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

We report herein the case of a 61-year-old man with myelodysplastic syndrome causing pancytopenia who underwent successful coronary artery bypass grafting (CABG). Preoperatively, his hemoglobin (Hb) value was 10.4 g/dl while receiving transfusions of 1 or 2 units of red blood cells (RBC) every 2 weeks, his white blood cell (WBC) count was 8200/microliter with injections of 100 micrograms granulocyte colony-stimulating factor (G-SCF) every 5 days, and his platelet count was 4.5 x 10(4)/ microliter without platelet transfusion. From the time the pancytopenia was diagnosed in his peripheral blood, he had received a total of 104 units of RBC and 472 units of platelets, following which he developed an antiplatelet antibody, not for a platelet-specific antigen, but for an HLA antigen. Thus, HLA-matched platelets were prepared to prevent bleeding caused by thrombocytopenia, and the WBC count was elevated preoperatively by G-CSF injections. Thereafter, CABG was performed on three vessels. The HLA-matched platelets were transfused as the patient was weaned from the extracorporeal circulation. As a result of these preparations, we were able to protect the patient against bleeding and infection.
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PMID:Successful coronary artery bypass grafting for a patient with myelodysplastic syndrome: report of a case. 888 52

Ineffective hematopoiesis with associated cytopenias and potential evolution to acute myeloid leukemia (AML) characterize patients with myelodysplastic syndrome (MDS). We evaluated levels of apoptosis and of apoptosis-related oncoproteins (c-Myc, which enhances, and Bcl-2, which diminishes apoptosis) expressed within CD34+ and CD34- marrow cell populations of MDS patients (n = 24) to determine their potential roles in the abnormal hematopoiesis of this disorder. Marrow cells were permeabilized and CD34+ and CD34- cells were separately analyzed by FACS to detect: (1) a subdiploid (sub-G1) DNA population, and (2) expression of Bcl-2 and c-Myc oncoproteins. Within the CD34+ subset, a significantly increased percentage of cells demonstrated apoptotic/sub-G1 DNA content in early (ie. refractory anemia) MDS patients compared with normal individuals and AML patients (mean values: 9.1% > 2.1% > 1.2%). Correlated with these findings, the ratio of expression of c-Myc to Bcl-2 oncoproteins among CD34+ cells was significantly increased for MDS patients compared to those from normal and AML individuals (mean values: 1.6 > 1.2 > 0.9). Bcl-2 and c-Myc oncoprotein levels were maturation stage-dependent, with high levels expressed within CD34+ marrow cells, decreasing markedly with myeloid maturation. Treatment of seven MDS patients with the cytokines granulocyte colony-stimulating factor plus erythropoietin was associated with decreased levels of apoptosis within CD34+ marrow cells and may contribute to the enhanced hematopoiesis in vivo that was shown. These findings are consistent with the hypothesis that altered balance between cell-death (eg, c-Myc) and cell-survival (eg, Bcl-2) programs were associated with the increased degrees of apoptosis present in MDS hematopoietic precursors and may contribute to the ineffective hematopoiesis in this disorder, in contrast to decreased apoptosis and enhanced leukemic cell survival in AML.
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PMID:Altered oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells. 894 64

An 84-year-old woman was admitted with acute non-lymphoblastic leukemia transformed from myelodysplastic syndrome. We examined the signal transduction of the leukemic blasts. Stimulation of the blasts by macrophage colony-stimulating factor (M-CSF) resulted in tyrosine phosphorylation of several cellular proteins. In vitro proliferation of leukemic blasts was stimulated by M-CSF, but not by granulocyte colony-stimulating factor. Based upon these findings, combined therapy with M-CSF and low dose cytosine arabinoside (ara-C) was successful. After her recovery, we confirmed marked reduction of blasts and disappearance of M-CSF-responsive cells. These results suggest that M-CSF could enhance the cytotoxic effect of ara-C on leukemic blasts via its intracellular signaling pathway linked to proliferation.
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PMID:[Successful treatment of acute non-lymphoblastic leukemia from myelodysplastic syndrome by combination of human macrophage colony-stimulating factor (M-CSF) and low dose cytosine arabinoside: M-CSF-induced proliferation and tyrosine phosphorylation in leukemic blasts]. 896 Jun 58

Investigations of the effects of hematopoietic growth factors (HGFs) on the cell cycle of cells from myelodysplastic syndrome (MDS) have been hampered by technical difficulties. In this study, using a recently established flow cytometric method that enables detailed analysis of the cell cycle (Gzero-, G1-, S-, and G2/M-phases) of target cells in a heterogeneous cell population, we examined the effects of granulocyte colony-stimulating factor (G-CSF) and other HGFs on the cell cycle of CD13-positive cells (blasts and other malignant myelocytic and monocytic cells) in MDS. The cell cycle response to G-CSF (decrease in Gzero-phase cells and increase in S-phase cells) was heterogeneous among MDS cases. When the data for 13 MDS cases and 15 de novo AML cases were compared statistically, the magnitude of cell cycle activation by G-CSF was weaker for the cells from the MDS cases. Stem cell factor, interleukin-3, or a combination of these HGFs with G-CSF reduced the Gzero-phase cell percentage in all examined MDS cases whose cell cycle was unresponsive to G-CSF alone. When cytosine arabinoside was added to cells with or without stimulation by HGFs, the viable G0-phase cell count was reduced in HGF-stimulated cells compared with unstimulated cells in seven of eight cases. The present results suggest that G-CSF-induced cell cycle stimulation of malignant cells can be expected in a fraction of MDS patients and that even in MDS patients whose cells do not respond to G-CSF, employment of other HGFs and their combination with G-CSF is worth consideration. The results also suggest that a well-designed therapy using HGFs and chemotherapeutic drugs may reduce the quiescent (Gzero) cell count in MDS, which is assumed to be responsible for drug resistance derived from cell kinetics.
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PMID:Cell cycle modulation by hematopoietic growth factors in myelodysplastic syndromes: analysis by three-color flow cytometry. 898 1

Cytarabine ocfosfate (SPAC) was administered orally to 19 patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). SPAC was administered at doses of 200-300 mg/day for more than 14 days with granulocyte colony-stimulating factor (G-CSF). Four of the 12 patients with AML and 1 of the 7 patients with MDS achieved complete remission (CR) after one cycle of SPAC treatment. Especially, 3 of the 6 patients with newly diagnosed AML achieved CR. Major side effects of SPAC were myelosuppression and tolerable gastrointestinal disorders. The treatment with SPAC is a therapeutic option in elderly patients or patients with organ failure.
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PMID:Treatment of acute myeloid leukemia and myelodysplastic syndrome with orally administered cytarabine ocfosfate and granulocyte colony-stimulating factor. 911 97

The myelodysplastic syndromes (MDSs) are a group of haematological disorders found predominantly in the elderly, and are defined by morphological abnormalities of the three cell lines. None of the abnormalities is specific for MDS but, when combined with active or hyperactive haemopoiesis and refractory cytopenia in an elderly person, they suggest the diagnosis. The French-American-British co-operative group divided MDSs into five types: refractory anaemia; refractory anaemia with ring sideroblasts; refractory anaemia with excess of blasts; refractory anaemia with excess of blasts in transformation; and chronic myelomonocytic leukaemia. The classification was based on the number of blasts in the bone marrow, dysplastic features in one or more cell lines, ringed sideroblasts, blasts in the peripheral blood, Auer rods in the granulocyte precursors and absolute monocytosis. MDS can be a primary condition and of unknown aetiology or develop secondary to the action of a known agent such as an alkylating agent, chemical or recombinant human granulocyte colony-stimulating factor. The pathogenesis of MDS is thought to be a multi-step process which begins with a somatic mutation in the pluripotential stem cell, is irreversibly altered and acquires a survival advantage. The abnormal clone expands at the expense of normal haemopoiesis and undergoes further genetic change to give a progressively more malignant phenotype. Present theories of the development of MDS are speculative but further research could cast light on the development of other haematological disorders.
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PMID:The myelodysplastic syndromes. 916 9

Granulocyte colony-stimulating factor (G-CSF) has been used to improve granulocyte count in chronic neutropenia and myelodysplasia, to minimize the incidence and duration of neutropenia during conventional chemotherapy, and to mobilize peripheral blood stem cells prior to leukapheresis for use in autologous and allogeneic marrow transplantation. The most common toxicity is bone pain, and other reactions such as inflammation at the site of injection have also occurred. In patients with chronic neutropenia, splenomegaly has been described with long-term use, and extramedullary hematopoiesis has also been reported. However, thus far, no life-threatening sequelae of these effects are found in the literature. We now describe a case of spontaneous splenic rupture four days following a six-day course of G-CSF therapy in an allogeneic donor of peripheral blood stem cells.
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PMID:Spontaneous splenic rupture following administration of granulocyte colony-stimulating factor (G-CSF): occurrence in an allogeneic donor of peripheral blood stem cells. 950 2

When a new product with huge clinical potential explodes on the scene, the hope is that the benefits far outweigh the risks in long-term administration. After 10 years of clinical use, granulocyte colony-stimulating factor (G-CSF) has lived up to that promise so far. In the context of severe chronic neutropenia, more than 90% of patients have reaped big benefits in terms of improved quality of life and less infection, inflammation, antibiotic use, and hospitalization as well as oropharyngeal ulcers. With long-term use, toxic and adverse events have been catalogued but in general are not clinically troublesome and, aside from occasional adjustment of scheduling and dosing, seldom necessitate stopping therapy. Currently, the topic of intense focus is the phenomenon of malignant myeloid transformation in patients with congenital neutropenia who are receiving G-CSF. Data from the Severe Chronic Neutropenia International Registry have identified 23 of 249 patients with congenital neutropenia who have developed myelodysplasia or acute myelogenous leukemia (MDS/AML) giving a crude rate of about 9% with an average follow-up of 4.5 years. No cases of MDS/AML have occurred in 257 patients with cyclic or idiopathic neutropenia. A critical analysis of the incidence of transformation year by year showed a fairly uniform hazard rate of less than 2% per year, and the risk of MDS/AML after 5 to 6 years of therapy did not appear to be greater than during the first year of therapy. The transformation risk in the congenital cohort must also be viewed in the context of published reports of spontaneous myelodysplasia or acute myelogenous leukemia occurring in these patients in the pre-G-CSF era. Thus, the role of G-CSF in malignant conversion is still not clear and requires long-term vigilance and research. G-CSF is still deemed specific therapy for severe chronic neutropenia with a high margin of safety and should be the initial treatment for this family of disorders.
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PMID:Safety of long-term administration of granulocyte colony-stimulating factor for severe chronic neutropenia. 920 40

A study of bone marrow morphology and apoptosis was undertaken in 51 patients with myelodysplastic syndromes (MDS) treated with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO). In 19 of these patients (37%), a significant improvement in the hemoglobin level was found after treatment. Apoptosis was measured using a nick-end labeling (TUNEL) technique. Patients with MDS had a significantly higher percentage of labelled (apoptotic) cells in the bone marrow compared to healthy individuals (56.3 +/- 3.8% vs. 16.2 +/- 1.4%, p = 0.0001). Patients with RAS showed a lower percentage of apoptotic cells than patients with RA (68.5 +/- 9% vs. 46.5 +/- 4.8%, p < 0.05), while patients with RAEB did not differ significantly from either RA or RAS. In the patients who responded to treatment, the bone marrow samples displayed significant morphological changes. The percentages of erythroid precursors and myeloblasts were reduced after treatment, and patients who had ring sideroblasts before treatment also showed a reduction in the percentage of these cells. Total erythroid index also decreased in responding patients. The percentage of apoptotic cells decreased significantly in responding patients (58.8 +/- 4.8% before treatment vs. 44.5 +/- 5.5% after treatment, mean reduction 18.3%, p = 0.0003), whereas no significant change was found in non-responding patients. Our results suggest that one important mechanism behind the positive effects of treatment with G-CSF and EPO is a reduction in the degree of ineffective hematopoiesis in MDS.
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PMID:Morphological changes and apoptosis in bone marrow from patients with myelodysplastic syndromes treated with granulocyte-CSF and erythropoietin. 922 70

Humoral regulation of granulocytopoiesis was proven 30 years ago by discovery of factors which stimulate production of granulocyte colonies (CSF-colony stimulating factors), while clinical utilization of recombinant human colony stimulating factors (rhGM-CSF and rh-CSF) is present for the last 10 years. On the basis of this, today we have a lot of experience in regard to indications, modes and results of their clinical utilization. Clinical utilization of CSF is divided into three fields: treatment of the neutropenic syndrome, utilization in oncologic patients and in bone marrow transplantation. The best results have been achieved in neutropenic syndrome therapy, both chronic (congenital, cyclic and idiopathic neutropenia, aplastic anemia and myelodysplastic syndrome) and acute (granulocytopenia drug induced, postirradiation neutropenia). In oncologic patients it is used to eliminate neutropenia which occurs after cytostatic therapy with standard doses or high dose cytostatic therapy with better effects on the tumor, but with myeloablation. Granulocyte colony-stimulating factor is also used for stimulating fast granulocytopoiesis in autologous or allogeneic bone marrow transplantation, in unsatisfactory transplants especially. In recent years it has been used for mobilization of progenitor CD34+ cells in the donor in order to perform their transplantation, especially in treatment of chronic myeloid leukemia. At our institution G-CSF has been successfully used in 17 patients.
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PMID:[Clinical use of granulocyte colony stimulating-factors (GM-CSF and G-CSF]. 922 90


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