimulating factor (GM-CSF) safe in myelodysplastic syndromes? 789 Feb 61

Acute myeloid leukemia preceded by a myelodysplastic syndrome (MDS-AML) is generally regarded as a high-risk type of AML, where remissions are rare and of short duration. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is suggested to increase the sensitivity of leukemic cells to cycle-specific drugs. In this study 14 MDS-AML patients were given rhGM-CSF together with standard induction chemotherapy (TAD). rhGM-CSF was started 48 h prior to chemotherapy and given for up to 3 weeks. The results showed eight (58%) complete and two (14%) partial remissions, while another two (14%) patients had minor responses. One patient relapsed after 1 year, and then responded a second time. rhGM-CSF had to be stopped owing to local allergic reactions in two patients, both non-responders, but was otherwise well tolerated. Compared with our historical group of controls we found significantly higher remission rates, fewer early deaths, fewer fever days, and fewer days with both neutropenia and thrombocytopenia among the patients treated with rhGM-CSF and TAD. The estimated median over-all survival was 332 days. The severity of initial myelodysplastic changes did not correlate to the outcome of therapy but the degree of peripheral blood dysplasia decreased among responding patients. MDS-AML patients in this pilot study did respond better, and with minimal toxicity, when standard induction chemotherapy was given in combination with rhGM-CSF.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in acute myeloid leukemia evolving from myelodysplastic syndromes: a pilot study. 793 58

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor known to promote the proliferation and differentiation of precursors of granulocytes and monocytes. GM-CSF at standard doses (125-500 micrograms/m2) alleviates neutropenia secondary to cytotoxic chemotherapy, myelodysplastic syndromes, and aplastic anemia, but has minimal effect on anemia or thrombocytopenia. GM-CSF at doses < 30 micrograms/m2 has been reported to improve platelet counts in some patients exhibiting cytopenia related to hematologic disorders such as aplastic anemia and myelodysplastic syndrome. Low-dose GM-CSF (10-20 micrograms/m2) was evaluated in 20 patients with transfusion-dependent thrombocytopenia persisting after myeloablative cytotoxic chemotherapy or with disease-related cytopenia. Seven patients (35%) responded as defined by a reduction in the platelet transfusion requirements by at least 75%. Low-dose GM-CSF did not significantly increase neutrophil counts or decrease red blood cell transfusion requirements. These results indicate that low-dose GM-CSF has a thrombopoietic effect in about one-third of patients with platelet transfusion-dependent thrombocytopenia which has not been observed at higher doses.
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PMID:Effect of low-dose granulocyte-macrophage colony-stimulating factor (LD-GM-CSF) on platelet transfusion-dependent thrombocytopenia. 794 85

A novel long-term cultured myeloid cell line was established from the bone marrow of a patient with myelodysplastic syndrome (MDS). This cell line, designated MDS92, proliferated in the presence of interleukin-3 or granulocyte-macrophage colony-stimulating factor and transiently in the presence of Steel factor, with a tendency for gradual maturation, and formed myeloid colonies in the semi-solid culture condition. In addition, the MDS92 cell line represented rather complicated karyotypic abnormalities including the deletion of fifth and seventh chromosomes and a point mutation at codon 12 of the N-ras oncogene. These characteristics of the MDS92 cell line are exclusively compatible with the property of preleukaemia.
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PMID:Establishment and characterization of a novel myeloid cell line from the bone marrow of a patient with the myelodysplastic syndrome. 794 63

As phase II study, we treated 18 patients with myelodysplastic syndrome (MDS) and 37 patients with aplastic anemia (AA) with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 14-28 days. Administration of rhGM-CSF resulted in a dose-dependent increase in circulating granulocyte counts, which was statistically significant in patients with AA. There were no consistent changes in monocyte and lymphocyte counts. Although no increase in both thrombocyte and erythrocyte counts was detected in the majority of the patients, a response of both lineages to rhGM-CSF, in addition to granulocyte lineage, was observed in 3 patients. Drug-associated adverse events developed in 28 patients (51%). The most frequent adverse event was fever. In general, the treatment with rhGM-CSF was well tolerated. The results suggest that rhGM-CSF is effective for patients with MDS and AA.
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PMID:Phase II study of recombinant human granulocyte-macrophage colony-stimulating factor in myelodysplastic syndrome and aplastic anemia. 821 99


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