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

In a pilot study, five patients with myelodysplastic syndromes with an excess of blast cells were treated with a combination of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and low-dose cytosine-arabinoside (ara-C) in an attempt to selectively kill the leukemic blast cells and thereby to restore normal hemopoiesis. The treatment schedule consisted of three 14-day-cycles of 250 micrograms/m2 rhGM-CSF and 20 mg/m2 ara-C given daily s.c. with four-week treatment-free intervals. In all four evaluable patients the percentage of bone marrow blast cells decreased significantly with an increase in the mature myeloid cells but without bone marrow aplasia. Toxic side effects attributable to the drugs were minor with fever, mild bone pain, erythema and itching at the site of subcutaneous injection of rhGM-CSF. In conclusion, the combined therapy of rhGM-CSF and low-dose ara-C appears to be effective in the short-term control of the leukemic cell population.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosine arabinoside in patients with myelodysplastic syndrome. A pilot study. 265 86

The conversion of normal haemopoietic stem cells to myelodysplastic and then to leukaemic cells is marked by a number of events leading to progressive genetic changes in the abnormal clonal population. Cytogenetic evidence points to abnormalities at specific chromosomal locations, commonly involving chromosomes 5 and 7, where there are a particular concentration of genes directly involved in the regulation of haemopoietic proliferation and differentiation. These include GM-CSF, IL-3, M-CSF, erythropoietin and others. Other genes that may be involved in the preleukaemic process are so-called 'oncogenes' such as met on chromosome 7q and fms on 5q (which codes for the M-CSF receptor) that may be deleted or translocated. The ras gene family is activated by point mutations in a wide variety of malignant states, including myelodysplasia and acute myeloblastic leukaemia. At the present time we do not know the cause of these genetic lesions, their functional significance or the sequence in which they occur.
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PMID:Oncogenes in the myelodysplastic syndrome. 267 42

In 13 patients with myelodysplastic syndrome (MDS) mature and immature erythropoietic (CFU-E, BFU-E), granulopoietic (CFU-GM) and megakaryopoietic (CFU-Meg) colony formation from human bone marrow mononuclear cells was evaluated in a microagar culture system. All but three patients exhibited abnormal CFU-Meg. The defect of CFU-Meg paralleled the reduction of BFU-E, whereas CFU-GM number declined to a lesser extent. Not only the CFU-Meg number, but also the number of megakaryocytes (Mk) per colony was reduced suggesting an additional functional CFU-Meg defect. Megakaryocytic growth factor (Meg-CSF) abnormalities in MDS patients were detected using normal nonadherent T-lymphocyte depleted bone marrow cells as target cells for serum testing. Even for sera from patients with a reduction of platelets and bone marrow megakaryocytes Meg-CSF levels were not increased. No cellular or humoral inhibition could be detected in an MDS patient with a 5q- karyotype, who had an isolated defect of the megakaryocytic cell lineage at presentation. Some patients revealed a spontaneous formation of mixed erythrocytic, granulocytic and megakaryocytic clusters in the presence of fetal calf serum or autologous patient serum, probably representing autonomous proliferation of the malignant clone. In conclusion, both cellular and humoral factors can cause abnormalities of the megakaryocytic cell lineage in MDS patients.
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PMID:Abnormal megakaryopoiesis in patients with myelodysplastic syndromes: analysis of cellular and humoral defects. 267 61

Colony-stimulating factors (CSFs) are a family of regulatory glycoprotein hormones that promote the proliferation and differentiation of hemopoietic progenitor cells and augment the functions of mature effector cells in vitro. The recent cloning of human genes and the availability of sufficient quantities of recombinant purified growth factors have made it possible to evaluate their therapeutic potential in cytopenic states. Initial studies with GM-CSF have demonstrated its ability to increase neutrophil, monocyte, and eosinophil counts in patients with acquired immune deficiency syndrome (AIDS), myelodysplastic syndrome (MDS), and aplastic anemia. Both GM-CSF and G-CSF reduce the duration of neutropenia following chemotherapy and accelerate hematopoietic recovery in patients undergoing intensive chemotherapy and autologous bone marrow transplantation. Studies are now ongoing to determine the optimal dose, route, schedule of administration, and long-term effects. While the appropriate settings for the use of different CSFs remain to be determined, the initial results of clinical trials are of great interest and suggest that hematopoietic growth factors will play an important role in several clinical arenas.
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PMID:Clinical applications of colony-stimulating factors. 268 11

Clinical usefulness of G-CSF, GM-CSF and M-CSF was summarized. These CSFs had been demonstrated to accelerate the recovery from neutropenia after anti-cancer chemotherapy and bone marrow transplantation. CSFs were also effective in some patients with aplastic anemia, myelodysplastic syndrome (MDS) and idiopathic neutropenia among children. An increase of neutrophils was observed in these patients responding to CSFs. Few patients with aplastic anemia and MDS, however, responded to G-CSF with an increase of reticulocytes and thrombocytes in addition to neutrophils. Combination of G-CSF with anti-leukemic agents for the treatment of refractory and relapsed acute non-lymphocytic leukemia (ANLL) or as the conditioning for bone marrow transplantation to refractory ANLL patients was found to be quite effective. Possible usage of GM-CSF and M-CSF for cancer treatment by stimulating anti-cancer functions of monocytes-macrophages was also discussed. Furthermore, GM-CSF and M-CSF were demonstrated to decrease serum cholesterol level in rabbits as well as in patients. Possible mechanism of this cholesterol-lowering effect was also discussed.
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PMID:[Colony stimulating factor]. 281 7

We have examined the efficacy of various drugs in 44 patients with MDS and found the different effectiveness which depends on the type of MDS. Namely, RA appears to respond to steroid hormone, androgen, and/or vitamin D3, regardless of single or combined use. In particular, it is obvious in androgen, and as our previous reports, high content of acidic ferritin in RBC with RA have changed to more basic ones by treatment with androgen. On the contrary, these drugs were not effective on RAEB, RAEB-T, and CMML. A long-term observation is needed to determine whether the prolonged or decreased occurrence of leukemia could be obtained in the effective cases with RA. Most of the cases who did not develop overt leukemia during this study died of bleeding or infections due to thrombocytopenia or leukocytopenia, thus indicating that supportive therapies are important in patients with MDS. Since it has recently been reported that recombinant G-CSF or GM-CSF is helpful to increase the number of leucocyte and to enhance their functional recovery in MDS, these factors may be powerful agents against infections when they are carefully used with regard to the activation of leukemic clones.
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PMID:[Therapy of the preleukemic state: effect of androgens on refractory anemia]. 283 1

We examined the in vitro effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophil anomalies in 20 patients with myelodysplastic syndromes (MDS) and eight patients with chronic myelogenous leukemia (CML). Neutrophil alkaline phosphatase (NAP) activity was determined in nine MDS patients and eight CML patients by a scoring method. NAP scores were decreased in six of the nine patients with MDS and in all of the patients with CML. In all patients with these diseases, NAP scores increased by incubating the blood with rhG-CSF. An increase in NAP scores by rhG-CSF was observed even at a concentration of 1 U/mL in patients with MDS but was observed only at higher concentrations (1,000 to 10,000 U/mL) in patients with CML. Significant increases in NAP scores occurred at 12 hours' incubation in patients with MDS, whereas the increase was more gradual in patients with CML. This time course difference was thought to be due mainly to the difference in cell populations of circulating myeloid cells between MDS patients and CML patients. Induction of NAP activity by rhG-CSF in patients with both these diseases was suppressed by the addition of inhibitors of RNA or protein synthesis. Neutrophil superoxide anion (O2-) production induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was determined in the other 11 patients with MDS. This neutrophil function was decreased in seven of the 11 patients with MDS, normal in two patients, and increased in two patients. Preincubation with rhG-CSF caused a significant increase in fMLP-induced O2- production in nine of the 11 patients with MDS. rhG-CSF enhanced this neutrophil function in a time- and dose-dependent manner, and maximal stimulation was observed at 2,000 to 4,000 U/mL of rhG-CSF and at five to ten minutes' incubation. The present results show that rhG-CSF is able to repair at least in part the neutrophil anomalies in these patients, and our data, especially for patients with MDS, suggest the clinical usefulness of rhG-CSF for this preleukemic disorder.
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PMID:Recombinant human granulocyte colony-stimulating factor repairs the abnormalities of neutrophils in patients with myelodysplastic syndromes and chronic myelogenous leukemia. 303 12

The availability of rhGM-CSF has allowed the in vivo treatment of patients with cytopenia. Therefore, a phase I-II trial was initiated to study the effect of rhGM-CSF in patients with myelodysplastic syndromes who were not eligible for other kinds of therapy. rhGM-CSF has been tested in 10 patients in doses from 15 micrograms/m2 to 150 micrograms/m2 given intravenously over 8 hours for a cycle of 7 days followed by an interval of 14 days and a second 7-day treatment course. A dose-dependent increase in leukocyte count was observed in 9 of 10 patients. No change in reticulocyte numbers was seen and only one patient experienced an increase in platelet count. Toxicity mainly consisted of mild phlebitis at the site of infusion and sternal pain after bolus injection. An increase in blast cell counts in some patients necessitated the start of low-dose Ara-C therapy.
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PMID:In vitro and in vivo action of recombinant human GM-CSF (rhGM-CSF) in patients with myelodysplastic syndromes. 306 85

The availability of rh GM-CSF has allowed the in vivo treatment of patients with cytopenia. Therefore a phase I/II trial was initiated to study the effect of rh GM-CSF in patients with myelodysplastic syndromes who were not eligible for other kinds of therapy. rh GM-CSF has been tested in 10 patients in doses from 15 micrograms/m2 to 150 micrograms/m2 given intravenously over 8 hours for a cycle of 7 days followed by an interval of 14 days and a second 7-day treatment course. A dose dependent increase in leukocyte count was observed in 9 out of 10 patients. No change in reticulocyte numbers was seen and only one patient experienced an increase in platelet count. Toxicity mainly consisted of mild local phlebitis at the site of infusion and sternal pain after bolus injection. An increase in blast cell counts in some patients necessitated the start of low dose Ara-C therapy.
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PMID:Phase I/II study with GM-CSF in patients with myelodysplastic syndromes. 307 28

We performed a Phase I/II study of the administration of recombinant human GM-CSF to patients suffering from severe bone marrow failure, either due to aplastic anemia or myelodysplastic syndrome. Doses ranging from 15 micrograms/m2 to 480 micrograms/m2 were administered as an intravenous infusion daily for 7 days. Temporary improvements were seen in granulocyte counts, monocyte counts and reticulocyte counts. There was no reduction in erythrocyte transfusion requirements and no effect was observed on platelet counts. There was only minimal toxicity consisting of transient low back discomfort, anorexia, myalgias/arthralgias, and low grade fever. Our data suggest that prolonged use of GM-CSF might benefit some patients with severe marrow failure.
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PMID:Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in bone marrow failure. 307 31


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