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

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 70-year-old man was admitted to our hospital with pancytopenia. He was diagnosed as having MDS (RA), and therapy with subcutaneous S-CSF (100 micrograms/day) was started. His leukocyte count increased from 800/microliters to 1,400/microliters in two weeks. The dose of G-CSF was raised to 200 micrograms/day in the third week, and leukocytes increased to 2,00/microliters. At the fifth week, intravenous EPO (6,000 U x 3 times/week) was added. His leukocyte count increased to 4,000/microliters. EPO therapy was raised to 12,000 U x 3 times/week at the eighth week, his leukocyte count remained at the same level. G-CSF and EPO was stopped at the eleventh week, and leukocytes decreased to the same level as before administration. Throughout the course, his platelet count and reticulocyte count did not change. G-CSF and EPO are known as the stimulators of granuriod and erythroid progenitor, respectively. However, in this case, combination therapy with G-CSF and EPO induced marked increase of granulocytes only. This was an interesting case in relation to the roles of these cytokines in the hematopoietic system.
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PMID:[Combination therapy with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) induced prominent granulocyte increase in an elderly case of myelodysplastic syndrome (MDS)]. 768 8

Severe congenital neutropenia is a disorder of myelopoiesis characterized by severe neutropenia secondary to either a maturational arrest of myelopoiesis at the level of promyelocytes (Kostmann-Syndrome; SCN) or regular cyclic fluctuations in the number of blood neutrophils with a median ANC below 500/microliter (cyclic neutropenia). We have treated 32 patients with SCN and 4 patients with cyclic neutropenia. Thirty of 32 patients with SCN and all 4 patients with SCN responded to r-met HuG-CSF treatment with an increase of the median ANC to above 1000/microliter. The doses needed to achieve and maintain the response varied between 0.8 and 120 micrograms/kg/d. Long-term treatment did not exhaust the myelopoiesis: The mean ANC remained stable up to 5 years of treatment. The increase in ANC was associated with dramatic clinical responses: significant reduction of severe bacterial infections, reduction of intravenous antibiotic treatment episodes, and reduction of hospitalizations. No severe bacterial infections occurred in any of the r-met HuG-CSF responders during long-term treatment. Severe adverse event, most likely associated with the underlying disease, included the development of MDS/Leukemia in two patients, and osteopenia/osteoporosis in 12 patients. These results demonstrate the beneficial effects of r-met HuG-CSF treatment in severe congenital neutropenia patients.
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PMID:[Long-term treatment with recombinant human granulocyte colony stimulating factor in patients with severe congenital neutropenia]. 769 Aug 65

Severe chronic neutropenia (SCN) is a rare but important cause of recurrent fevers, oropharyngeal ulcerations and severe infections. In three forms of SCN, i.e., congenital neutropenia (Kostmann's syndrome and related syndromes), idiopathic neutropenia (both childhood and adult), and cyclic neutropenia, it is now established that long-term treatment with the hematopoietic growth factor, recombinant human granulocyte colony stimulating factor (rHuG-CSF or Filgrastim), can elevate blood neutrophil counts to the normal range in most patients, with a concomitant reduction in infection-related events including fever, oral ulcerations, antibiotic use and symptoms of inflammation. Treatment with this growth factor causes an increase in the number and maturity of marrow cells of the neutrophilic series; other cell lines are largely unaffected. Marrow stimulation and expansion are reflected by the occurrence of bone pain early in therapy, as well as some increase in spleen size in most cases. Adverse effects of therapy are infrequent in both children and adults, and long-term treatment with daily or every-other-day s.c. injections of rHuG-CSF are well accepted. Because of the risk that some patients with chronic neutropenia may have or develop myelodysplasia and/or leukemia, careful pretreatment evaluations (blood, bone marrow and cytogenetics) and long-term observations are extremely important. An international registry for patients with SCN has been established to maintain records and further investigate these conditions.
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PMID:Hematopoietic growth factors for the treatment of severe chronic neutropenia. 778 81

Acute myeloid leukemia preceded by a myelodysplastic syndrome (MDS-AML) is generally regarded as a high-risk type of AML, where remissions are rare and of short duration. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is suggested to increase the sensitivity of leukemic cells to cycle-specific drugs. In this study 14 MDS-AML patients were given rhGM-CSF together with standard induction chemotherapy (TAD). rhGM-CSF was started 48 h prior to chemotherapy and given for up to 3 weeks. The results showed eight (58%) complete and two (14%) partial remissions, while another two (14%) patients had minor responses. One patient relapsed after 1 year, and then responded a second time. rhGM-CSF had to be stopped owing to local allergic reactions in two patients, both non-responders, but was otherwise well tolerated. Compared with our historical group of controls we found significantly higher remission rates, fewer early deaths, fewer fever days, and fewer days with both neutropenia and thrombocytopenia among the patients treated with rhGM-CSF and TAD. The estimated median over-all survival was 332 days. The severity of initial myelodysplastic changes did not correlate to the outcome of therapy but the degree of peripheral blood dysplasia decreased among responding patients. MDS-AML patients in this pilot study did respond better, and with minimal toxicity, when standard induction chemotherapy was given in combination with rhGM-CSF.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in acute myeloid leukemia evolving from myelodysplastic syndromes: a pilot study. 793 58

Granulocyte, macrophage colony stimulating factor (GM-CSF) and granulocyte--colony--stimulating factor (G-CSF) are two of the growing number of recognized cytokines involved in the regulation of hematopoiesis. The purification of these factors and the subsequent cloning of the DNAs which encode these proteins have led to their widespread clinical use in the setting up of therapy of disease-induced myelosuppression. GM-CSF has a broader spectrum of potential targets than G-CSF and promotes growth of progenitors of several myeloid lines and, to a lesser extent, of the megakaryocyte line. The pleiotropic effects of GM-CSF could therefore, theoretically, be an advantage compared with the more restricted activity of G-CSF. Its greatest potential use appears to be in the amelioration of neutropenia following myelosuppressive therapy. GM-CSF has demonstrated efficacy in decreasing the duration of neutropenia, decreasing the attendant infection, and enhancing the ability to deliver full doses of myelosuppressive therapy. GM-CSF can also reverse the neutropenia of myelodysplastic syndrome and aplastic anemia. It enhances recovery from bone marrow transplantation and thus reduce the attendant morbidity of this procedure. This hematopoietic growth factor may also enhance recruitment and harvest to peripheral stem cells. At clinically usefull dosages GM-CSF is generally well tolerated.
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PMID:[Biology and clinical applications of GM-CSF]. 806 93

This case report concerns a woman thought to have a low blood count myelodysplastic syndrome who responded poorly to cytosine arabinoside. She was treated with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and had an adverse reaction resembling a capillary leak syndrome. Later on, an episode of post-transfusion hemoglobinuria led to the correct diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). This case report suggests an adverse effect of GM-CSF on PNH.
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PMID:The effect of granulocyte-macrophage colony stimulating factor on paroxysmal nocturnal hemoglobinuria: a case report. 810 93

A 72-year-old male suffering with MDS was admitted to our hospital because of slowly progressive dementia, convulsions and consciousness disturbance. A CT scan of the brain showed a low density area in the right temporal to parietal lobe and T2-weighted MRI of the brain revealed a high intensity signal in the same area. Herpes simplex virus DNA was detected in CSF by PCR method. He was diagnosed as having herpes simplex encephalitis but his clinical course was prolonged and considered atypical as herpetic infection in CNS. However, after administration of aciclovir, progression of his symptoms stopped, and a CT scan still revealed abnormal findings with the same area after more than four months. We thought his chronic course of herpes encephalitis was caused by incomplete immune function suppressed by MDS.
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PMID:[A case of chronic herpes encephalitis with myelodysplastic syndrome (MDS)]. 820 Jan 42

As phase II study, we treated 18 patients with myelodysplastic syndrome (MDS) and 37 patients with aplastic anemia (AA) with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 14-28 days. Administration of rhGM-CSF resulted in a dose-dependent increase in circulating granulocyte counts, which was statistically significant in patients with AA. There were no consistent changes in monocyte and lymphocyte counts. Although no increase in both thrombocyte and erythrocyte counts was detected in the majority of the patients, a response of both lineages to rhGM-CSF, in addition to granulocyte lineage, was observed in 3 patients. Drug-associated adverse events developed in 28 patients (51%). The most frequent adverse event was fever. In general, the treatment with rhGM-CSF was well tolerated. The results suggest that rhGM-CSF is effective for patients with MDS and AA.
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PMID:Phase II study of recombinant human granulocyte-macrophage colony-stimulating factor in myelodysplastic syndrome and aplastic anemia. 821 99


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