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)

Twenty-one patients with myelodysplastic syndrome (MDS) or overt leukemia resulting from MDS were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and cytosine arabinoside (Ara-C). Ara-C was administered in a dose of 20 mg/m2 every 12 h for 5 days and after 2 days 125 micrograms of rhG-CSF was administered for 10 days. After recovery of the leukocyte count the therapy was repeated, doubling the dose of Ara-C serially when possible. Of 13 patients with MDS, four achieved complete remission (CR), two good response (GR), two minor response (MR), and five no response (NR). Of eight patients with overt leukemia from MDS, only one with hyperplastic bone marrow achieved a partial response (PR) and the remaining seven achieved NR. The efficacy of the combination of rhG-CSF and Ara-C in the treatment of MDS and its leukemic phase is discussed, including at which time rhG-CSF should be administered: before, after or concomitantly with Ara-C. Multicenter randomized studies are needed in the evaluation of this combination therapy.
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PMID:Treatment with cytosine arabinoside and granulocyte colony-stimulating factor in patients with myelodysplastic syndrome and its leukemic phase. 753 31

We report a patient with refractory anemia with excess blasts who showed a lineage-unrestricted hematologic response to granulocyte colony-stimulating factor (G-CSF). After 17 months of a stable disease state, the patient developed pneumonia, progression of cytopenia, and reduced cellularity and blast mass in the bone marrow. He was given G-CSF to overcome the pneumonia. Not only the neutrophil count, but also the platelet count increased soon after initiation of the G-CSF therapy; both counts became normal on the fifth day of the G-CSF therapy. Additionally, the anemia improved gradually. The neutrophil and platelet counts were maintained in the normal range for 3 months after cessation of the G-CSF. In vitro studies showed that G-CSF alone stimulated megakaryocyte colony formation from bone marrow mononuclear cells (BMMNC), and accessory cells in the BMMNC were necessary for expression of this G-CSF-induced in vitro megakaryocytopoiesis. These results suggest that, in coordination with accessory cells, G-CSF stimulated megakaryocytopoiesis in the patient. This case provides valuable information for understanding the mechanisms of a lineage-unrestricted hematologic response to G-CSF, which is very rarely observed in MDS.
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PMID:Lineage-unrestricted hematologic response to granulocyte colony-stimulating factor in a patient with refractory anemia with excess blasts. 753 78

Thirteen cases, including 10 relapse cases, of refractory acute myeloid leukemia (AML) (aged 17-70, median 46) by cytosine arabinoside (Ara-C) combined with granulocyte colony-stimulating factor (G-CSF) simultaneously to enhance the sensitivity to Ara-C. Low dose Ara-C (10-40 mg/day) combined with G-CSF was administered in most of them. Complete (CR) and partial remission (PR) were achieved in 5 and 4 patients, respectively, and response (CR + PR) rate was 69.2%. We obtained 5 CRs and 3 PRs in 10 patients with relapsed AML. However, CR and PR duration was short in all cases. None of the 3 patients with MO, AML transformed from myelodysplastic syndrome (MDS), and de novo AML with trilineage myelodysplasia (TMDS) had any response. There was no leukemic colony formation in the culture medium containing G-CSF in the nonresponding patients. The combination therapy caused severe myelosuppression, and most patients experienced prolonged neutropenia, and suffered from infections. In some patients enhanced chemosensitivity of leukemic cells induced by G-CSF was indicated but, the effect of this approach must be determined by large scale controlled studies.
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PMID:[Trial of combined cytosine arabinoside with granulocyte colony-stimulating factor therapy or refractory acute myeloid leukemia]. 756 92

Monosomy 7 (Mo7) and leukaemia predisposition are associated with Kostmann's disease (KD). The recent introduction of long-term recombinant HuG-CSF treatment in patients with KD, whilst showing significant reductions in infectious complications and improved quality of life, might also be associated with an increased risk of developing karyotypic abnormalities, myelodysplasia (MDS) and acute myeloid leukaemia (AML). We describe a case of an identical twin with probable autosomal dominant KD who developed anaemia, Mo7/MDS and AML at 18, 30 and 50 months respectively from starting r-metHuG-CSF (filgrastim) treatment. Further patient analyses are required to establish the natural history of KD and to determine what role, if any, filgrastim plays in altering the pathobiology of this disorder.
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PMID:Kostmann's disease, recombinant HuG-CSF, monosomy 7 and MDS/AML. 757 23

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

In hematological diseases such as myeloproliferative disorders (MPD) or myelodysplastic syndromes (MDS), some abnormalities in the chemiluminescence of neutrophils are observed. There are two groups; one includes chronic myelogenous leukemia (CML), essential thrombocythemia (ET) and MDS, which all have decreased chemiluminescence of neutrophils. The other group includes polycythemia vera (PV) which has increased neutrophil chemiluminescence. We studied the neutrophil function by analyzing the chemiluminescence in 35 patients with hematological diseases. In most of these cases the defects in chemiluminescence in 35 patients with hematological diseases. In most of these cases the defects in chemiluminescence in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) were correlated with those in response to phorbol 12-myristate 13-acetate (PMA). But there were exceptional cases in which the maximal light emission of chemiluminescence (Max CL) in response to FMLP was obviously lower than controls despite the fact that the Max CL in response to PMA was the same as the controls. These facts suggest a heterogenicity of the defect site in these diseases. There was a correlation between the level of chemiluminescence and the neutrophil alkaline phosphatase (NAP) activity in these patients. In vitro culture of CML neutrophils with granulocyte colony-stimulating factor (G-CSF) showed a correlation between the increase in the level of chemiluminescence and NAP activity. These results suggest that NAP may take part in the control of neutrophil function.
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PMID:Chemiluminescence of neutrophils in patients with myeloproliferative or myelodysplastic hematologic diseases--relation to neutrophil alkaline phosphatase activity. 768 68

We treated myelodysplastic syndrome patients (MDS) with both recombinant human granulocyte colony-stimulating factor (G-CSF) and recombinant human erythropoietin (EPO) to determine whether such combination therapy resulted in improvement of their anemias. Twenty-four of 28 patients begun on study completed the protocol and were evaluable for erythroid responses. Therapy was initiated with G-CSF at 1 micrograms/kg administered by daily subcutaneous injection and adjusted to either normalize or double the neutrophil count. EPO was then administered by daily subcutaneous injection at a dose of 100 U/kg and dose-escalated to 150 and 300 U/kg every 4 weeks while continuing the G-CSF. Changes in absolute reticulocyte count, hematocrit level, and need for RBC transfusions were compared with pretreatment values as well as other blood cell counts. Ten of 24 patients (42%) had erythroid responses, whereas all patients had neutrophil responses. Six previously transfused patients no longer required RBC transfusions during the treatment period. Erythroid responses were found to be independent of patient age, French-American-British subtype, duration of disease, prior RBC transfusion requirements, or cytogenetic abnormalities at presentation. Pretreatment serum EPO levels were lower in erythroid-responding as compared with nonresponding patients (median 157 v 600 U/L; P = .05). The combined treatment modality was generally well tolerated. We conclude that a substantial percentage of MDS patients had both erythroid and myeloid responses when treated with the combination of G-CSF and EPO.
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PMID:Treatment of the anemia of myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin. 752 Jul 83

The chromosomal translocation t(3;21)(q26;q22), which is found in blastic crisis in chronic myelogenous leukemias and myelodysplastic syndrome-derived leukemias, produces AML1/Evi-1 chimeric transcription factor and is thought to play important roles in acute leukemic transformation of hemopoietic stem cells. We report here the functional analyses of AML1/Evi-1. It was revealed that AML1/Evi-1 itself does not alter the transactivation level through mouse polyomavirus enhancer-binding protein 2 (PEBP2; PEA2) sites (binding site of AML1) but dominantly suppresses the transactivation by intact AML1, which is assumed to be a stimulator of myeloid cell differentiation. DNA-binding competition is a putative mechanism of such dominant negative effects of AML1/Evi-1 because it binds to PEBP2 sites with higher affinity than AML1 does. Furthermore, AML1/Evi-1 stimulated c-fos promoter transactivation and increased AP-1 activity, as Evi-1 (which is not normally expressed in hemopoietic cells) did. Experiments using deletion mutants of AML1/Evi-1 showed that these two functions are mutually independent because the dominant negative effects on intact AML1 and the stimulation of AP-1 activity are dependent on the runt domain (DNA-binding domain of AML1) and the zinc finger domain near the C terminus, respectively. Furthermore, we showed that AML1/Evi-1 blocks granulocytic differentiation, otherwise induced by granulocyte colony-stimulating factor, of 32Dcl3 myeloid cells. It was also suggested that both AML1-derived and Evi-1-derived portions of the fusion protein play crucial roles in this differentiation block. We conclude that the leukemic cell transformation in t(3;21) leukemias is probably caused by these dual functions of AML1/Evi-1 chimeric protein.
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PMID:Dual functions of the AML1/Evi-1 chimeric protein in the mechanism of leukemogenesis in t(3;21) leukemias. 773 22


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