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

As part of a multicenter trial 12 patients with myelodysplastic syndromes (MDS) were treated with 14-day-cycles of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 250 micrograms/m2 day s.c.). In addition, all patients received 20 mg/m2/day s.c. cytosine-arabinoside (Ara-C) 12 h after GM-CSF except for patients suffering from refractory anemia (RA) according to FAB classification. Courses were repeated after 4 weeks. In 11 evaluable patients, results according to FAB-classified MDS were as follows: RA, 1/2 response (R), 1/2 stable disease (SD); RAEB, 2/3 R, 1/3 SD; RAEB-T, 1/6 CR, 1/6 PR, 2/6 R, 2/6 progression; CMML, 1/2 SD. In 2 patients with RAEB-T, overt acute myeloid leukemia was observed 2 and 10 weeks after initiation of treatment. With few exceptions, treatment resulted in a prompt increase in granulocytes and eosinophiles. This was associated with improvement of infectious complications. Increases in red cells and platelets occurred variably and was apparently associated with responses of the underlying disease. Dose limiting side effects consisted of fever, severe fatigue and dolent local reactions at the site of GM-CSF injection. In addition, nausea and diarrhoea occurred frequently. Less often, respiratory and cardiovascular side effects were encountered. In summary, GM-CSF +/- Ara-C in MDS results in objective remission with manageable toxicity. Conceivably, this regimen will serve as a base for future treatment strategies against MDS.
 ...
PMID:Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosine-arabinoside in the treatment of patients with myelodysplastic syndromes. A phase II study. 218 22

GM-CSF has been used in clinical trials to assess its role in promoting the proliferation and differentiation of marrow cells and enhancing the functional activities of granulocytes and monocytes. These studies have indicated that GM-CSF may prove useful in the management of cancer patients by preventing or treating myelosuppression following cancer chemotherapy and in patients with myelodysplasia or aplastic anaemia. As well as determining the efficacy of GM-CSF as a therapeutic agent, these studies are also providing insights into the possible roles of GM-CSF in vivo. Pharmacokinetic studies of GM-CSF in patients with advanced cancer and myelodysplasia suggest that the ratio of efficacy to toxicity of GM-CSF can be modified by changing either the dose or the method of administration.
 ...
PMID:The potential role of granulocyte-macrophage colony stimulating factor (GM-CSF) in cancer chemotherapy. 227 11

Based on the results of preclinical and in vitro studies demonstrating enhanced granulocytic proliferation and differentiation induced by granulocyte-monocyte and granulocyte-colony stimulating factors (GM-CSF and G-CSF), these recombinant human haemopoietic growth factors have been used to treat cytopenic patients with myelodysplastic syndromes (MDS). Laboratory investigations have shown responsiveness of enriched haemopoietic precursors in vitro to the proliferative and granulocytic differentiative stimuli of G-CSF, generally without increased clonal regeneration. To date, five short-term phase I/II clinical trials using GM-CSF have demonstrated that 38 of 45 treated patients had improvements in neutrophil counts, 14 had increased reticulocyte counts, with three of these patients having decreased red blood cell transfusion requirements, and eight had a transient increase in platelets. In 12 patients an increase in marrow and/or peripheral blood blasts was noted. Seven patients progressed to acute myeloid leukaemia (AML), particularly patients with greater than 15% marrow blasts. In a longer term study, five patients received GM-CSF for two to nine weeks, although only one maintained increased neutrophil counts, one developed antibodies to GM-CSF and one's condition evolved into AML. Eighteen patients have been treated for two months in phase I/II clinical trials with G-CSF, 16 of whom had normalization of neutrophil counts with improved marrow maturation, five had increased reticulocyte counts with three having decreased transfusion requirements, four had transient increases in blasts and no substantial changes in platelet counts were noted. Eleven patients have received maintenance therapy with G-CSF for 6-16 months and 10 had persistent increases in neutrophil counts with enhanced marrow myeloid maturation. Decreased infectious episodes were noted in these patients at times at neutrophil improvements. Four of the 18 patients have subsequently developed AML after 6-16 months. Both CSFs were well tolerated, although the incidence of fever, myalgias and bone pain was more prominent in patients receiving GM-CSF at higher doses. In vitro correlates with these in vivo results were demonstrated as laboratory studies showed that G-CSF had greater myeloid differentiative and less proliferative effects for MDS marrow than did GM-CSF. Marrow cytogenetic studies after treatment generally indicated persistence of the initial normal and/or abnormal clones. These studies have demonstrated that both G-CSF and GM-CSF improve neutrophil counts in a high proportion of patients with MDS and that chronic administration of G-CSF elicits persistent neutrophil responses and may decrease infections. Phase III controlled trials are required to determine whether the natural history of this disorder will be altered by use of colony stimulating factors.
 ...
PMID:The use of haemopoietic growth factors in the treatment of myelodysplastic syndromes. 227 14

The nosography of the dyserythropoietic syndromes remains poorly defined in the field of clinical hematology. The prominent pathophysiologic feature lies in the "ineffective erythropoiesis" as expressed by bone marrow erythroid hyperplasia with dysplasia accompanied by a normal or only slightly increased reticulocyte count. Both erythrokinetics and ferrokinetics are impaired, as shown by either slight reduction of the red cell survival or marked increased rate of serum iron transport together with reduced cellular iron utilization. The dyserythropoietic syndromes can be classified as acquired, secondary or congenital. The acquired ones, especially the sideroblastic forms, belonging to the myelodysplastic syndromes, are typical of the elderly whereas the congenital are of childhood. Their treatment is still a matter of controversy. However, the employment of folic acid, Vit. B12, pyridoxine and androgens can be useful in selected cases. In case of severe anemia, blood transfusion are required in association with iron chelating agents. However, some biological molecules, such as erythropoietin, interleukins 3 and 4, hemopoietic growth factors (especially GM-CSF), could represent future prospects of treatment.
 ...
PMID:[Dyserythropoietic syndromes: incidence, diagnosis, therapy]. 229 Oct 9

Conditioned media (CM) from a human lung adenocarcinoma cell line expressing interleukins 1 and 6 (IL-1, IL-6), granulocyte (G), macrophage (M), and GM colony-stimulating factors (G, M, GM-CSF) and transforming growth factor beta (TGF beta) were used to stimulate growth of bone marrow (BM) cells from 18 persons with leukemia, myelodysplastic syndrome, or lymphoma. The objective was to increase numbers of analyzable metaphases and to enhance the likelihood of detecting cytogenetic abnormalities. Although more mitotic cells were observed with CM, the detection rate of cytogenetic abnormalities decreased in 12 of 18 cases. These data indicate that use of CM for cytogenetic analyses may favor growth of normal versus leukemia cells and mask cytogenetic abnormalities.
 ...
PMID:Use of conditioned media in cell culture can mask cytogenetic abnormalities in acute leukemia. 233 74

The major hematopoietic growth factors have been produced through recombinant DNA technology and have entered initial clinical trials; results of these trials will be reviewed here. Granulocyte colony-stimulating factor (G-CSF) has been tested in patients with bladder cancer and small-cell carcinoma of the lung. In these studies, G-CSF ameliorated the leukopenia associated with combination chemotherapy, reduced the incidence of mucositis in the bladder cancer patients, and nearly eliminated the occurrence of serious infections in the lung cancer patients. Trials involving another factor, granulocyte macrophage colony-stimulating factor (GM-CSF), have resulted in a marked increase in white blood cell (WBC) counts in patients with myelodysplastic syndromes, and has accelerated the appearance of leukocytes and platelets after autologous bone marrow transplants. GM-CSF can also increase the WBC counts in acquired immunodeficiency syndrome patients treated with zidovudine. Both G-CSF and GM-CSF may produce multilineage effects in certain clinical settings and dose ranges. Finally, interleukin-1 (IL-1) and IL-3, which commit very early stem cells to a myeloid pathway, may be used in combination with G-CSF or GM-CSF to produce a synergistic response to various clinical situations.
 ...
PMID:Status of colony-stimulating factors in cancer and AIDS. 240 93

Hemopoietic lineage commitment can be breached by concomitant expression of the c-myc and v-raf oncogenes. Switching to the myeloid lineage occurred frequently when B lineage cells, from either lymphomas or preleukemia bone marrow cells of Emu-myc transgenic mice, were infected with a retrovirus bearing v-raf. Cloned pre-B and B cell lines changed into either mature or immature macrophages as assessed by morphology, adherence, phagocytic activity, surface markers, and lysozyme production, but retained clonotypic immunoglobulin gene rearrangements. Although expression of the Emu-myc transgene was reduced or abolished in the more differentiated lines, the lines remained tumorigenic. The converted lines produced the myeloid growth factor GM-CSF, and most had karyotypic alterations. These results suggest that constitutive myc plus raf expression can provoke genetic reprogramming in lymphocytes.
 ...
PMID:Hemopoietic lineage switch: v-raf oncogene converts Emu-myc transgenic B cells into macrophages. 245 46

Two cases of myelodysplastic syndrome (MDS) were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF). In both cases, an increase of peripheral neutrophil counts was noted with a peak within 12 hr after the rhG-CSF administration. Neutrophils with ring shaped or hypersegmented nuclei were noted in the peripheral blood during the treatment, and they disappeared promptly after discontinuation of the therapy. The results indicate that the rhG-CSF might have mobilizing and differentiating effects on neutrophils derived from the MDS clone.
 ...
PMID:Morphologic changes of neutrophils in myelodysplastic syndrome treated with recombinant human granulocyte colony-stimulating factor. 245 90

[3H]thymidine uptake by NFS-60 cells in microcultures was found to increase in a linear fashion with the increasing doses of purified recombinant human granulocyte colony-stimulating factor (rhG-CSF). Such increases were found neither with rhG-CSF samples pretreated with rabbit anti-rhG-CSF serum nor with other human colony-stimulating factors such as granulocyte-macrophage colony-stimulating factor (hGM-CSF) or macrophage colony-stimulating factor (hM-CSF). Based on these findings, sera from normal persons and patients with severe infections or various hematological disorders were tested after dialysis using this system in order to determine whether G-CSF levels in sera can be estimated or not. In ten normal persons, five patients with acute myelogenous leukemia (AML M1, M2, and M3), five with myelodysplastic syndrome, and four with chronic myelogenous leukemia, no increases in [3H]thymidine uptake were found within the dose range of 0.4 microliters to 50 microliters. In contrast, linear dose responses parallel to a G-CSF standard curve were observed in one patient with a severe bacterial infection, four with aplastic anemia, two with acute myelomonocytic leukemia (AMMoL) (M4), and two with idiopathic neutropenia tested. From the standard curve, the probable levels of G-CSF were calculated as follows: approximately 200 pg/ml with infection, 130-220 pg/ml with aplastic anemia, 150 and 200 pg/ml with AMMoL, and 1120 and 1200 pg/ml with idiopathic neutropenia. The activities of sera were reduced by the anti-rhG-CSF serum pretreatment in the same way as documented in the case of rhG-CSF. Furthermore, the level in a patient with a severe infection became undetectable soon after elimination of the infection and blood neutrophil counts had returned to normal. These findings indicate that the microbioassay system will be useful for measuring circulating G-CSF levels which would fluctuate in accord with requirements for stimulating neutrophil production or with abnormal production of hG-CSF.
 ...
PMID:A new bioassay for human granulocyte colony-stimulating factor (hG-CSF) using murine myeloblastic NFS-60 cells as targets and estimation of its levels in sera from normal healthy persons and patients with infectious and hematological disorders. 246 30

The myeloid growth factors are a promising new class of therapeutic agents with the potential for broad clinical application. Four recombinant myeloid growth factors, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin (IL)-3 are available for clinical trials. GM-CSF has been studied in leukopenia related to acquired immunodeficiency syndrome (AIDS), aplastic anemia, and myelodysplasia, as well as in patients receiving chemotherapy and those undergoing autologous bone marrow transplantation. In these trials, GM-CSF was demonstrated to increase the number of neutrophils, eosinophils, and monocytes with corresponding bone marrow changes. Toxicity is dose-related, and maximum tolerated dosages are in the range of 16 to 32 micrograms/kg/day. The effects of daily subcutaneous administration of GM-CSF appear to be similar to those of intravenous (IV) administration. G-CSF, studied mainly in the treatment of neutropenia following cytotoxic chemotherapy, was found to decrease the duration of severe neutropenia as well as the risk of infections. G-CSF causes prominent increases in neutrophil levels without affecting eosinophils or monocytes. Associated toxicity is minimal, and subcutaneous administration is efficacious. Preliminary evidence suggests that G-CSF may also have a therapeutic role in indolent lymphoid neoplasms complicated by neutropenia. Administration of natural M-CSF to patients receiving chemotherapy and those with chronic childhood neutropenia has shown modest neutrophil increases. Preclinical data on IL-3 suggest that this agent increases neutrophils, eosinophils, basophils, reticulocytes, and possibly platelets.
 ...
PMID:Clinical applications of the myeloid growth factors. 247 Dec 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>