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)

Activation of the N- and K-ras proto-oncogenes is the most common molecular abnormality in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In retrospective studies, approximately 3-36% of MDS patients were reported to harbor a mutated ras proto-oncogene, with some series suggesting the presence of ras-mutations are associated with progressive disease and a poor prognosis. Since hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) are currently used for therapy in MDS but may stimulate the proliferation of leukemic cells, we assessed the frequency and significance of ras mutations in 27 MDS patients, 15 of whom underwent G-CSF therapy. Patients were analyzed for the presence of mutations in codons 12, 13, and 61 of the N- and K-ras proto-oncogenes. Only three patients (11%, two refractory anemia with excess of blasts (RAEB), one RAEB in transformation (RAEB-T)) harbored activated ras oncogenes with the mutations localized in N-ras codons 12 and 61. Patients were followed for periods of up to 4 years or until death supervened. Patients exhibiting ras mutations were no more likely to develop AML compared to ras-negative patients (1/3 vs. 10/24) or to have decreased survival (p = 0.64). These data indicate that, in this group of MDS patients, ras mutations do not appear to correlate with a poor prognosis, and do not adversely interact with exogenously administered G-CSF.
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PMID:Mutations in the ras proto-oncogenes in patients with myelodysplastic syndromes. 751 75

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) and erythropoietin (rhE-PO) were used to treat ten patients with myelodysplastic syndromes (MDS). None of the patients showed a favorable response in erythrocyte and platelet counts following 10 weeks' treatment, although favorable responses in neutrophil counts were observed in eight of ten patients (80.0%) and in seven of eight patients (87.5%) following 2 weeks' and 10 weeks' treatment, respectively. However, one patient with refractory anemia had a delayed favorable response in erythrocyte and neutrophil counts at week 14 in spite of the cessation of combination therapy at week 10. These results indicate that combination therapy with rhG-CSF and rhEPO is not beneficial to patients with MDS, based on the presently used protocol.
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PMID:Failure of combination therapy with recombinant granulocyte colony-stimulating factor and erythropoietin in myelodysplastic syndromes. 751 90

A patient with aplastic anaemia developed Sweet's syndrome (a febrile neutrophilic dermatosis) during granulocyte colony-stimulating factor (G-CSF) therapy. Three repeated episodes of appearance and disappearance of erythematous nodules after administration and withdrawal of G-CSF confirmed that G-CSF induced Sweet's syndrome in the patient. Sweet's syndrome has been reported in patients with myelodysplastic syndrome and acute leukemia, but not in patients with aplastic anaemia. This is the first report of a patient with aplastic anaemia who developed G-CSF-induced Sweet's syndrome.
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PMID:Sweet's syndrome during therapy with granulocyte colony-stimulating factor in a patient with aplastic anaemia. 751 39

We report a patient with refractory anaemia with excess blasts in transformation (RAEB-t) who presented with severe pancytopenia and received four intermittent series of granulocyte colony-stimulating factor (G-CSF) treatment over 1.5 years. In addition to the increase in mature neutrophils, platelet count and haemoglobin level were dramatically increased. These haematological improvements were dependent on G-CSF during these treatment series. Bone marrow colony assay revealed that G-CSF increased both CFU-E- and BFU-E-derived colonies in vitro. Clinical usage of G-CSF in myelodysplastic syndrome (MDS) is discussed, with particular emphasis on mechanisms of trilineage response.
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PMID:Marked and reproducible increase in trilineage blood cell counts by administration of granulocyte colony-stimulating factor in a patient with refractory anaemia with excess blasts in transformation. 751 41

A 42-year-old man was admitted to our hospital because of pancytopenia in April 1992. A diagnosis of refractory anemia was made. The karyotype was normal male type on the initial study. Subcutaneous administration of granulocyte colony-stimulating factor (G-CSF) initially increased the peripheral neutrophil count, bat in January 1993, although blast cells did not increase, neutrophils had decreased in spite of the continuation of G-CSF administration. Chromosome analysis showed 46XY, +Y, -7 at this point. By adding 50 mg of cytarabine ocfosfate (SPAC) daily, the peripheral neutrophil count again rose dramatically. However, anemia, thrombocytopenia and the chromosomal abnormality were unchanged. These results indicate that SPAC may upregulate the effect of G-CSF on granulopoiesis in patients with myelodysplastic syndrome.
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PMID:[Effects of cytarabine ocfosfate on colony-stimulating factor in myelodysplastic syndrome with monosomy 7]. 752 5

Fludarabine (Fludara) is a new purine analogue that was first entered into clinical trials in 1982. Results of initial studies with high dosages (> 96 mg/m2/day for 5 to 7 days) of fludarabine in acute leukaemia showed significant cytoreductive activity but a high incidence of severe irreversible neurotoxicity. The results of subsequent studies with lower dosages of 25 to 30 mg/m2/day for 5 days in chronic lymphocytic leukaemia (CLL) and low grade lymphomas have shown this regimen to be effective and safe, with almost no significant neurotoxicity. At present, the major role of fludarabine in leukaemia is in the management of CLL. In previously treated patients with CLL, responses are obtained in more than 50% of patients, with two-thirds of those responses being complete remissions according to the National Cancer Institute Working Group (NCIWG) criteria for complete response and partial response. The major causes of morbidity associated with fludarabine in CLL are infections and febrile episodes. These occur more frequently in previously treated patients and those with advanced stage of disease. Myelosuppression is dose limiting and a small proportion of patients with CLL develop moderate to severe and sometimes protracted myelosuppression. Administration of combined fludarabine and cytarabine (cytosine arabinoside; ara-C) alone (FA regimen) or together with granulocyte colony-stimulating factor (FLAG regimen) produced high response rates in previously treated refractory patients with acute leukaemia and previously untreated patients with acute myelogenous leukaemia or myelodysplastic syndrome. The wide range of biochemical and biological activities of fludarabine suggests that it will have an expanding role in future combinations in the treatment of both acute and chronic leukaemias.
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PMID:Clinical experience with fludarabine in leukaemia. 752 88

Using clonogenic assay we investigated the effect of stem cell factor (SCF) on the in vitro growth of clonogenic precursor cells from acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in the presence or absence of recombinant human erythropoietin (rhEpo) or recombinant human granulocyte colony-stimulating factor (rhG-CSF). SCF as a single factor did not induce significant colony formation, and even in the presence of rhEPO or rhG-CSF it very weakly stimulated erythroid colony formation and was rarely capable of inducing myeloid colony formation by clonogenic leukemic cells. In culture dishes supplemented with SCF, both myeloid and erythroid colony formations were dramatically enhanced in MDS, regarding both colony number and size. Colony-formation abilities by MDS progenitors were improved following costimulation with SCF and rhEpo. These results suggest that SCF may have a therapeutic role in restoring hematopoiesis in patients with MDS.
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PMID:Effect of stem cell factor (c-kit ligand) on clonogenic leukemic precursor cells: synergy with other hematopoietic growth factors. 752 82

Congenital neutropenias include a heterogenous group of diseases characterized by a decrease in circulating neutrophils. In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections. We report the effects of long-term safety of subcutaneous r-metHuG-CSF administration in 54 patients (congenital n = 44. cyclic n = 10) treated for 4-6 years. A sustained ANC response was seen in 40/44 severe congenital neutropenia patients and 10/10 cyclic neutropenia patients. Two patients required an increase of > 25% in dose to maintain a clinical response; one patient became refractory to therapy. A significant decrease in the incidence of severe infections and the need for intravenous antibiotics was noted. Significant adverse events noted which may or may not be related to therapy included: osteopenia (n = 15), splenomegaly (n = 12), hypersplenism (n = 1), vasculitis (n = 2), glomerulonephritis (n = 1), BM fibrosis (n = 2), MDS/leukaemia (n = 3), and transient inverted chromosome 5q with excess blasts (n = 1). R-metHuG-CSF has been well tolerated in the majority of patients and resulted in a long-term improvement in their clinical status.
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PMID:Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias. 1093 Oct 6

To evaluate the safety and efficacy of subcutaneous administration of recombinant human granulocyte colony-stimulating factor in the myelodysplastic syndromes (MDS), 20 patients were given a daily dose of 50 micrograms/m2 of KRN8601 for 4 weeks. When the blood neutrophil count did not reach 2,000/microliters within 2 weeks, the dose was increased to 100 micrograms/m2. A marked neutrophilic response was obtained in 17 of the 18 evaluable patients (94.4%), irrespective of the MDS disease type. Five patients showed a platelet increase, 3 of which also showed an erythroid improvement. To maintain neutrophil levels greater than 1,000/microliters, 12 patients were treated with KRN8601 for 4 weeks. A dose of 25 to 50 micrograms/m2 3-4 times a week served to this end in 8 patients and 100 micrograms/m2 three times a week or daily in the remaining 4 patients. One patient with RAEB progressed to acute myeloid leukemia 8 weeks after KRN8601. The treatment was well-tolerated in the majority of patients with no severe toxicities. These results suggest that subcutaneous administration of KRN8601 is safe and useful in the treatment of cytopenias in MDS.
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PMID:[A phase III trial of subcutaneous administration of rhG-CSF in the myelodysplastic syndromes]. 752 42

Myelodysplasia and acute myeloid leukaemia (MDS/AML) developed in three cases of severe aplastic anaemia (SAA) and one case of congenital neutropenia (CN, Kostmann's disease) who received recombinant human granulocyte colony-stimulating factor (G-CSF) are reported. In these four MDS/AML cases, age at diagnosis of SAA/CN was 0-13 years, the cumulative dose of G-CSF was 98 micrograms/kg to 10 mg/kg over 1-57 months, and the interval from initiation of G-CSF to MDS/AML was 25, 23, 31 and 57 months, respectively. These results suggest a link between SAA/CN and MDS/AML in relation to G-CSF administration; however, large studies are necessary to determine if such a risk is significant in patients with SAA/CN who are treated with G-CSF.
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PMID:Myelodysplasia and acute myeloid leukaemia in cases of aplastic anaemia and congenital neutropenia following G-CSF administration. 753 Apr 77


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