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)

Peripheral cytopenias are common in patients with myelodysplastic syndromes. We previously successfully treated three such patients with improvement of some cytopenias with the impeded androgen danazol. To confirm this finding and elucidate the mechanism of response, we treated an additional 22 patients with myelodysplasia with oral danazol (600-800 mg daily) for 3-12 months. Eleven of 22 evaluable patients taking danazol met our criteria for improvement of peripheral counts, mainly thrombocytopenia. Chromosome analysis, marrow culture studies and serial bone marrow biopsies revealed no alteration of the abnormal clone or normal haematopoiesis in patients on danazol therapy. This suggested that improvement in blood counts was not related to modulation of ineffective haematopoiesis. Investigation of the thrombocytopenia in these patients revealed that most patients presented with markedly elevated platelet associated IgG (PAIgG), elevated plasma platelet-bindable IgG (PBIgG), and an elevated number of monocyte Fc gamma receptors. Treatment with danazol was associated with a decline in monocyte Fc gamma receptor number without significantly altering the elevated PAIgG or PBIgG levels. These results are similar to our observations in patients treated with danazol for chronic idiopathic thrombocytopenia purpura (ITP). Our data suggest that a component of the thrombocytopenia occurring in patients with myelodysplasia may be due to enhanced peripheral blood cell destruction by abnormal macrophages. Danazol may modulate cytopenia by decreasing the number of monocyte Fc gamma receptors. Danazol treatment was associated with minimal toxicity, but clinically meaningful responses were rare.
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PMID:Danazol treatment of myelodysplastic syndromes. 825 1

Danazol, an attenuated androgen developed for the treatment of endometriosis, has recently been found useful in the treatment of several hematologic disorders, including idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, and others. Our studies of the past 6 years have demonstrated that danazol is advantageous in the treatment of AIHA, and in specifically defined populations of ITP patients. Of 96 ITP patients treated with danazol 61% overall had excellent/good responses, but this rate varied markedly with prognostic factors, e.g. 82% in older women versus only 18% in younger women. Of 28 AIHA patients, 77% with idiopathic type and 60% with secondary type were excellent/good responders. When the drug was discontinued after 1 year or more of therapy, lasting unmaintained remissions of up to 5 years were often observed in both ITP and AIHA, a notably important benefit. The side-effects of danazol are generally much less serious than with glucocorticoids. Glucocorticoids can be tapered off and in most cases discontinued completely with danazol therapy in AIHA and chronic ITP. Approximately one third of ITP patients who failed on glucocorticoids are successfully maintained on danazol. Its mechanism of action in these disorders is currently under study in our laboratory, stimulated by new findings. Tentatively, danazol appears to modify cell membranes in a manner leading to specific immune modulations, as discussed. Further study is warranted to explore its application to other autoimmune and membrane-related disorders, and to clarify its mechanism of therapy.
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PMID:Efficacy of danazol in hematologic disorders. 212 61

In a dose escalation study we tested the feasibility and tolerance of high-dose recombinant human erythropoietin (r-HuEPO) therapy in four patients with ineffective erythropoiesis due to myelodysplastic syndromes (MDS) or paroxysmal nocturnal hemoglobinuria (PNH). Recombinant human EPO was administered i.v. with an initial dose of 50 U/kg body weight (BW) three times per week. The dose was increased by steps of 25 or 50 U/kg bW with intervals of 1-4 weeks up to a maximum dose of 500 U/kg BW three times per week. All patients were treated as outpatients. Pre-study treatment with cyclosporin A and/or Danazol was continued in three patients. In one patient r-HuEPO was discontinued after 20 weeks because of relapse of severe aplastic anemia. No major side effects were observed even at the maximum dose. One patient with PNH showed an increase of hemoglobin from 89 to 139 g/liter that permitted monthly phlebotomies to reduce his iron overload. In one patient with MDS the reticulocyte count increased from 2.5 to 50 x 10(9)/liter, and the transfusion requirement decreased to 2 U every 3-4 weeks instead of every 2 weeks. Two patients did not complete the whole treatment period and showed no rise in reticulocyte count. We conclude that high dose r-HuEPO therapy is feasible in patients with anemia due to MDS or PNH. High-dose r-HuEPO appears to have some effect on anemia due to ineffective erythropoiesis in a subgroup of patients. Further studies are needed to identify potential responders and to define the optimal administration of r-HuEPO.
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PMID:High-dose recombinant human erythropoietin for treatment of anemia in myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria: a pilot study. 222 80

Sixteen unselected untreated patients with primary myelodysplastic syndromes (MDS) and various combinations of blood cytopenia were treated with danazol, an attenuated androgen reported to be of some value in these conditions. After a 12 week trial (danazol 600 mg/day/p.o.), anaemia improved in 4/14 patients, with transfusional requirements being reduced by 50% or more in four other cases (response 57%). An enhanced reticulocyte production was documented in 6/13 cases (46%), and thrombocytopenia resolved in 5/8 (62%). Results of the granulocyte count were less satisfactory, with only one partial response obtained among five cases. A normalization of the monocyte count was seen in 3/5 patients with chronic myelomonocytic leukaemia, with one of them achieving a complete haematological and clinical remission lasting 6 months. Circulating blast cells decreased significantly (50% or more) in 4/6 cases. Although clinical symptoms from anaemia and bleeding disappeared in responsive cases, four patients developed acute non-lymphocytic leukaemia. Danazol was well tolerated and produced no acute or chronic toxicity. The drug appears useful in the management of anaemic and thrombocytopenic MDS patients.
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PMID:Therapeutic efficacy of danazol in myelodysplastic syndromes. 318 Dec 70

20 patients with myelodysplastic syndromes (MDS) were treated with danazol, 800 mg daily in 4 divided doses. 18 patients were evaluable for response. 3 patients (17%), whose principal problem was anemia, responded to treatment, but only with an increase in platelet count. Responses were short-lived and lacked clinical significance. No patients with anemia or leukopenia responded to treatment and none of the 7 patients with a platelet count less than 30 x 10(9)/l responded. Danazol appears to have limited clinical utility in the treatment of MDS. However, occasional patients with thrombocytopenia may benefit.
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PMID:Danazol in the treatment of myelodysplastic syndromes. 331 76

Platelet-associated IgG was markedly elevated in three patients with myelodysplasia and severe thrombocytopenia that had become refractory to platelet transfusions. The patients were treated with danazol because of its efficacy in treating immune thrombocytopenic purpura where platelet destruction is primarily mediated by IgG autoantibodies. After danazol therapy, the platelet counts of each patient rose and clinical bleeding stopped, and a decline in hemolysis was seen in two patients. Danazol probably impeded the peripheral clearance of cells by macrophages; however, a beneficial effect of danazol on hematopoiesis cannot be excluded.
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PMID:Danazol therapy in myelodysplasia. 400 89

We prospectively treated 46 patients with favorable myelodysplastic syndrome classified as refractory anemia (RA), refractory cytopenia (RC), or refractory anemia with ringed sideroblasts (RARS). These patients received one of two schedules of 13-Cis-Retinoic Acid (low dose 80 mg daily for 6 months vs. high dose 200 mg po daily for 3 months), or Danazol (800 mg po daily for 3 months), and were crossed over to the alternative drug in the absence of response or at progression. Using strict criteria of response we found little objective evidence of activity for either compound. Only two minor responses were seen among 22 patients treated with low dose 13-CRA, 1 response among 20 cases that received high dose 13-CRA, and 1 partial response and 1 minor response to Danazol among 34 cases. Neither 13-Cis-Retinoic Acid nor Danazol appear active enough in patients with favorable myelodysplastic syndrome to justify their use.
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PMID:Myelodysplastic syndrome treatment with danazol and cis-retinoic acid. 771 70

Danazol has been used with success in some hematological diseases, but there is no report of this treatment in acute leukemia. We report here a case of remission of myelodysplastic syndrome with myelofibrosis in transformation after danazol therapy in a 72-yr-old man. The role of danazol in remission induction is briefly discussed.
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PMID:Remission of transformed myelodysplastic syndrome with fibrosis after danazol therapy. 1207 39

Thrombocytopenia is a poor prognostic indicator in the myelodysplastic syndromes (MDS). Treatment options for patients with symptomatic thrombocytopenia are limited. Danazol, an attenuated androgen, may have some efficacy in increasing the platelet count of patients with MDS. We retrospectively reviewed 33 patients with primary MDS who were treated with danazol for 6 or more weeks. After 6 weeks on danazol, the mean platelet count increased from 42 x 10(9)/L to 60 x 10(9)/L (P < 0.015), and 25 out of 33 patients (76%) had an increase in their platelet counts. Following 12 weeks of treatment, the mean platelet count increased to 67 x 10(9)/L (P < 0.005), and 21 out of 29 patients (72%) had an increase in their platelet counts. Seven out of nine patients no longer required platelet transfusions because bleeding stopped after 6 weeks on danazol. Mean duration of response was 10 months (range 2-68 months). Responses were seen in all French-American-British (FAB) subtypes and in all International Prognostic Scoring System (IPSS) scores. Therapy was well tolerated. Danazol may be effective in MDS patients who are thrombocytopenic.
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PMID:Danazol for the treatment of thrombocytopenia in patients with myelodysplastic syndrome. 1241 May 70

With prolonged life expectancy, immune thrombocytopenia (ITP) is frequent in elderly people. In this setting, ITP diagnosis is challenging because of the concern about an underlying myelodysplastic syndrome. Studies of older adults are lacking, and recommendations for treatment are based mainly on expert opinion. The therapeutic strategy differs from that for younger patients and must take into account the greater risk of bleeding and thrombosis, presence of comorbidities, possible impaired cognitive performance or poor life expectancy and concomitant medications, such as anticoagulant and antiplatelet therapy. Steroids and intravenous immunoglobulin (IVIg) therapy remain the first-line treatments in elderly patients, but prolonged treatment with steroids should be avoided and IVIg treatment may lead to renal failure. Splenectomy is less effective than in young patients and risk of thrombosis is increased. Severe co-morbidities can also contraindicate surgery. Therefore, other second-line treatments are frequently preferred. Danazol and dapsone can be an option for the less severe ITP form. Rituximab is a good option except in patients with a history of infection or with hypogammaglobulinaemia. Thrombopoietin agonists are attractive, especially for patients with severe comorbidities or with limited life expectancy but the risk of thrombosis is a concern.
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PMID:How we manage immune thrombocytopenia in the elderly. 2706 54


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