Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 31-year-old woman presented with fever and arthralgia. Despite treatment with antimicrobials and corticosteroids, her symptoms persisted. A diagnosis of myelodysplastic syndrome (MDS)-refractory anemia (RA) was made by pancytopenia, dysplasia, and trisomy 8. Cultures of bone marrow, blood, and gastric juice showed Mycobacterium avium-intracellulare (MAI). She was treated with antimycobacterial drugs and recombinant human G-CSF/M-CSF and showed an initial response, but spike fever recurred and pancytopenia progressed. Hepatosplenomegaly and marked retroperitoneal lymphadenopathy were revealed, indicating further dissemination of MAI. Treatment with recombinant human GM-CSF and very-low-dose cytosine arabinoside, was started but was not effective. This case showed significant reduction in peripheral blood T-lymphocytes, especially the CD4+ population, and low immunoglobulin levels. Immunodeficiency state associated with long-term steroid therapy and MDS seemed to contribute to the development of the disseminated infection with MAI.
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PMID:Disseminated Mycobacterium avium-intracellulare infection in a patient with myelodysplastic syndrome (refractory anemia). 817 3

The introduction of hematopoietic cytokines into the clinic has been rapid with three currently approved by the Food and Drug Administration and perhaps a dozen more in clinical trials. Combinations of cytokines have been relatively unexplored in the clinics. Knowledge about the use of cytokines with chemotherapy has grown considerably in the past few years. The literature relating to use of cytokines in support of standard chemotherapy, marrow failure syndromes associated with malignant disease, and dose intensification not requiring progenitor cell replacement has been reviewed. This review does not address the use of cytokines to support bone marrow transplantation and collection of progenitor cells. Hematopoietic cytokines shorten the duration of cytopenia and decrease infectious complications when used to support standard chemotherapy regimens. However, several randomized trials have failed to show a benefit of such cytokine-supported treatment programs in terms of antitumor response, palliation, or survival. One exception is granulocyte-macrophage colony stimulating factor used with aggressive but standard chemotherapy for high-risk non-Hodgkin lymphoma. Cytokines decrease the infectious complications of myelodysplastic syndromes and may decrease transfusion requirements. Marked escalations in chemotherapy doses are possible with specific chemotherapy regimens. These increase complete remission rates although no benefit in survival or palliation has yet been proven. Cytokines have not been effective in allowing escalation of doses with certain chemotherapy agents and regimens. Cytokines decrease hematopoietic toxicity with standard or escalated chemotherapy doses. Randomized trials are now beginning to define the true patient benefit of this capability.
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PMID:Hematopoietic cytokines. Current use in cancer therapy. 824 71

When purified control neutrophils were primed with GM-CSF, a significant increase in FMLP-induced MPO release was observed (mean +/- S.E.M., 3.4 +/- 0.8 mU/10(7) unprimed cells compared to 6.5 +/- 1.1 mU/10(7) primed cells, p < 0.001). This MPO release was greatly augmented by Cytochalasin B (Cy B), but after the addition of Cy B the priming effects of GM-CSF became less obvious. Exposure to GM-CSF without FMLP did not enhance MPO release. Within whole blood, FMLP produced negligible MPO release, but priming with GM-CSF prior to FMLP always resulted in a significant increase in MPO release. Myelodysplastic neutrophils released similar amounts of MPO in response to FMLP, compared with control cells (3.4 +/- 0.8 mU/10(7) control cells compared to 2.7 +/- 0.3 mU/10(7) MDS cells, p > 0.05). Priming with GM-CSF produced an increase in FMLP-stimulated MPO release comparable with control cells. In terms of total MPO content, although some MDS patients exhibited low levels, as a group there was no significant difference from controls (169 +/- 21 mU/10(7) control cells compared with 157 +/- 19 mU/10(7) MDS cells). These findings suggest that MPO activity is not a universal defect in MDS and cannot account for the defects in respiratory burst activity in these neutrophils.
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PMID:The effects of GM-CSF on myeloperoxidase release in normal and myelodysplastic neutrophils. 824 7

In a randomized phase II study, patients with myelodysplastic syndromes (MDS) with 10-30% blasts in the bone marrow and hematopoietic failure were treated with low-dose Ara C (2 x 10 mg/m2 subcutaneously (s.c.) days 1-14) and rhGM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day s.c.) given either following Ara C (days 15-21) or simultaneously (days 8-14) for 1-5 cycles. 108 patients with a median age of 65 years, range 17-80 years and refractory anemia with an excess of blasts (RAEB, n = 54), RAEB with transformation (RAEBt, n = 50) or with chronic myelomonocytic leukemia (CMML, n = 4) were evaluable. Complete remission was achieved in 15 cases (14%), 11 had a partial response (10%), and 16 a minor response (15%). Stable disease was reached in 35 cases (32%). There were 16 cases of toxic death (15%), progression occurred in 15 patients (14%). No differences existed between the two treatment arms with respect to response and duration of response. Prognostic factors for poor response included the presence of cytogenetic abnormalities and a history of previous blood transfusions. Major adverse events during treatment were hemorrhage (55%), infections (54%), and fever associated with GM-CSF administration (40%). The overall response rate ws 39%, median duration was 12.5 months from start of treatment which allowed responding patients to lead good quality life without further therapy. The question whether the combination is indeed superior to LD-Ara C alone is not settled but will be evaluated in an ongoing clinical trial.
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PMID:A randomized phase II study of low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in myelodysplastic syndromes (MDS) with a high risk of developing leukemia. EORTC Leukemia Cooperative Group. 828 81

We administered granulocyte-macrophage colony stimulating factor (GM-CSF) to patients with aplastic anemia and myelodysplastic syndrome (MDS), as a phase III trial. The GM-CSF was given by 3 hrs intravenous drip infusion daily for at least fourteen days. Twenty-five patients with aplastic anemia and nineteen patients with MDS were evaluable for efficacy. Peripheral blood granulocyte counts, especially neutrophil counts and eosinophil counts, increased markedly by the administration of GM-CSF in each disease. Fifteen patients with MDS and nineteen patients with aplastic anemia responded to the GM-CSF. Dose-related increase of granulocytes were seen in patients with MDS, but no relation was seen in patients with aplastic anemia. Adverse effects were observed in some patients and flu-like syndrome including fever, general fatigue and anorexia were seen most commonly but were transient. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in patients with aplastic anemia and MDS.
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PMID:[Clinical study of GM-CSF in patients with aplastic anemia and myelodysplastic syndrome. (CSF39-300 Study Group)]. 829 27

Recent progress of molecular biology and gene technology has developed a novel approach of clinical treatment. Several recombinant cytokines are already applied to clinical field. In this symposium, I introduced clinical application of some cytokines including GM-CSF, interleukin (IL)-1 and IL-3. The clinical benefits of IL-1 are; 1) IL-1 has an anti-tumor effect especially on cutaneous lymphoma and brain tumors, and 2) IL-1 has a function as hematopoietic growth factor for very immature hematopoietic stem cells. In the clinical Phase I/II study, IL-1 has been shown to have anti-tumor effect on cutaneous T-lymphoma via immune mechanisms. The side effects of IL-1 were variable including fever, fatigue, skin redness and so on, but they were all tolerable. The clinical phase studies of GM-CSF and IL-3 are now on going. The preliminary studies show that GM-CSF has granulo-poietic activity but not thrombo-poietic activity, and that IL-3 has multi-hematopoietic activity. These cytokines may be useful for treatment of disorders of hematopoietic stem cells such as aplastic anemia and myelodysplastic syndrome. The side effects of both cytokines are resemble, but all are tolerable.
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PMID:[Clinical application of new cytokines]. 835 Apr 99

To evaluate its clinical efficacy as well as its biologic safety, human recombinant Erythropoietin (rh-Epo) was given to 19 patients with myelodysplastic syndromes (MDS) in an open non-randomized study. Among the seventeen evaluable patients only two showed an apparent hematologic response to rh-Epo treatment. In these patients hemoglobin levels increased from a mean pretreatment value of 8.5 and 8.4 g/dl up to 11.7 and 11.3 g/dl respectively and remained relatively stable for several weeks. In one of these patients the transfusion requirement decreased from 4 to 1.5 units per month whereas the other had no transfusion requirement during the whole period of rh-Epo treatment. Interestingly, when the responding patients, after a "wash-out" period of at least ten weeks, received an additional course of rh-Epo results were less impressive. Before treatment the serum level of endogenous Epo was 18 and 110 mU/ml in the two responding patients, whereas a mean value of 532 mU/ml (range 17-2797 mU/ml) was observed in non responders. The treatment of MDS patients with rh-Epo was clinically well tolerated since no relevant side effects were registered. Moreover, no evidence of harmful cytogenetic changes nor activation of myeloid growth factor genes, as determined by Northern blot analysis of GM-CSF and G-CSF gene expression, could be related to rh-Epo treatment. Overall, it appears that administration of rh-Epo is well tolerated but the therapeutic effects appear to be restricted to a minority of patients and a limited period of time.
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PMID:Clinical and biological effects of erythropoietin treatment of myelodysplastic syndrome. 837 20

Prognosis in myelodysplastic syndrome (MDS) is not only correlated closely with blast cell count in bone marrow and chromosomal abnormalities but also correlated with decreased leucocyte count and function leading to acquisition of lethal infections. Recently, clinical trials in MDS have focused on the application of haemopoietic growth factors such as G-CSF or GM-CSF, which have proven to increase neutrophil count and function. However, these cytokines carry the risk of stimulating the malignant clone, particularly in patients with increased blast cell count. Therefore, investigation of cytokines which are able to stimulate neutrophil function without the potential risk of stimulating haemopoietic progenitor cells may be relevant for MDS. As the stimulatory effect of interleukin-8 on neutrophil function is well known, we investigated whether recombinant human IL-8 is also able to improve the function of neutrophils gained from patients with MDS. Using three different techniques--the E. coli killing assay (8 patients), the production of reactive oxygen as determined by cytochrome c reduction (7 patients) and chemiluminescence (8 patients)--a significant stimulation of neutrophil function at a concentration of 10 nm IL-8 was found in all test systems. No correlation with FAB classification was evident. On the other hand, IL-8 only mildly stimulated growth of myeloid progenitor cells in bone marrow culture of healthy individuals and MDS patients. This minimal stimulation was blocked by a neutralizing antibody directed against GM-CSF, suggesting an indirect effect of IL-8 via secondary GM-CSF release. Thus, IL-8 is able in vitro to repair the functional abnormalities of neutrophils from patients with MDS but has only a marginal influence on myeloid progenitor cells.
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PMID:Recombinant human interleukin-8 restores function in neutrophils from patients with myelodysplastic syndromes without stimulating myeloid progenitor cells. 838 40

Myelodysplastic syndrome is a frustrating disorder, which until recently lacked effective treatment. Patients usually succumb to infection, bleeding complications, or progression to acute leukemia. Recombinant cytokines such as granulocyte macrophage-colony stimulating factor, granulocyte-colony stimulating factor, interleukin-3, and erythropoietin have been used to ameliorate the cytopenias associated with this disease. Small clinical trials in myelodysplastic syndrome patients, using cytokines with myeloid activity (G-CSF, GMCSF, IL-3), have shown consistent elevations in the white blood cell counts with little success in elevating hemoglobin or platelets. Erythropoietin is able to increase the hemoglobin in a small group of myelodysplastic syndrome patients. Future trials using combinations of these cytokines may lead to multilineage effects.
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PMID:Will cytokines alter the treatment of myelodysplastic syndrome? 842 96

One of the most frequent cytogenetic abnormalities in human leukemia and myelodysplasia is an interstitial deletion within chromosome 5q. A tumor suppressor gene has been hypothesized to lie in 5q31, the smallest commonly deleted region. IRF-1, a gene whose product manifests anti-oncogenic activity, was mapped to 5q31.1. IRF-1 lies between IL-5 and CDC25C and is centromeric to IL-3 and GM-CSF. Among these genes, only IRF-1 was consistently deleted at one or both alleles in 13 cases of leukemia or myelodysplasia with aberrations of 5q31. Inactivating rearrangements of one IRF-1 allele, accompanied by deletion of the second allele, were also identified in one case of acute leukemia. Thus, IRF-1 may be a critically deleted gene in human leukemia and myelodysplasia.
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PMID:Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia. 843 56


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