UMLS:C0026986 - FACTA Search

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

Three new cases of monosomy 7 are described. Two children, before onset of overt leukemia, had a preleukemic state: one with thrombopathy and myelodysplastic syndrome, the other with a moderate splenomegaly and an absolute monocytosis. In these two cases the leukemia was chemoresistant. The last child had a subacute myelomonocytic syndrome (juvenile type of chronic myelogenous leukemia) without high fetal hemoglobin value. She died from cachexia. The poor prognosis of monosomy 7 is underlined and such a chromosome deletion should be searched in myeloproliferative syndrome with monocytosis.
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PMID:[Bone marrow monosomy 7 in children]. 324 43

Of 511 cases of brucellosis studied between December 1983 and February 1986, four (0.8%) had sternoclavicular (STCL) arthritis. Two were male and two female, and only one was younger than 50 years old. All four cases had significantly high specific IgG antibody titres (1 of 1280), measured by the indirect immunofluorescent (IIF) test, and two had Brucella melitensis isolated from their blood. In two cases, STCL arthritis was the presenting problem, and it was associated in one with ankle arthritis, hepatitis, renal impairment, orogenital ulcers and a haematological picture of myelodysplasia; in the other it was a relapsing STCL arthritis. In the remaining two cases, STCL arthritis was part of an extensive osteoarticular disease, which was associated in one with cachexia, liver cirrhosis, heart failure and prostatitis with urine retention, and in the other with severe thrombocytopenia. Excellent results were obtained from six to eight weeks' therapy with streptomycin, rifampicin and cotrimoxazole or tetracycline.
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PMID:Brucellar sternoclavicular arthritis, the forgotten complication. 325 Mar 41

This study was aimed to examine whether a combination of all-trans retinoic acid (ATRA), 1, 25-dihydroxyvitamin D(3) and androgen possesses the therapeutic value for the MDS-refractory anemia (MDS-RA), and to analyze the mechanisms in detail. 62 cases receiving a scheme of combination of ATRA, 1, 25-dihydroxyvitamin D(3) and androgen (group A) were monitored. The remaining 33 cases (group B) were provided with vitamin supplementation, chalybeate drugs, and one or two of the combination. Bone marrow aspiration and biopsy were performed for collecting the specimens at the baseline and afterwards. The conditions of the patients were monitored by means of weekly complete blood counts and the monthly examination, including toxicity test, physical examination, electrocardiography, and biochemistry panel. The results showed that after treating for 8 weeks in group A, 4 out of 62 patients showed complete remission and 12 patients showed partial remission according to the defined response criteria, and 43 patients (69.35%) showed hematological improvement (HI). The further treatment for 16 out of 62 patients (25.81%), 13 failures (10 deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(5)) with a median survival interval of 26.25 months, were observed and interrupted for some reasons. However, partial remission was observed only in 3 patients in group B, and HI amounted to 51.51%. Furthermore, the disease progression was observed in 12 out of 33 patients (36.36%) with a median survival interval of 16 months, 9 failures (including 6 deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(4)). The overall ratios of survival for 3 and 5 years in group A, which received the combination, reached to 69.24% and 53.72% respectively, in comparison with 52.23% and 31.34% in the patients of group B (log-rank, P = 0.016). The following requirements, if were met, would be significant for prognosis: the combination regiment, no transformation, children, no complication, female, 90-120 g/L of hemoglobin concentration, normal cellular bone marrow and uni-cytopenias (P < 0.05). Moreover, Cox regression showed that therapy, transformation and age are all the independent factors (P < 0.05). It is concluded that the combination of above mentioned 3 drugs may be effective and safe treatment for the patients with MDS-RA. Its relevant mechanisms can be involved in the combination, that elicits a wide range of pharmacological effects, such as differentiation, anti-tumor-promotion, anti-apoptosis, anti-angiogenesis, anti-cachexia and immunoregulation.
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PMID:[Retrospective observation of curative effects on MDS refractory anemia with combination of all-trans retinoic acid, 1, 25-dihydroxyvitamin D3 and androgen]. 1627 59

Leukemic patients of different classifications are associated with anemia. Such clinical conditions are often referred to as refractory anemia, paraoxymal nocturnal hemoglobinuria, hemolytic uremia and autoimmune hemolytic anemia, all of which could be categorized as the cancer cachexia. In the present work, we have studied the overall morphology of intact red cells in different leukemic patients along with patients of hypoplastic anemia (HPA) by scanning electron microscopy. We have also studied the ultrastructure of the red cell surface membranes by transmission electron microscopy. For all experiments, erythrocytes from normal individuals served as controls. We have shown direct evidence of the altered red cell (RBC) membrane morphology irrespective of the hemoglobin status of the patients which includes (1) presence of large central holes in RBCs of acute myeloid leukemia (AML), (2) presence of thorn- and horn-like structure in RBCs of acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) and (3) flaccid appearance of RBCs in chronic lymphocytic leukemia (CLL) patients. A mixture of the above mentioned structures were found in the red cells of patients suffering from myelodysplastic syndrome (MDS) and in case of patients of HPA the RBCs lost the normal biconcave structures. TEM studies revealed presence of pores with diameters ranging from 100 to 200nm on the RBC membrane surface of myeloid leukemia with AML being the most prominent among others. Such pathophysiological alterations of the RBC morphology in leukemic patients could be identified as characteristic signature of the onset of anemia associated with the disease.
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PMID:Red cell morphology in leukemia, hypoplastic anemia and myelodysplastic syndrome. 1687 91

Thalidomide is an anti-angiogenic agent currently used to treat patients with malignant cachexia or multiple myeloma. Lenalidomide (CC-5013) is an immunomodulatory thalidomide analogue licensed in the United States of America (USA) for the treatment of a subtype of myelodysplastic syndrome. This two-centre, open-label phase I study evaluated dose-limiting toxicities in 55 patients with malignant solid tumours refractory to standard chemotherapies. Lenalidomide capsules were consumed once daily for 12 weeks according to one of the following three schedules: (I) 25 mg daily for the first 7 d, the daily dose increased by 25 mg each week up to a maximum daily dose of 150 mg; (II) 25mg daily for 21 d followed by a 7-d rest period, the 4-week cycle repeated for 3 cycles; (III) 10 mg daily continuously. Twenty-six patients completed the study period. Two patients experienced a grade 3 hypersensitivity rash. Four patients in cohort I and 4 patients in cohort II suffered grade 3 or 4 neutropaenia. In 2 patients with predisposing medical factors, grade 3 cardiac dysrhythmia was recorded. Grade 1 neurotoxicity was detected in 6 patients. One complete and two partial radiological responses were measured by computed tomography scanning; 8 patients had stable disease after 12 weeks of treatment. Fifteen patients remained on treatment as named patients; 1 with metastatic melanoma remains in clinical remission 3.5 years from trial entry. This study indicates the tolerability and potential clinical efficacy of lenalidomide in patients with advanced solid tumours who have previously received multi-modality treatment. Depending on the extent of myelosuppressive pre-treatment, dose schedules (II) or (III) are advocated for large-scale trials of long-term administration.
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PMID:Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide: phase I clinical trial of three dosing schedules in patients with solid malignancies. 1689 62

Gelatinous bone marrow transformation (GBMT) is a rare pathologic entity of unclear etiology characterized by adipose cell atrophy, focal hematopoietic tissue hypoplasia, and a distinct eosinophilic substance that stains with Alcian blue at pH 2.5. It is traditionally described in the context of malnutrition and cachexia from generalized disease and is important to identify because of its potential reversibility. Several recent case reports have described GBMT in patients with chronic myeloid leukemia (CML) on the first-generation tyrosine-kinase inhibitor (TKI) imatinib. Here, we describe a case of gelatinous transformation in a patient with CML receiving the second-generation TKI dasatinib who subsequently developed clonal cytogenetic abnormalities in Philadelphia chromosome negative cells with excess peripheral blasts consistent with advanced secondary myelodysplastic syndrome. While the development of clonal cytogenetic abnormalities in Philadelphia-negative cells has been frequently described in the setting of TKI, most abnormalities are transient and generally do not effect disease progression and/or transformation like in this case. Remarkably, after TKI discontinuation, repeat bone marrow biopsies had markedly diminished amounts of gelatinous transformation - supporting reversible GBMT with TKI removal. We review the relevant pathophysiology underlying our patient's possible therapeutic-mediated complications during CML therapy in an attempt to better understand the role of TKIs in the pathogenesis of these conditions.
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PMID:Gelatinous bone marrow transformation and emergence of clonal Philadelphia-negative cytogenetic abnormalities with excess blasts in a patient with chronic myeloid leukemia treated with dasatinib. 3087 49

Chronic myelomonocytic leukemia (CMML) constitutes a hematopoietic stem cell (HSC) disorder characterized by prominent monocytosis and myelodysplasia. Although genome sequencing has revealed the CMML mutation profile, the mechanism of disease development remains unclear. Here we show that aberrant histone acetylation by nucleoporin-98 (NUP98)-HBO1, a newly identified fusion in a patient with CMML, is sufficient to generate clinically relevant CMML pathogenesis. Overexpression of NUP98-HBO1 in murine HSC/progenitors (HSC/Ps) induced diverse CMML phenotypes, such as severe leukocytosis, increased CD115⁺ Ly6C^high monocytes (an equivalent subpopulation to human classical CD14⁺ CD16^- monocytes), macrocytic anemia, thrombocytopenia, megakaryocyte-lineage dysplasia, splenomegaly, and cachexia. A NUP98-HBO1-mediated transcriptional signature in human CD34⁺ cells was specifically activated in HSC/Ps from a CMML patient cohort. Besides critical determinants of monocytic cell fate choice in HSC/Ps, an oncogenic HOXA9 signature was significantly activated by NUP98-HBO1 fusion through aberrant histone acetylation. Increased HOXA9 gene expression level with disease progression was confirmed in our CMML cohort. Genetic disruption of NUP98-HBO1 histone acetyltransferase activity abrogated its leukemogenic potential and disease development in human cells and a mouse model. Furthermore, treatment of azacytidine was effective in our CMML mice. The recapitulation of CMML clinical phenotypes and gene expression profile by the HBO1 fusion suggests our new model as a useful platform for elucidating the central downstream mediators underlying diverse CMML-related mutations and testing multiple compounds, providing novel therapeutic potential.
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PMID:NUP98-HBO1-fusion generates phenotypically and genetically relevant chronic myelomonocytic leukemia pathogenesis. 3094 97