title: Anagrelide is effective in treating patients with hydroxyurea-resistant thrombocytosis in patients with chronic myeloid leukemia.
abstract: We report phase II trial results of the use of oral anagrelide hydrochloride for treating 38 patients with hydroxyurea (HU)-resistant thrombocytosis accompanying chronic myeloid leukemia (CML). Anagrelide's efficacy was well established during a phase II study of more than 400 patients with one of the four myeloproliferative disorders: essential thrombocythemia, polycythemia, idiopathic myelofibrosis, and CML. In the last subgroup, there were 114 CML patients with significant thrombocytosis treated with anagrelide. Out of these patients, 38 had symptoms of thrombosis or hemorrhage and had thrombocytosis resistant to HU. They were then treated with anagrelide at an initial dose of 2.0 mg/day, followed by modifications based upon response and toxicity. In all, 71% of these patients responded with platelet reductions of more than 50% in a median time of approximately 4 weeks. The response rate was not influenced by age, gender, or prior thrombosis or hemorrhage. Importantly, the response rate to anagrelide in patients refractory to prior HU was essentially the same as that of the other 76 CML patients. Treatment with anagrelide was well tolerated and without undue toxicity. Reduction of excessive platelet counts by anagrelide sometimes occurring in CML may lead to the prevention of thrombohemorrhagic complications occurring in this clinical setting and is relevant even in those patients in whom imatinib mesylate is primary therapy.
authors.affiliation: The Leukemia and Myeloproliferative Disease Center, Division of Hematology-Oncology, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA. rtsilve@mail.med.cornell.edu
authors.forename: R T
authors.initials: RT
authors.lastname: Silver
mesh_terms: D000328:Adult; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013922:Thrombocytosis / Q000188:drug therapy*
chemical_list: D011799:Quinazolines; C021139:anagrelide; D006918:Hydroxyurea