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

Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a polypeptide hormone produced through recombinant DNA technologies in glycosylated (yeast or mammalian expression systems) or nonglycosylated (Escherichia coli expression system) form. It is a multilineage haematopoietin which stimulates proliferation and differentiation of bone marrow myeloid progenitors and increases peripheral white blood cell counts when administered systemically. Treatment is generally well tolerated, although mild to moderate flu-like symptoms are common and rGM-CSF-induced fever and fluid retention may be problematic in occasional patients. rGM-CSF accelerates recovery of peripheral neutrophil counts after bone marrow transplantation, and results of a placebo-controlled randomised trial correlate this with reduced infectious episodes and shortened length of hospitalisation in patients with lymphoid malignancies. A substantial number of patients with graft failure after bone marrow transplantation also respond to rGM-CSF. The duration of myelosuppression secondary to cancer chemotherapy can be significantly reduced by rGM-CSF which has permitted investigation of antineoplastic dose-intensity escalation. In some haematopoietic disorders (e.g. aplastic anaemia, myelodysplasia and neutropenia secondary to HIV infection and antiviral therapy), rGM-CSF produces clinically useful increases in peripheral blood granulocyte counts, although the effect is generally not sustained after drug withdrawal. The potential for rGM-CSF to stimulate proliferation of the abnormal clone in myelodysplasia and in acute myelogenous leukaemia following induction therapy is of concern. Available data suggest, however, that with appropriate monitoring and exclusion of high-risk patients this serious potential risk can be avoided, and that myelopoiesis is enhanced in such patients by rGM-CSF treatment. Recombinant colony-stimulating factors are a new therapeutic modality; hence many aspects of their use remain to be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has major potential in the management of myelosuppression secondary to cytoreductive therapy with or without bone marrow transplantation, and in amelioration of disturbed myelopoiesis. It represents an important application of biotechnology to a difficult area of therapeutics.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). A review of its pharmacological properties and prospective role in the management of myelosuppression. 137 18

In 25 patients (22 males, 3 females--median age 39 years) with AIDS (CDC stages IV A-D) and no preceding myelotoxic therapy, morphometry and immunohistochemistry (CD 61-Y 2/51) was performed on trephine biopsies of the bone marrow to evaluate the megakaryocytic lineage. In comparison with megakaryocytes in the myelodysplastic syndromes (MDS) significant differences were evident. In AIDS this cell population revealed a size distribution within the normal range (control group) and no predominance of micromegakaryocytes characteristic for MDS. Furthermore, by determination of the form factors more irregular shapes of cell and nuclear perimeters could be shown. Finally, a not-evaluated number of precursors (promegakaryoblasts) was calculable. Particularly in those patients (n = 15) with AIDS-related severe thrombocytopenia the missing increase in the relative amount of promegakaryoblasts was conspicuous. This result was strikingly different from findings in idiopathic (autoimmune) thrombocytopenia and suggested an impairment of progenitor cell proliferation and differentiation in the acquired immunodeficiency syndrome. In conclusion, morphometry in combination with immunohistochemistry failed to establish characteristic myelodysplastic aspects of the megakaryocytic lineage in AIDS. For this reason, bone marrow lesions in this disorder should be properly termed HIV-myelopathy and not myelodysplasia.
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PMID:Megakaryocytopoiesis in bone marrow biopsies of patients with acquired immunodeficiency syndrome (AIDS). An immunohistochemical and morphometric evaluation with special emphasis on myelodysplastic features and precursor cells. 143 34

We have isolated a lymphoid cell line, MDS, from the pleural exudate of a patient with chronic myelomonocytic leukemia. The cells are biphenotypic, containing various T-cell and myeloid markers, and are surface negative for CD4 and CD8 but have low CD4 mRNA. The cells grow in suspension with a doubling time of 15 hr, have been karyotyped as trisomy 21, are negative for human immunodeficiency virus type 1 (HIV-1), and are tumorigenic in the nude mouse. We have isolated two stable HIV-1-producing cell lines, MDS-T, by transfecting MDS cells with pHXBc2, and MDS-I, by infecting MDS cells with HIV-1IIIB. In 24 hr, 1 x 10(5) MDS-T or MDS-I cells produce 46 ng of p24 per ml and reverse transcriptase that is capable of incorporating 0.2 pmol of [32P]TTP into oligo(dT).poly(A). Ultrastructural studies showed numerous mature viral particles in MDS-T and MDS-I cells that are capable of infecting T cells. HIV-1 infection could be inhibited by 25% in the MDS cells with the anti-CD4 antibody Leu 3a. For over a year MDS-T and MDS-I cells have been producing high concentrations of HIV-1 in culture. A subclone derived from the MDS cells behaves like the parent cells when transfected or infected with HIV-1. In contrast to other T-cell lines, neither phorbol 12-myristate 13-acetate nor tumor necrosis factor alpha stimulated the replication of HIV-1, whereas bromoadenosine 3',5'-cyclic monophosphate or interferon alpha caused 50% and 80% inhibition of reverse transcriptase production, respectively. These chronically infected T-cell lines are a useful model system to study the effect of anti-HIV agents and cellular factors required for HIV-1 replication.
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PMID:Productive nonlytic human immunodeficiency virus type 1 replication in a newly established human leukemia cell line. 143 50

Bone marrow biopsies from 125 patients at different stages of HIV infection were examined and the histopathological changes are described. Indications for biopsy included peripheral blood abnormalities, search for opportunistic pathogens, a suspected lymphoma or evaluation of its progression. Common histopathological features, suggestive of HIV infection but non-pathognomonic, were: severe hypercellularity (43.2%), myelodysplasia (74.4%), plasmocytosis (86.4%), and lymphocytic (36.8%) and histiocytic infiltrates with or without granulomas (20%). Reticular fibrosis (58.6%), iron deposits (59.2%), vascular congestion and mucoid degeneration of fat (18.4%) were frequently observed. Hypoplasia was usually a late-occurring event and/or may have been iatrogenic. Opportunistic infections were detected in 8 patients: Mycobacterium avium intracellulare (4 cases), Mycobacterium tuberculosis (1 case), Cryptococcus neoformans (1 case), and Leishmania (1 case). Neoplastic complications were found in 3 patients: Burkitt's lymphoma (1 case) and Hodgkin's disease (2 cases). The pathophysiological mechanisms envisaged include the effect of HIV infection on precursor cells in the bone marrow.
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PMID:[The bone marrow in human HIV infection. A bioptic study of 125 cases]. 152 53

Recombinant human colony-stimulating factors (CSFs) have potential for wide use in the areas of oncology and infectious disease. Granulocyte CSF and granulocyte-macrophage CSF currently are approved for use in the treatment of neutropenia associated with standard-dose cancer chemotherapy and bone marrow transplantation, respectively. Other settings in which these agents have shown promise are dose-intensive chemotherapy, enhancement of progenitor cell support, primary and acquired neutropenias, myelodysplasia, aplastic anemia, and cytopenias associated with human immunodeficiency virus infection or myelosuppressive therapies for such infection or related conditions. Clinical findings in these areas are encouraging, and potential exists for additional applications of the CSFs.
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PMID:Colony-stimulating factors: clinical applications. 159 11

Hematologic manifestations of human immunodeficiency virus (HIV) infection include cytopenias, non-Hodgkin's lymphoma, and myelodysplasia. Acute lymphocytic leukemia has rarely been reported in association with HIV infection. We describe a patient who presented with Burkitt cell leukemia and myelodysplasia as her initial manifestation of HIV infection. The dysplastic features included circulating asymmetric binucleated red blood cells as well as pseudo Pelger-Huet cells. To the best of our knowledge, this has not been previously reported.
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PMID:Burkitt cell leukemia with myelodysplasia as a presentation of HIV infection. 160 45

Oral hairy leukoplakia (OHL) has been observed in all risk groups seropositive for HIV infection. Recently, this lesion has also been described in HIV-seronegative patients with immunosuppression of iatrogenic origin. We report on a HIV-1 and HIV-2 seronegative, heterosexual man affected by refractory anemia with ringed sideroblasts (myelodysplastic syndrome), who developed recurrent oral condylomata acuminata and OHL as an early clinical manifestation. The diagnosis of OHL was confirmed by identifying Epstein-Barr viral particles by electron microscopy and by in situ DNA hybridization. HIV infection was ruled out using polymerase chain reaction and testing for HIV-1 and HIV-2 antibodies.
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PMID:Recurrent oral condylomata acuminata and hairy leukoplakia: an early sign of myelodysplastic syndrome in an HIV-seronegative patient. 165 14

To determine the true incidence of abnormalities in bone marrow specimens from patients infected with human immunodeficiency virus (HIV) and the clinical significance of these abnormalities regarding their cause and their role in the production of hematologic complications, 216 bone marrow biopsies, aspirates, and/or imprint preparations from 178 patients who either were seropositive for HIV infection or met the Centers for Disease Control (CDC) criteria for acquired immunodeficiency syndrome (AIDS) were studied. Detailed morphologic review was performed in a blind fashion as to clinical status. Extensive clinical, therapeutic, and laboratory data were collected for each patient. Statistical analysis was performed to detect significant correlations between morphologic findings and clinical/therapeutic/laboratory features. Among the most common bone marrow findings were hypercellularity (53% of specimens), myelodysplasia (69%), evidence of reticuloendothelial (RE) iron blockade (65%), megaloblastic hematopoiesis (38%), fibrosis (20%), plasmacytosis (25%), lymphocytic aggregates (36%), and granulomas (13%). A number of statistically significant correlations between morphologic findings and clinical features were noted. No significant association was detected between any morphologic finding and therapy with a variety of drugs. In 7 of 14 (50%) patients found to have marrow involvement by malignant neoplasm, the bone marrow represented the initial site of diagnosis of the neoplasm. Most of the bone marrow abnormalities associated with HIV infection appear to be related directly to the infection or its complications and not to therapeutic intervention. In certain clinical situations, bone marrow examination continues to be useful in the management of patients infected with HIV.
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PMID:The bone marrow in human immunodeficiency virus (HIV)-related disease. Morphology and clinical correlation. 170 27

Bone marrow biopsies of 23 HIV-1 infected patients and 29 patients with myelodysplastic disorders were examined histologically by immuno- and enzyme-histochemical techniques and morphometrical methods. The nucleolar organizer regions (AgNOR) were demonstrated and visually counted. Hypercellularity in marrows of AIDS patients is substantially caused by an increase of erythropoiesis and CD68+ macrophages/reticular cells. However, hypercellularity in preleukemia results from hyperplasia of all hematological cell lines and CD68+ bone marrow macrophages/reticular cells. AgNOR count is positively correlated with granulo- and erythropoiesis in preleukemia. In AIDS there is such a positive correlation between AgNOR count and granulopoiesis whereas an inverse relationship appears in erythropoiesis. The results suggest that HIV-associated bone marrow alterations differ from merely reactive changes and are related to myelodysplastic disorders.
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PMID:[Comparison of HIV-associated dyshemopoiesis in myelodysplastic HIV-negative patients]. 170 74

An immunomorphometric study was performed on formalin-fixed and paraffin-embedded bone marrow biopsies in 20 patients with AIDS (18 males, 2 females-stage IV A-D). In comparison with a control group megakaryocytes (CD61-Y2/51) revealed not only a significant hyperplasia, but remarkably irregular shapes of cells and nuclei, together with a disturbance of the nuclear-cytoplasmic ratio. No predominance of micromegakaryocytes as in myelodysplastic syndromes was observable. Contrasting idiopathic (immune)-thrombocytopenia, HIV-infected patients with a pronounced depression of the platelet count did not show a significant elevation of the number of promegakaryoblasts. This feature is in keeping with findings of a severe impairment of progenitor cell proliferation and differentiation in AIDS. There was a pronounced increase in the macrophage population (PG-M1). This alteration may be related to inflammatory lesions accompanying this disorder as well as to an enforced and premature destruction of hematopoietic cell elements in the myeloid stroma.
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PMID:[Immunohistochemistry and morphometry of bone marrow in acquired immunodeficiency syndrome with special emphasis on megakaryopoiesis and macrophages]. 172 14


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