Silver R T
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.
Leukemia. 2005 Jan;19(1):39-43. doi: 10.1038/sj.leu.2403556.
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.
我们报告了口服盐酸阿那格雷治疗38例伴有慢性粒细胞白血病（CML）的羟基脲（HU）耐药性血小板增多症患者的II期试验结果。在一项针对400多名患有四种骨髓增殖性疾病之一（原发性血小板增多症、真性红细胞增多症、特发性骨髓纤维化和CML）的患者的II期研究中，阿那格雷的疗效得到了充分证实。在最后一个亚组中，有114例CML伴显著血小板增多症患者接受了阿那格雷治疗。在这些患者中，38例有血栓形成或出血症状，且对HU耐药。然后他们接受阿那格雷治疗，初始剂量为2.0毫克/天，随后根据反应和毒性进行调整。总体而言，这些患者中有71%在大约4周的中位时间内血小板减少超过50%，从而产生反应。反应率不受年龄、性别或既往血栓形成或出血的影响。重要的是，对先前HU难治的患者对阿那格雷的反应率与其他76例CML患者基本相同。阿那格雷治疗耐受性良好，无过度毒性。阿那格雷降低CML患者有时出现的过高血小板计数，可能有助于预防该临床情况下发生的血栓出血并发症，即使在那些以甲磺酸伊马替尼作为一线治疗的患者中也是如此。
