Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N4-Palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was administered PO to 76 patients with acute leukemia, myelodysplastic syndromes (MDSs), and myeloproliferative disorders (MPDs). Of 20 patients with acute myelogenous leukemia, 2 achieved complete remission, and the only patient with acute lymphoblastic leukemia achieved partial remission. Remission was reached with PLAC 100-300 mg/day 25-66 days after the start of therapy. Among 22 patients with MDS, 1 patient achieved a good response and 8 achieved partial response. Responses were reached with PLAC 50-200 mg/day 7-153 days (median, 33 days) after the start of therapy. Improvement of polycythemia was observed in all 5 patients with polycythemia vera, and reduction of thrombocytosis was observed in 5 out of 6 patients with essential thrombocythemia and myelofibrosis. An antileukemia effect was noted in 1 of 5 with chronic myelogenous leukemia. Major side effects were gastrointestinal toxicities and myelosuppression. In spite of the disadvantages, such as unpredictable absorption and a lower response rate to acute leukemia compared with its parent compound, this antileukemia Ara-C analogue that is administrable PO will be useful in the treatment of MDSs and MPDs, which do not necessarily require admission to hospital, and in the treatment of acute leukemia of the aged, a condition for which intensive chemotherapy is not appropriate.
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PMID:Treatment of leukemia and myelodysplastic syndromes with orally administered N4-palmitoyl-1-beta-D-arabinofuranosylcytosine. 371 96

Neutrophil alkaline phosphatase activity was estimated in 194 patients; 59 cases of chronic myeloid leukaemia (CML), 42 cases of polycythaemia vera (PV), 24 cases of primary myelofibrosis, 7 cases of idiopathic thrombocythaemia, 6 cases of leukaemoid reaction, 19 cases of secondary polycythaemia (PS) and 37 cases of the primary myelodysplastic syndrome (MDS). According to NAP activities the groups proved to be separate entities (p less than 0.00025). The incidence of decreased NAP score in the CML group was 85% and differed significantly from the other groups as a whole, as well as separately (p less than 0.001). The MDS group, the only group besides CML that showed decreased scores, also differed significantly from the others (p less than 0.001). The PS group, nearly always showing normal scores, differed significantly from the PV group (p less than 0.0052). A method evaluating single cell NAP activity proved superior to the score method in discriminating between the different groups. Thus, the incidence of decreased activity in the CML group was 93% compared with 85% by the score method and the incidences of increased activity in the PV, MP, IT, and LR groups were 79% to 100% compared with 25% to 67% by the score method. The latter difference was statistically significant (p = 0.029).
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PMID:Evaluation of neutrophil alkaline phosphatase (NAP) activity in untreated myeloproliferative syndromes and in leukaemoid reactions. 404 68

Platelet function was studied in 17 patients with preleukaemia and the results were compared with those of 28 patients with other chronic myeloproliferative disorders. The test pattern included bleeding time (Ivy), platelet retention (Hellem II), PF-3 activity and availability after exposure to ADP and kaolin, and ADP-, epinephrine-, collagen- and ristocetin-induced aggregations. Platelet function was frequently impaired in patients with preleukemia. The defects were similar to those found in other myeloproliferative disorders. The most consistent finding was defective aggregation. Patients with thrombocytosis and/or with increased amounts of megakaryocytes in the bone marrow had fewer defects in platelet function. Retention defect was more common in patients with hypolobulated megakaryocytes, especially in those having a specific marker, the 5q- chromosome, in their bone marrow cells.
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PMID:Platelet function in preleukaemia. 746 20

Since all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF) not only enhance proliferation and differentiation of normal myeloid cells but also synergistically promote the differentiation of myeloid leukemic blast cells in vitro, we have started a pilot study of combined treatment with ATRA and G-CSF in patients with myelodysplastic syndrome, to analyze the effect of these drugs on hematopoietic differentiation. ATRA was given at 45 mg/m2/day p.o. from week 1-12 and G-CSF at 5 micrograms/kg/day s.c. from week 5-12 with dose modifications according to the absolute neutrophil counts (ANC). A total of 15 patients, predominantly with refractory anemia, were treated. During initial ATRA therapy, a bilineage response with increases of both ANC and platelet counts occurred in three patients. During combined ATRA/G-CSF therapy, ANC increased in all patients, and platelets increased in three out of 14 evaluable patients. An increase in hemoglobin concentration and a decrease in transfusion requirements occurred in one patient each. In the bone marrow, the myeloid-to-erythroid ratio increased during ATRA treatment and remained increased during concomitant G-CSF administration, while the maturation index of myeloid cells increased only in response to ATRA therapy, but returned to baseline during ATRA/G-CSF treatment. Cytogenetic analysis demonstrated persistence of the abnormal clones in all patients. The number of circulating progenitor cells CFU-GM increased in all patients studied. Serum concentrations of the soluble TNF receptor and IL-2 receptor both increased, while TNF-alpha--already elevated prior to therapy--and soluble ICAM-1 concentrations did not significantly change. Adverse effects included dermatitis and cheilosis in most patients, and a drop in platelet counts related to G-CSF in one patient. The pilot study demonstrates that the combination treatment with ATRA/G-CSF is well tolerated, leading to normalization of ANC in most, and improvement of platelets and red blood cells in a subgroup of patients.
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PMID:Effect of combination therapy with all-trans-retinoic acid and recombinant human granulocyte colony-stimulating factor in patients with myelodysplastic syndromes. 751 Mar 54

A 64-year-old woman with multiple myeloma, IgG lambda type Durie-Salmon Stage II, was admitted because of gradually developing anemia and increased blasts with abnormal karyotype in her bone marrow after 10 years of treatment. The chromosomal analysis showed 44, XX, del(5q), del(7q), -9, add(12p), -21, typical of secondary MDS due to the cumulative alkylating agents. Thrombocytosis concomitantly occurred with emergence of chromosomal abnormality, but the serum interleukin 6 level was not elevated, which suggested that it was related to development of secondary MDS.
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PMID:[Multiple myeloma developing myelodysplastic syndrome with thrombocytosis]. 756 1

CGL is a highly specific disease that is defined by strict hematologic parameters that include a pathognomonic differential leukocyte count. Usually CGL is accompanied by the presence, in bone marrow cells, of the Ph chromosome, the first chromosomal anomaly to be regularly associated with a human neoplastic disease. CGL is predominantly a disease of the productive middle years of life, which maximizes its adverse impact on family life and family economics. The disease is of worldwide distribution and there is a slight male preponderance. The disease is characterized by an initial chronic phase when it behaves as a differentiated neoplasm and responds very well to simple, nonintensive therapy. After a variable interval, CGL undergoes metamorphosis to a refractory phase that responds poorly or sometimes not at all to therapy, even when this is intensive. At the stage of metamorphosis a great variety of clinical and hematologic pictures occur, and CGL may mimic a myeloproliferative disease, a myelodysplasia, a subacute leukemia, AML, or ALL. The old concept of an abrupt, explosive transition from the chronic phase to a so-called blastic crisis is incorrect: this rarely occurs and in most patients who are carefully followed, CGL is observed to undergo two or more stepwise evolutions, eg, from chronic phase to an accelerated myeloproliferative phase to a phase that resembles AML. Many patients with CGL conform to an established pattern of clinical features. There is a history of insidious symptoms of anemia and of splenomegaly. The physical signs are those of pallor and marked splenomegaly, while the hematologic findings are of moderate anemia, moderate thrombocytosis, and a marked granulocytic leukocytosis with a specific differential count. The radiologic findings are typically normal. Diagnostic difficulty seldom arises with this classic presentation. The patient who is detected at an early stage of CGL may lack the history, physical signs, and fully developed hematologic picture of CGL. Before the availability of cytogenetic studies, the diagnosis could only be established with confidence by observing the patient until the typical features of the disease emerged. Also considered are the less frequent but important atypical presentations of CGL. The symptoms and complaints, findings on examination, complications and hematologic findings may depart from the typical case in a bewildering variety of ways, so that the diagnosis may be difficult, indeed, CGL is generally not the initial diagnosis that is made. When the patient with CGL has received treatment, it is usual for he or she to become asymptomatic, with no abnormal physical signs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical manifestations of chronic granulocytic leukemia. 763 35

We describe a case characterized by the onset of bone marrow hypoplasia. After treatment with steroid and anabolic compounds, it evolved into a myelodysplastic syndrome (MDS) as demonstrated by morphological and karyotypic analysis. Despite the dysplastic nature of the disorder, a unique feature was its association with a high platelet count. The pathogenesis of the thrombocytosis could not be clearly identified. In fact, the course of the disease was complicated by severe infections that, together with therapy, could have played some role in stimulating thrombopoiesis. However, since MDS can precede or follow a chronic myeloproliferative disease, it is also possible that the platelet elevation in our patient could have been sustained by a primitive thrombocyte disorder.
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PMID:Myelodysplastic syndrome and thrombocytosis: a random association? 789 11

A case of pyoderma gangrenosum of the lip occurring in association with paroxysmal nocturnal haemoglobinuria is described. This is an extremely rare association, which has been documented in the literature on only two previous occasions. Pyoderma gangrenosum (PG) is an uncommon ulcerative skin disorder of unknown aetiology. Its clinical appearance is often distinctive, with established lesions consisting of a necrotic ulcer surrounded by a ragged undermined violaceous edge. Lesions are usually painful and are most often found on the lower limbs but can occur on the trunk, head and neck. The diagnosis is essentially clinical as there are no characteristic histopathological changes. Since its original description in 1930, PG has been frequently associated with a number of underlying systemic diseases. Foremost among these are inflammatory bowel disease and inflammatory polyarthritis. The association with haematological disorders is also well recognized, and includes acute and chronic lymphocytic and myeloid leukaemias, polycythaemia rubra vera, myelofibrosis, myelodysplastic syndrome, essential thrombocythaemia, hypogammaglobinaemia, monoclonal gammopathy, multiple myeloma and non-Hodgkin's lymphoma. We report a case of PG occurring on the lower lip of a 26-year-old man recently diagnosed as having paroxysmal nocturnal haemoglobinuria (PNH).
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PMID:Pyoderma gangrenosum associated with paroxysmal nocturnal haemoglobinuria. 803 97

Five patients with the classical clinical syndrome associated with a deletion of the long arm of chromosome 5, i.e., anemia, macrocytosis, and thrombocytosis, or a normal platelet count, were treated successfully with subcutaneous low-dose cytosine arabinoside (LDARA-C). Prior therapy with other drugs had failed in four of the five patients. A total of nine complete and one partial hematologic responses were induced in five patients. Duration of the first hematologic response ranged from 3 to 30+ months. Two patients (cases 3 and 4) continue in their first hematologic response at 29 and 30 months. Upon relapse, up to three responses could be reinduced in two patients. Duration of the subsequent hematologic responses in case 1 was 16, 8, and 10 months and case 2 achieved two responses of 15 and 18+ months duration. LDARA-C therapy was associated with mild to severe neutropenia and moderate to severe thrombocytopenia. Thus, subcutaneous LDARA-C is highly effective in the treatment of patients with myelodysplasia associated with deletion of the long-arm of chromosome 5 (5q-).
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PMID:Low-dose ARA-C consistently induces hematologic responses in the clinical 5q- syndrome. 803 87

Fifty consecutive patients, 30 of whom had polycythaemia vera (PV), 10 essential thrombocythaemia (ET), and 10 myelofibrosis (MF), entered a long-term prospective study of hydroxyurea (HU) therapy. The indication for treatment was mainly thrombocytosis or symptomatic splenomegaly. Control of erythrocytosis and thrombocytosis was achieved in 70% of the patients. Continuous maintenance treatment was required. In 15% of responding patients with thrombocytosis, unexpected rises of the platelet count occurred during maintenance therapy. Severe thrombo-embolic events occurred in 6 patients. The size of the spleen decreased in all patients who did not develop thrombocytopenia and could absorb adequate HU doses. Acute leukaemia (AL) was diagnosed in 9 patients and a myelodysplastic syndrome in one. Seven of them had been treated with HU alone. Among the patients with PV and ET, 6 developed AL and 4 of them were treated with HU alone (3 PV and 1 ET), giving an incidence of 10.5%. In previously untreated patients with initially normal karyotypes (n = 19), chromosome abnormalities developed during HU therapy in 7 (37%). Our results indicate that HU should be regarded as leukaemogenic, at least when used for treatment of PV and allied diseases. Since myelosuppressive treatment of PV does not prolong survival, the use of HU should be restricted to patients in whom the treatment indication outweights the risk of leukaemia induction.
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PMID:Acute leukaemia after hydroxyurea therapy in polycythaemia vera and allied disorders: prospective study of efficacy and leukaemogenicity with therapeutic implications. 816 92


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