Trapp O M, Beykirch M K, Petrides P E
Department of Medicine III, University School of Medicine Grosshadern, Munich, Germany.
Blood Cells Mol Dis. 1998 Mar;24(1):9-13. doi: 10.1006/bcmd.1998.0166.
Chronic myelogenous leukemia (CML) is usually treated with hydroxyurea or interferon-alpha. In some patients high platelet counts develop although leukocyte counts are well controlled with these drugs. If in such a situation cytoreductive therapy has to be intensified by a increase of the dosage, anemia and leukocytopenia as well as adverse effects of the drugs are likely to occur. In twelve CML patients we have therefore combined the basic CML treatment with anagrelide. This drug which selectively reduces platelet counts has been shown to be efficacious in the control of thrombocytosis in essential thrombocythemia. The diagnosis had been confirmed in all CML patients by cytogenetic and/or molecular biological analysis. The median age of our group was 58 years. Five were women and seven men. All patients were on treatment with hydroxyurea, some of them had previously received treatment with interferon-alpha (alone or in combination with hydroxyurea), busulfan or melphalan. Prior to the initiation of anagrelide treatment the platelet count was between 970,000 and 3,600, 000/microl (median about 2,000,000/microl). Seven patients had thrombohemorrhagic complications. All twelve patients, experienced hematologic responses, since their platelet counts decreased to less than 600,000/microl. The median platelet count after reduction was 343,000/microl. The median dosage required to achieve these responses and to maintain them for a period of at least four weeks was 1.9 mg/day. Thrombohemorrhagic complications disappeared or did not recur in all symptomatic patients. Adverse effects were seen in 3/12 patients: headache (1), tachycardia (1), palpitation (1) and fluid retention (1). Whereas these symptoms were mild and transitory they caused one patient to request discontinuation of treatment. Currently five patients are still on treatment with anagrelide (median duration of treatment 11 months) while therapy had to be discontinued in the seven others because of bone marrow transplantation, development of osteomyelofibrosis, blast crisis or on patient request. In our experience anagrelide is a useful therapeutic adjunct when thrombocytosis in patients with CML cannot properly controlled alone with traditional drugs.
慢性粒细胞白血病（CML）通常采用羟基脲或α干扰素进行治疗。在一些患者中，尽管使用这些药物能很好地控制白细胞计数，但血小板计数仍会升高。如果在这种情况下必须通过增加剂量来强化细胞减灭治疗，可能会出现贫血、白细胞减少以及药物的不良反应。因此，我们对12例慢性粒细胞白血病患者将基本的慢性粒细胞白血病治疗与阿那格雷联合使用。这种能选择性降低血小板计数的药物已被证明在控制原发性血小板增多症的血小板增多方面有效。所有慢性粒细胞白血病患者均通过细胞遗传学和/或分子生物学分析确诊。我们组患者的中位年龄为58岁。其中5名女性，7名男性。所有患者均接受羟基脲治疗，部分患者此前曾接受过α干扰素（单独或与羟基脲联合）、白消安或美法仑治疗。在开始使用阿那格雷治疗前，血小板计数在970,000至3,600,000/微升之间（中位值约为2,000,000/微升）。7例患者有血栓出血并发症。所有12例患者均出现血液学反应，因为他们的血小板计数降至低于600,000/微升。血小板计数降低后的中位值为343,000/微升。达到这些反应并维持至少四周所需的中位剂量为1.9毫克/天。所有有症状的患者血栓出血并发症均消失或未复发。3/12的患者出现了不良反应：头痛（1例）、心动过速（1例）、心悸（1例）和液体潴留（1例）。尽管这些症状轻微且短暂，但仍有1例患者要求停药。目前有5例患者仍在接受阿那格雷治疗（中位治疗持续时间为11个月），而其他7例患者因骨髓移植、骨髓纤维化发展、急变期或患者要求而不得不停药。根据我们的经验，当慢性粒细胞白血病患者的血小板增多症无法仅用传统药物得到适当控制时，阿那格雷是一种有用的治疗辅助药物。
