The effects of 5-aza-2'-deoxycytidine (Decitabine) on the platelet count in patients with intermediate and high-risk myelodysplastic syndromes.

5-Aza-2'-deoxycytidine, a DNA-hypomethylating agent, can induce clinical remissions in patients with high-risk myelodysplastic syndromes (MDS). During treatment an increase in platelet count is frequently the first positive event to be seen. In this study, we analyzed the platelet response of patients with high-risk MDS on low-dose 5-aza-2'-deoxycytidine therapy. We evaluated 162 from the 170 patients entered in three consecutive Phase II studies. One hundred twenty-six of them were thrombocytopenic at start of the therapy. All patients had an IPSS risk score of Intermediate I or higher. A rise in platelet count preceded a good trilineage response. In 58% of the thrombocytopenic patients a platelet response was already seen after one cycle of therapy. During therapy 69% of the patients with a low platelet count showed a response. Due to disease progression the final response rate was 63% in thrombocytopenic patients. No correlation was found between the platelet response and either the presence or absence of an adequate number of megakaryocytes or serum thrombopoietin levels. However, platelet response strongly predicted for overall survival (P < 0.0001). 5-Aza-2'-deoxycytidine has a clinically significant, often long lasting, effect on the platelet count in a substantial number of high-risk MDS patients.