尼罗替尼治疗对伊马替尼耐药或不耐受的慢性粒细胞白血病临床分析

Nilotinib treatment for imatinib resistant or intolerant chronic myelogenous leukemia

目的评价对伊马替尼耐药或不耐受的慢性粒细胞白血病（CML）患者接受尼罗替尼治疗的安全性和疗效。方法35例对伊马替尼耐药或不耐受CML患者接受尼罗替尼治疗，400mg，口服，每日2次，评估其疗效、不良反应、总体生存和疾病进展情况。结果35例对伊马替尼耐药或不耐受的CML患者，中位尼罗替尼治疗时间11个月，中位随访时间19个月。尼罗替尼治疗相关的非血液学不良反应多为1～2级，主要为胆红素升高（76％）和皮疹（46％）。3～4级血液学不良反应包括血小板减少（37％）、中性粒细胞减少和贫血（均为26％）。患者大多可耐受。进展期（包括加速期和急变期）患者的3～4级血液学不良反应发生率明显高于慢性期。35例接受尼罗替尼治疗的患者中，CML慢性期患者获得主要细胞遗传学缓解率为38．5％，明显高于进展期患者（22．2％）。达主要细胞遗传学缓解的中位时间为3个月。进展期患者发生疾病进展的比例明显高于慢性期。18个月预期总体生存率为（93．5±1．0）％。结论尼罗替尼为对伊马替尼耐药和不耐受的CML患者提供了一个有效并安全的治疗手段。尼罗替尼治疗慢性期CML更为安全和有效。

Objective To evaluate the safety and efficacy of nilotinib in chronic myelogenous leukemia （CML） patients with resistance or intolerance to imatinib. Methods Thirty-five CML patients after imatinib failure or intolerance received oral administration of 400 mg nilotinih twice daily. The overall survival, hematologic and cytogenetic responses, as well as adverse events were evaluated. Results The median duration of nilotinib therapy was 11 （ 1 - 23 ） months, with a median follow-up of 19 months. Nonhematologic adverse events were mostly of grade 1 - 2. The most common ones possibly related to nilotinib were increase of bilirubin （76%） and rash （46%）. Grade 3 -4 hematologic adverse events includes thromboeytopenia （37%）, neutropenia （26%） and anemia （26%）. Nilotinib was proved to be well-tolerated in this study. Grade 3 - 4 hematologic adverse events happened more frequently in advanced phase CML. The rate of major cytogenetie response in chronic phase（CP） CML was much higher than those in advanced CML （38.5% vs 22.2% ）. The median time to major cytogenetic response was 3 months. The estimated overall survival at 18 months was （93.5 ± 1.0） %. Conclusion Nilotinib is a more effective and safe treatment option for imatinib-resistant or -intolerant CML-CP patients.