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)

Subcutaneous administration of recombinant human Interleukin-1 beta (IL-1 beta) in a dose of 1-3 x 10(4) U/day for 14 to 72 days resulted in an increase in circulating granulocytes and bone marrow monocytes in all the 4 patients examined. Circulating platelet count was also increased in two of four patients with myelodysplastic syndrome (MDS) and aplastic anemia (AA). Bone marrow examination revealed an increase in megakaryocyte count in these patients, whereas the percentage of blast was not changed. An increase in blood platelet count was accompanied by an increase in serum GM-CSF in a patient with AA, whereas serum IL-6 level was not changed throughout the treatment with IL-1 beta. These findings suggest that IL-1 beta may be useful for the treatment of a proportion of patients with MDS and AA who are associated with thrombocytopenia.
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PMID:[Effect of subcutaneous administration of interleukin-1 beta on blood platelet count and serum GM-CSF in patients with myelodysplastic syndrome and aplastic anemia]. 143 38

Human urinary macrophage colony-stimulating factor (hM-CSF) is a glycoprotein with a molecular weight of 85 kDa which consists of two homologous subunits with a molecular weight of 43 kDa. It stimulates monocyte production through the stimulation of progenitor cells to differentiate to mature monocytes as well as neutrophil production through the stimulation of mature monocytes to produce granulocyte-macrophage and granulocyte CSF. It also enhances platelet production through the production of megakaryocyte potentiator (Meg-POT). Recently, proteoglycan type M-CSF has been found by our group. This type of M-CSF has a molecular weight of greater than 200 kDa and consists of a 43 kDa subunit and a 150-200 kDa subunit, the latter of which contains chondroitin sulfate glycosaminoglycan. This proteoglycan type M-CSF binds to extra-cellular matrix at the part of glycosaminoglycan. In addition to hematopoiesis-stimulating activity, M-CSF has a promoting activity on monocyte tumor-killing, osteoclast production and differentiation of cytotrophoblasts to syncytiotrophoblasts which secrete gonadotropin. M-CSF receptor (M-CSF-R) was found as a product of proto-oncogene, c-fms which consists of 972 amino acids. Mutations at Tyr 969 and Ser 301 of M-CSF-R has been found in patients with myelodysplastic syndrome and monocytic leukemia.
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PMID:[Function,molecular structure and gene expression of macrophage colony-stimulating factor]. 143 77

In a phase II study, 21 patients with MDS (RAEB, RAEBt, CMML and RA and RAS with severe cytopenia) were randomized to be treated with 3 courses of GM-CSF (3 micrograms/kg/day s.c.) alone (11 patients) or in combination with AraC (20 mg/m2/d s.c.) (10 patients) for 14-d periods, interrupted by 14-d rest periods. Eight patients discontinued the treatment. In the GM-CSF group a marked increase in WBC and neutrophil counts during each course of treatment administration were seen in most patients. Platelet counts decreased in 14 of 24 courses of treatment in the GM-CSF plus AraC group but in none of the GM-CSF group. Although the changes in the circulating blood cells were transient and the counts tended to return to the pretreatment levels during the rest periods, some more durable effects were seen. In 3/6 patients of the GM-CSF group who completed the designed treatment, both WBC and neutrophils remained elevated above the pretreatment levels throughout the 3-month period of treatment, while in one of them thrombocytopenia improved considerably. In the GM-CSF plus AraC group, 4 out of the 7 patients who completed the treatment showed an improvement of neutropenia as well as anaemia. In these 4 patients the BM percentage of blasts was also decreased. In conclusion, the results of this study indicate that GM-CSF given intermittently improves leukopenia in some patients with MDS. In addition, the administration of GM-CSF seems to prevent granulocytopenia of concurrent AraC treatment and may be of benefit in the treatment of these diseases.
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PMID:Treatment of myelodysplastic syndromes with human granulocytic-macrophage colony stimulating factor (GM-CSF) or GM-CSF combined with low-dose cytosine arabinoside. 144 28

Hypoplastic acute leukemia (HAL) is characterized by pancytopenia and by hypocellularity of the bone marrow. The marrow contains equal to or more than 30% myeloblasts. Absence of tissue infiltrates and/or tumor masses is mandatory. Eight patients are described here. They do not fit into the FAB classification for either acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS), except for one patient who subsequently proved to have a chronic myelomonocytic leukemia (CMML). The median age is 65 years. Two patients, including the CMML patient, are alive, 22 and 6 months from diagnosis. Six patients have died. The median survival is 8 months. Normal bone marrow cells cultured either with HAL sera or with HAL peripheral blood mononuclear cells as feeders and exogenous GM-CSF yielded subnormal CFU-GM counts. This might indicate inhibitory activity of HAL serum and defective stimulatory activity of HAL peripheral blood mononuclear cells.
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PMID:Hypoplastic acute leukemia: description of eight cases and search for hematopoietic inhibiting activity. 145 85

The majority of patients suffering from myelodysplastic syndromes (MDS) die of complications due to cytopenia. Clinical trials have demonstrated that in an essential number of MDS patients cytopenia can be ameliorated by exogenously supplied growth factors. We investigated endogenous serum levels of GM-CSF and IL-3 in 15 healthy individuals and 34 patients suffering from MDS. No circulating growth factors were detected in the serum of healthy controls, nor was IL-3 measurable in MDS patients. GM-CSF serum levels, however, were elevated in a significant number of patients (26.5%). Levels did not correlate with FAB classification, leukocyte count or chromosomal abnormalities. No significant differences in GM-CSF or IL-3 receptor expression were detected between healthy individuals and MDS patients. One patient with increased endogenous GM-CSF serum level and normal surface receptor expression responded to exogenously applied GM-CSF. In the light of these results, a functional alteration of growth factor receptors or disturbances of signal transduction pathways must be discussed for MDS.
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PMID:Endogenous serum levels and surface receptor expression of GM-CSF and IL-3 in patients with myelodysplastic syndromes. 146 26

Symptomatic patients with myelodysplastic syndromes (MDS) and 10-30% blasts in the bone marrow were treated with low-dose AraC (2 x 10 mg/m2 subcutaneously (sc) days 1-14) and GM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day sc) given either subsequently (days 15-21) or simultaneously (days 8-14 and one week rest). Evaluations were carried out after three courses (nine weeks); responding patients could be continued for two further cycles. Eighty-two patients with refractory anaemia and excess of blasts (RAEB), with (RAEBt) or without transformation, were evaluable: 45 RAEB and 37 RAEBt, mean age 64 years (range 17-80 years). A complete remission was achieved in 14 cases (17%), 11 had a good response (13%), and 12 a partial response (15%). Stable disease was found in 21 cases (26%). There were 12 cases of toxic death (15%), progression was noted in eight patients (10%), and death due to disease in three (4%). No difference existed between the two treatment arms with respect to response. Major adverse events during treatment were haemorrhage (25%), infections (23%), and fever with GM-CSF (21%). GM-CSF did not induce leukaemia nor contribute to haemorrhage induced by AraC, but gave rise to an overall response rate of 46% which is high and relatively durable as compared to other treatments in this disease.
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PMID:Treatment of myelodysplastic syndromes (MDS) and high leukaemic risk with low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rh GM-CSF). The EORTC Leukaemia Group. 149 35

In conclusion, hematopoietic growth factors have been shown to enhance the recovery and function of circulating WBCs after standard-dose cancer therapy or high-dose cancer therapy with ABMT, and preliminary data strongly suggests that these agents may have the ability to restore leukocyte numbers and competence in AIDS, myelodysplastic syndromes, and other marrow failure states. Phase I and II trials of GM-CSF in patients with AIDS, cancer, marrow failure states, and following bone marrow transplantation have been published, and limited phase III randomized trial experiences have been reported as well. Overall, GM-CSF represents a fascinating molecule with which to modulate human hematopoiesis in vivo. The multilineage stimulatory effects of GM-CSF that are evident in vitro have not been striking or consistent in clinical trials. However, the effects of GM-CSF on the production and function of mature neutrophils, monocytes, and eosinophils have been noted in the vast majority of clinical scenarios in which this cytokine has been tested. The clinical benefits of GM-CSF have, to date, only been proven in large-scale randomized studies of recovery from ABMT for lymphoid neoplasms. However, further data regarding the use of GM-CSF in other clinical settings have been generated, and the final results are eagerly anticipated by the oncology community. The beneficial effects of GM-CSF following ABMT consisted not only of a shorter period of absolute neutropenia, but also fewer significant infections, a diminished requirement for intravenous antibiotic administration, and a shorter overall duration of inpatient hospitalization. The use of GM-CSF in clonal disorders of hematopoiesis, such as myelodysplasia or myeloid leukemias, requires caution before such applications can be routinely recommended, and the demonstration of safety in this setting from large randomized trials will be needed. Preliminary data from small randomized trials suggests that the incidence of evolution to leukemia in patients with myelodysplasia and the number of patients with regrowth of leukemia after induction treatment in relapsed patients with AML may not be significantly different than in patients who do not receive GM-CSF. Various neutropenic conditions (eg, idiopathic or congenital) may respond clinically to hematopoietic growth factors such as GM-CSF. Patients treated for 3 to 15 months continue to respond with significantly increased granulocytes and resolution of prior infection. The subcutaneous route of administration is convenient and patients seem to accept it readily. It is difficult to determine the extent to which adjunctive therapy with GM-CSF will be cost effective.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF): preclinical and clinical investigations. 150 75

A method was devised to grow haemopoietic cells in long-term bone marrow culture (LTBMC) which requires only 1 x 10(6) cells/culture. Such miniature cultures were used to study growth patterns of marrow from patients with myelodysplastic syndromes (MDS). Consistent differences in LTBMC cellularity and cellular composition were noted between MDS and normal marrow. These differences were accentuated by rGM-CSF. The criteria which distinguished between and MDS marrows were: cell count at weeks 1 and 4, % neutrophils and % blasts. In 10 patients with unexplained macrocytosis or pancytopenia miniature LTBMC results clearly segregated into either 'normal' or 'MDS' growth patterns. Miniature LTBMC with rGM-CSF may therefore be a useful diagnostic test for early MDS.
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PMID:A practical miniature long-term bone marrow culture system for investigating early myelodysplasia. 152 61

To assess the effects of GM-CSF in patients with myelodysplasia, a total of 101 patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), and RA with an excess of blasts provided that the percentage of blasts in the bone marrow did not exceed 10% (RAEB) were enrolled in the EORTC Leukemia Cooperative Group study 06885. They were randomized to receive two daily subcutaneous injections of rhGM-CSF (mammalian, glycosylated, Sandoz/Schering-Plough) at a daily dose of either 108 micrograms glycoprotein (group I) or 216 micrograms glycoprotein (group II) for 8 weeks. Response was defined as an increase in Hb (greater than 2.5 g%), neutrophil count (more than 100%), or platelet count (more than 100%) without progression of the disease. After exclusion of 19 patients who did not meet the entry criteria, 82 were evaluated. Fifty-four patients (66%) responded (27 of 42 patients in group I and 27 of 40 in group II). Progressive disease was seen in two patients of group I and in four of group II. Two of the latter developed leukemia. All responses were reflected in the granulocytic series. In two patients platelet numbers also increased. Cytogenetic analysis, successfully performed in 43 cases, showed that 14 of 16 patients with normal karyotypes responded, compared with 14 of 27 patients with abnormal karyotypes (p = 0.008). In some cases GM-CSF was reduced in dose or discontinued prematurely due to side effects so that only 35% of all evaluable patients finished 8 weeks of treatment without a change of dose.
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PMID:A randomized phase-I/II multicenter study of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for patients with myelodysplastic syndromes and a relatively low risk of acute leukemia. EORTC Leukemia Cooperative Group. 158 5

We have tested granulocyte/macrophage-colony-stimulating-factor (rhGM-CSF, fully glycosylated, Sandoz, Schering/Plough) in 40 patients with chemotherapy-induced neutropenia. The drug enhanced leukocyte recovery in 5 different dose levels (2-32 micrograms/kg body weight) if given by continuous intravenous infusion or subcutaneously for 5 days. Patients who received rhGM-CSF during neutropenic infections (n = 32) survived significantly better if they recovered leukocytes to at least 1.5 x 10(9)/l. In patients with myelodysplastic syndromes and excess of blasts (n = 82) remission could be induced in nearly 50% if the drug was given together with low dose cytosine arabinoside (LD-AraC). The results of these phase-II-studies show that rhGM-CSF is a safe drug which may save many patients from life-threatening situations during haematopoietic insufficiency.
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PMID:[Growth factors in therapy of life threatening leukopenia]. 162 26


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