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.