Danazol treatment of myelodysplastic syndromes

Authors

  • Edward A. Stadtmauer,

    Corresponding author
    1. Section of Hematology/Oncology, Department of Medicine, Cancer Center, and Department of Pathology and Laboratory Medicine of the University of Pennsylvania School of Medicine
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  • Peter A. Cassileth,

    1. Section of Hematology/Oncology, Department of Medicine, Cancer Center, and Department of Pathology and Laboratory Medicine of the University of Pennsylvania School of Medicine
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  • Marian Edelstein,

    1. Section of Hematology/Oncology, Department of Medicine, Cancer Center, and Department of Pathology and Laboratory Medicine of the University of Pennsylvania School of Medicine
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  • Janet Abrahm,

    1. Section of Hematology/Oncology, Department of Medicine, Cancer Center, and Department of Pathology and Laboratory Medicine of the University of Pennsylvania School of Medicine
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  • Alan D. Schreiber,

    1. Section of Hematology/Oncology, Department of Medicine, Cancer Center, and Department of Pathology and Laboratory Medicine of the University of Pennsylvania School of Medicine
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  • Peter C. Nowell,

    1. Section of Hematology/Oncology, Department of Medicine, Cancer Center, and Department of Pathology and Laboratory Medicine of the University of Pennsylvania School of Medicine
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  • Douglas B. Cines

    1. Section of Hematology/Oncology, Department of Medicine, Cancer Center, and Department of Pathology and Laboratory Medicine of the University of Pennsylvania School of Medicine
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Dr Edward Stadtmauer, University of Pennsylvania Cancer Center, 6 Penn Tower, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, U.S.A.

Abstract

Summary. 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 Fcγ receptors. Treatment with danazol was associated with a decline in monocyte Fcγ 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 Fcγ receptors. Danazol treatment was associated with minimal toxicity, but clinically meaningful responses were rare.

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