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

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

In conclusion, hematopoietic growth factors have been shown to enhance the recovery and function of circulating WBCs after standard-dose cancer therapy or high-dose cancer therapy with ABMT, and preliminary data strongly suggests that these agents may have the ability to restore leukocyte numbers and competence in AIDS, myelodysplastic syndromes, and other marrow failure states. Phase I and II trials of GM-CSF in patients with AIDS, cancer, marrow failure states, and following bone marrow transplantation have been published, and limited phase III randomized trial experiences have been reported as well. Overall, GM-CSF represents a fascinating molecule with which to modulate human hematopoiesis in vivo. The multilineage stimulatory effects of GM-CSF that are evident in vitro have not been striking or consistent in clinical trials. However, the effects of GM-CSF on the production and function of mature neutrophils, monocytes, and eosinophils have been noted in the vast majority of clinical scenarios in which this cytokine has been tested. The clinical benefits of GM-CSF have, to date, only been proven in large-scale randomized studies of recovery from ABMT for lymphoid neoplasms. However, further data regarding the use of GM-CSF in other clinical settings have been generated, and the final results are eagerly anticipated by the oncology community. The beneficial effects of GM-CSF following ABMT consisted not only of a shorter period of absolute neutropenia, but also fewer significant infections, a diminished requirement for intravenous antibiotic administration, and a shorter overall duration of inpatient hospitalization. The use of GM-CSF in clonal disorders of hematopoiesis, such as myelodysplasia or myeloid leukemias, requires caution before such applications can be routinely recommended, and the demonstration of safety in this setting from large randomized trials will be needed. Preliminary data from small randomized trials suggests that the incidence of evolution to leukemia in patients with myelodysplasia and the number of patients with regrowth of leukemia after induction treatment in relapsed patients with AML may not be significantly different than in patients who do not receive GM-CSF. Various neutropenic conditions (eg, idiopathic or congenital) may respond clinically to hematopoietic growth factors such as GM-CSF. Patients treated for 3 to 15 months continue to respond with significantly increased granulocytes and resolution of prior infection. The subcutaneous route of administration is convenient and patients seem to accept it readily. It is difficult to determine the extent to which adjunctive therapy with GM-CSF will be cost effective.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF): preclinical and clinical investigations. 150 75

58 death certifications (40 males and 18 females) of residents of the Canton of Vaud (Switzerland) which reported AIDS as the cause of death in 1986-1989 were matched with the list of incident cancers available since 1974 from the Vaud Cancer Registry. Such linkage was successful for 20 individuals (age range 25-63, median 37), mostly males (18/20), homosexual or bisexual (11/18) and affected by Kaposi's sarcoma (14 males and 1 female). Other identified neoplasms included one Burkitt's lymphoma, one prostate adenocarcinoma and one multiple myeloma (whose histological picture included, however, lymphocytosis in addition to plasmocytosis). Three additional malignancies (one undifferentiated skin cancer, one carcinoma of the salivary glands and one in situ cervical carcinoma), and one myelodysplastic syndrome had also been diagnosed from 1 to 2 years before AIDS death. Cancer was mentioned on the death certificate, in addition to AIDS, in only 2 cases. Albeit of limited size, the present report confirms that a systematic integration of AIDS and cancer registration statistics provides additional information, of particular interest for histological classification, on the AIDS-cancer relationship.
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PMID:Linkage of death certification of AIDS and cancer registration in Vaud, Switzerland. 151 73

The terminal phase of the megakaryocyte life span is characterized by the onset of apoptosis to form compact, denuded megakaryocyte nuclei (DMK) surrounded by a thin rim of cytoplasm. Increased numbers of DMK have been reported in patients with acquired immune deficiency syndrome (AIDS) and chronic myeloproliferative disorders. In this study the bone marrow biopsies of 20 patients with various FAB subtypes of myelodysplastic syndrome (MDS) were examined for the presence of DMK cells and semiquantified for marrow reticulin level. For all MDS subtypes, a 9% or greater incidence of DMK in the total megakaryocyte population of the bone marrow was associated with a significant deposit of reticulin in the marrow. Immunocytochemical staining for Factor VIII (Von Willebrand factor), showed the abnormal deposition of this megakaryocyte protein in the extravascular stroma around many of the DMK cells. These findings are consistent with a hypothesis for excess stromal reticulin based on the defective maturation and intramedullary death of large numbers of megakaryocytes. The number of DMK in the marrow biopsies of MDS patients may have prognostic significance.
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PMID:Apoptotic megakaryocyte dysplasia in the myelodysplastic syndromes. 160 44

Colony stimulating factors (CSF) for white blood cells are formed in the bone-marrow and regulate proliferation and differentiation of the myeloid cells. Several of these hormones are cloned and manufactured by a recombinant technique for clinical use. The granulocyte-macrophage-colony-stimulating factor (GM-CSF) and the granulocyte-colony-stimulating factor (G-CSF) both belong to this group. Trials are still at the commencing stage. In vitro investigations, animal experiments and human experiments have rendered promising results. After intensive chemotherapy followed by treatment with GM-CSF and G-CSF, it has been demonstrated that the period of neutropenia following bone-marrow suppression is abbreviated. Accelerated bone-marrow regeneration and reduced tendencies to infection have been demonstrated compared with so-called control patients. In patients with the myelodysplastic syndrome, marked increase in the neutrophile granulocytes in the peripheral blood has been observed during treatment with growth factors. Long-term treatment with G-CSF has proved particularly effective in chronic idiopathic and cyclic neutropenia. On the other hand, the growth factors can scarcely improve the prognosis in severe aplastic anaemia. Animal experiments and a single human trial suggest that G-CSF and GM-CSF treatment are indicated in bone-marrow insufficiency secondary to radioactive irradiation accidents. GM-CSF has normalized the leucocyte counts in AIDS patients with leucopenia without any marked alteration in the tendency to infection. Future studies will show whether simultaneous treatment with growth factors and anti-viral and anti-leukaemic treatments, respectively, can improve the therapeutic results.
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PMID:[Myeloid hemopoietic growth factors. Therapeutic possibilities and clinical experiences]. 170 May 24

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

Granulocyte colony stimulating factor (G-CSF) can safely stimulate the production of neutrophils in normal and neutropenic patients. Phase II studies have shown potential benefit when G-CSF is given after chemotherapy and bone marrow transplantation and in dose intensification studies. Studies in myelodysplasia, chronic neutropenia and AIDS all show great promise. Phase III studies are now in progress, which will help identify precisely the role of this exciting molecule.
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PMID:Clinical studies of granulocyte colony stimulating factor (G-CSF). 170 54

Hematopoietic growth factors have now been purified, cloned, and produced in bacteria and yeast. Those that are currently in clinical study include erythropoietin, GM-CSF, G-CSF, M-CSF (also called CSF-1), and multi-CSF (also called interleukin 3). Growth factor appear likely to enhance the recovery and function of circulating white cells after standard-dose cancer therapy and high-bone-dose cancer therapy with marrow transplant and to restore leukocyte numbers and competence in the acquired immune deficiency syndromes and myelodysplastic syndromes. Phase I, II trials in AIDS, in cancer patients receiving chemotherapy, in cases of myeloproliferative disease, and after bone marrow transplant have been published. The results of phase III studies are just becoming available.
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PMID:G-CSF and GM-CSF in clinical trials. 170 37

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

Leukopenia or pancytopenia as a result of bone marrow dysfunction are manifestations of various diseases or complications of therapeutic regimens. The spectrum of diseases associated with leukopenia is wide and includes congenital as well as acquired neutropenias secondary to conditions such as myelodysplastic syndromes, AIDS, malignant tumors with or without chemotherapy-enhanced neutropenia, bone marrow transplantation or therapeutic or accidental radiation. The morbidity and mortality of infectious diseases is greatly enhanced during neutropenic phases. Over the last few years attempts have been made to shorten the duration and lessen the severity of neutropenia in patients with the above conditions by administration of Granulocyte Macrophage Colony Stimulating Factor (G-CSF). Both cytokines were successfully tested in phase I and II trials. Treatment with GM-CSF or G-CSF results in a dose-dependent increase of the neutrophil count. GM-CSF also increases the number of eosinophils and monocytes in peripheral blood. The effect of both cytokines on the neutrophil count is transient as long as the underlying disease persists. This prompted the institution of maintenance therapy, which has been successfully used with either cytokine. Long-term treatment is usually well tolerated and results in a reduction in the frequency of infections as well as in the duration of antibiotic treatments. Side effects of GM-CSF or G-CSF are usually mild and include fever, myalgia, bone pain, and erythema. A number of patients developed dyspnea, hypotension, sweating, flushing and erythema after the first dose of GM-CSF in each treatment cycle. This first-dose reaction occurs more frequently after intravenous than reactions were reported with G-CSF. Some patients with myelodysplastic syndrome progressed to acute myeloic leukemia during or after treatment with GM-CSF or G-CSF. Most of these patients presented with an increased fraction of blasts in the bone marrow, which preceded the treatment with the colony stimulating factors. Since GM-CSF and possibly G-CSF may increase the risk of developing acute leukemia in patients with myelodysplastic syndrome, it appears prudent to limit the use of these cytokines in patients with this disease. The subcutaneous route of administration appears to be preferable to intravenous administration, since the incidence and severity of side effects are reduced. While many questions concerning dosage, long-term therapy and combination therapy still remain unanswered, the information presented in this review concerning the clinical use of these cytokines warrants an optimistic outlook.
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PMID:[GM-CSF and G-CSF: cytokines in clinical application]. 170 94


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