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

Cytogenetic and bone marrow culture studies were performed sequentially in 13 patients with myelodysplastic syndromes (MDS) who responded to low dose cytosine arabinoside (Ara-C) treatment (complete in nine and partial in four patients). Of nine patients with initial clonal karyotypic abnormalities, six recovered a normal karyotype after attaining a response to treatment, but the other three patients retained partial or total karyotypic abnormalities. A new clonal karyotypic abnormality appeared after treatment in one patient. Eight patients showed normal colony growth of both granulocyte-macrophage colony-forming units and erythroid burst-forming units after treatment, but five were still defective. There was a clear difference in the duration of response to treatment between these two groups. Consolidation treatment was not effective in patients with persistent karyotypic abnormalities or defective colony formation. Although the number of patients studied is small, these results suggest that hemopoiesis in patients with MDS following a response to treatment with low dose Ara-C is heterogeneous. Consolidation chemotherapy is recommended to ensure and prolong the response in patients showing normalization of both cytogenetic and bone marrow culture results.
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PMID:Cytogenetic and clonal culture evaluation after response to low dose Ara-C in myelodysplastic syndromes. 196 Oct 37

Despite major advances in supportive care, neutropenic infections and thrombopenic bleedings remain major lethal treatment- and disease-related complications in patients with malignancy. Moreover, complications of platelet (Plt) and erythrocyte transfusion therapy have become a cause of great concern and shortages of homologous blood products are a constant problem. Suggestions that the application of recombinant human hemopoietins may provide an alternative treatment modality in this patient population is currently being evaluated in clinical trials. Erythropoietin (EPO) has been shown to be effective in the treatment of anemia in patients with bone marrow, infiltrating low-grade non-Hodgkin's lymphoma, multiple myeloma, and in some patients with myelodysplastic syndrome. Preliminary data suggest that subcutaneous administration of EPO results in a higher slope of increasing erythropoietic parameters compared to intravenous administration. Protective effects on normal erythropoiesis have been attributed to EPO in patients receiving chemotherapy. The finding of EPO receptors on megakaryocytes supports the clinical observation of increased Plt production associated with decreased bleeding and transfusion frequencies in a substantial number of patients receiving EPO. Clinical trials with granulocyte-macrophage (GM-CSF) and granulocyte colony stimulating factor (G-CSF) have reached phase III trials. Both factors show high efficacy to shorten or improve neutropenia related to chemotherapy, bone marrow transplant, or underlying disease. Mechanisms responsible for mucosa protection and improved healing of mucositis observed with both factors remain undetermined yet phase I/II evaluation of IL-3 shows multilineage hemopoietic responses including myeloid, erythroid, and megakaryocyte lineages. Possible anti-cancer effects of hemopoietins achieved by direct action or by increased chemotherapy intensity are currently under investigation.
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PMID:Hemopoietins in clinical oncology. 204 61

The primary objective of this study was to compare the toxicity and hemopoietic effects of s.c. and i.v. recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in patients with primary myelodysplasia. Twenty patients were treated in this phase I crossover-designed study. In three groups of patients, the dose of rhGM-CSF was escalated from 60 to 250 micrograms/m2/day. Each patient was to receive 2 weeks of i.v. (daily 2-h infusion) and s.c. (twice daily) rhGM-CSF separated by a 2-week rest period. The decision to start with i.v. or s.c. administration was by random selection. Toxicity was comparable between i.v. and s.c. administration. At the highest dose level, 63% (five of eight) of the patients developed moderate to severe toxicity. Increases in the absolute neutrophil count showed a dose-response relationship and were more pronounced with s.c. than i.v. administration. Failure to grow in vitro granulocyte-macrophage colonies or a hypocellular marrow (less than or equal to 30%) predicted for a poor response to therapy. No patient had a platelet or a reticulocyte response. No patient progressed to acute leukemia. Compared to a 2-h infusion of i.v. rhGM-CSF, s.c. administration is more myelostimulatory without an increase in toxicity.
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PMID:Comparison of intravenous versus subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor in patients with primary myelodysplasia. 205 92

We studied granulocyte-macrophage (GM) colony formation in chronic myelomonocytic leukemia (CMML, 6 cases), as compared with that in myelodysplastic syndromes (MDS, 6 cases) and myeloproliferative disorders (MPD, 12 cases). GM colony formation of bone marrow cells by colony-stimulating factor (CSF) was normal in CMML and MPD patients, but was decreased in MDS patients. Circulating granulocyte-macrophage progenitors (CFU-GM) were detected in CMML and MPD patients, but not in MDS patients. GM colony formation without CSF was observed in CMML patients, but not in MDS or MPD patients. These endogenous colonies decreased markedly after adherent cell (AdC) depletion, but AdC did not form endogenous colonies in sufficient numbers to explain their marked decrease after AdC depletion. In CMML patients, the numbers of circulating CFU-GM and endogenous colonies correlated with leukocyte and monocyte counts, respectively. The cellular composition of GM colonies was normal in MDS and MPD patients, whereas granulocytic colonies predominated in all CMML patients but one. The CSF-producing capacity of peripheral blood cells was also studied and was found to be increased in CMML patients. This capacity was markedly decreased by AdC depletion; and AdC could produce CSF only in CMML patients. CSF produced by CMML patients supported granulocytic colonies to a greater extent than CSF produced by MDS or MPD patients. These results suggest that enhanced granulopoiesis in CMML patients is closely associated with the possible hyperproduction of granulocytic CSF by their adherent monocytes.
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PMID:Characteristics of granulocyte-macrophage colony formation in chronic myelomonocytic leukemia: a comparative study with other myelodysplastic and myeloproliferative disorders. 211 95

We studied MDS-associated inhibitory activity, which inhibited colony formation in vitro of granulocyte-macrophage progenitors (CFU-GM). Macrophages obtained from MDS bone marrow mononuclear cells (BM-MNC) when pretreated with granulocyte-macrophage colony stimulating factor (GM-CSF) suppressed the growth of normal CFU-GM. These macrophages were designated as 'MDS-derived inhibitory macrophages'. Media conditioned by MDS-derived inhibitory macrophages (MDS-CM) also suppressed the growth of normal CFU-GM. In the MDS-CM, high levels of prostaglandin E2 (PGE2) and ferritin were found. However, MDS-CM did not contain detectable levels of tumour necrosis factor (TNF) or gamma-interferon (gamma-IFN). Antiserum against human placental ferritin and/or against PGE2 blocked the haemopoietic inhibitory activity to some extent. These results suggest that inhibitory macrophages may be responsible for the suppression of granulopoiesis in patients with MDS and that the suppression may be mediated by soluble factors including PGE2 and ferritin.
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PMID:Myelodysplastic syndrome (MDS)-associated inhibitory activity on haemopoietic progenitor cells. 218 Apr 70

An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a compact, three-dimensional spheroid complex from central adipocytes, fibroblastoid cells, and resident macrophages that compartmentalize myeloid, erythroid, and megakaryocyte progenitor cells and their progenies. The Hematon fraction is more than twofold more abundant in progenitor cells when compared to the mononuclear cell (MNC) fraction as gauged by cytological techniques and by analysis of granulocyte-macrophage colony-forming unit (GM-CFU) populations. Individual Hematons may produce, within 2-3 weeks, up to 50,000 hemopoietic cells of different cell lineages in organotypic microcultures. Recombinant human hematopoietic growth factors interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF) significantly stimulated the endogenous cell production of some but not all of the individually treated Hematons, indicating the heterogeneity of factor-responsive cells within the Hematon population. Comparative observations of 184 BM aspirates support the hypothesis that the presence of Hematons in a BM aspirate correlates positively with homeostatic blood cell production, because the Hematon was present in normal BM (31/40) and it was rare among patients with myelodysplastic syndromes (15/53), acute myeloblastic leukemia (7/39), and chronic myelocytic leukemia (5/52). We suggest that the Hematon represents a unifying model around which the variability of fundamental BM functions and dysfunctions can be explored.
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PMID:Hematon, a multicellular functional unit in normal human bone marrow: structural organization, hemopoietic activity, and its relationship to myelodysplasia and myeloid leukemias. 218 30

Prognostic factors affecting the leukemic transformation were studied in 43 patients with myelodysplastic syndrome (MDS). Acute leukemia developed in 17 cases and it was nonlymphocytic leukemia in every case. No remission was achieved following antileukemic therapy and most of the cases proved to be true drug-resistant leukemia. Initial granulopenia, thrombopenia or anemia alone did not influence the occurrence of leukemic transformation but pancytopenia indicates bad prognosis. According to FAB classification especially refractory anemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T) were often followed by leukemic transformation. The granulocyte-macrophage progenitor cell (GM-CFC) content of bone marrow were also studied. The GM-CFC content was decreased in each patient. There was no correlation between GM-CFC number and leukemic transformation, the growth-pattern in agar-gel culture, however, turned out to have prognostic importance. Leukemic type of growth, namely always preceded leukemic transformation.
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PMID:[Factors influencing leukemic transformation in myelodysplastic syndrome]. 219 92

Hexamethylene bisacetamide (HMBA; NSC 95580) is a potent polar-planar differentiating agent of leukemia and solid tumor cell lines in vitro at clinically achievable concentrations. HMBA is currently being studied in patients with myelodysplastic syndrome. Previous phase I trials have demonstrated that HMBA produces hematologic toxicity in morphologically normal bone marrows of patients with solid tumors. Because of concern that HMBA may produce more severe myelotoxicity in patients with myelodysplastic syndrome since these patients have limited hematopoietic reserves, we studied the effects of HMBA on myelodysplastic and normal hematopoietic progenitors in vitro. HMBA concentrations that are optimal for differentiation in vitro (2 to 5 mmol/L) and HMBA concentrations that are being achieved in clinical trials (1 to 2 mmol/L) inhibited the growth of granulocyte-macrophage colony-forming units and erythroid burst-forming units from all 15 patients with myelodysplastic syndrome and all 4 normal subjects, HMBA did not induce proliferation of myelodysplastic or normal progenitors at any concentration; rather, it produced nearly identical inhibition of normal and myelodysplastic hematopoietic progenitors. HMBA also produced quantitatively similar inhibition of clonogenic leukemic growth of two myeloid leukemia cell lines. For a differentiating agent to be effective, it will likely have to either produce both differentiation and proliferation of abnormal hematopoietic progenitors or show selective inhibitory effects on abnormal as compared with normal progenitors. Although the mechanisms responsible for the antiproliferative effects of HMBA cannot be determined from this study, similar inhibitory effects of HMBA on normal and abnormal hematopoietic progenitors suggest that HMBA may be of limited utility in producing and sustaining elevations of peripheral blood cell counts in patients with myelodysplastic syndrome.
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PMID:Effects of the differentiating agent hexamethylene bisacetamide on normal and myelodysplastic hematopoietic progenitors. 225 Mar 14

Thirty-eight consecutive patients with a FAB-classified primary myelodysplastic syndrome (MDS) were investigated for in vitro growth of colony-forming units for granulocyte-macrophage precursors (CFU-GM) and cytogenetic analysis of bone marrow cells. Abnormal CFU-GM growth was found in 30 patients (79%), and clonal chromosome abnormalities were found in 13 patients (34%). The eight patients who showed normal CFU-GM growth were either cytogenetically normal (n = 5), or had a 5q-deletion (n = 3) as single or dominating karyotypic abnormality. Among the 30 patients with reduced or no colony growth, ten patients had a clonal chromosome abnormality. Leukemia developed in eight patients. None of them grew any CFU-GM colonies, and three of them were cytogenetically abnormal at the time of diagnosis of MDS. Analysis of the bone marrow in vitro growth for CFU-GM and the karyotype in patients with MDS emphasizes the close relationship between these disorders and manifest acute leukemia. Subgroups of MDS may be defined by a cytogenetic classification (e.g., the 5q-syndrome), and the CFU-GM growth pattern can be of value for predicting leukemic transformation.
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PMID:Bone marrow in vitro growth and cytogenetic studies in patients with FAB-classified primary myelodysplastic syndromes. 236 12

The aim of the present study was to evaluate the incidence of bone marrow-derived multipotent (CFU-GEMM), megakaryocytic (CFU-Mk), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in 22 patients with myelodysplastic syndromes (MDS), and to investigate the role of hematopoietic accessory cells (T-lymphocytes and monocytes) as a possible cause of growth derangement. As compared to normal controls (n = 15), growth values in the 22 patients (mean +/- SEM) were significantly reduced for CFU-GEMM (0.4 +/- 0.1 versus 7 +/- 1, P less than 0.0005), CFU-Mk (1.4 +/- 0.5 versus 18 +/- 4, P less than 0.0005), BFU-E (2.2 +/- versus 40 +/- 6, P less than 0.0005), and CFU-GM (19 +/- 5 versus 65 +/- 10, P less than 0.0005). The growth of CFU-GEMM was abnormal at an early stage in the clinical development of MDS, sometimes even when CFU-GM formation was still normal. Colony-formation was unaffected by removal of hematopoietic accessory cells. Although no correlation was found between the incidence of lineage-restricted progenitors and the degree of peripheral cytopenia, derangement of colony growth was more pronounced in patients with worse prognosis. We conclude that: (i) the grossly defective CFU-GEMM growth supports the concept of MDS as clonal disorders of hematopoietic multipotent stem cells; (ii) a progressive impairment of in vitro hematopoiesis occurs in association with the clinical progression of the myelodysplastic syndromes.
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PMID:In vitro growth of bone marrow-derived multipotent and lineage-restricted hematopoietic progenitor cells in myelodysplastic syndromes. 250 Nov 71


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