目的:探讨尼洛替尼治疗伊马替尼耐药的慢性髓系白血病(CML)的疗效及安全性。方法:收集伊马替尼治疗失败而接受尼洛替尼治疗的10例患者,其中慢性期7例,加速期2例,急变期1例。接受伊马替尼治疗的平均时间为36.7个月,停用原因为丧失疗效或未达主要分子学反应(MMR)7例、进展至加速期或急变期2例、原发性耐药1例。4例患者检测出5个点突变,其中1例慢性期患者检出2个突变点。10例患者接受尼洛替尼的剂量均为400mg q12h,每个月复查血常规,每3个月监测细胞遗传学及分子生物学缓解情况(FISH及RQ-PCR法),定期监测肝肾功能、胰酶、电解质及心电图等,并记录有无皮疹、头痛等不良反应。结果:10例患者接受尼洛替尼治疗的平均时间为12.5(3～30)个月。8例获得主要遗传学反应以上疗效,其中5例获得完全细胞遗传学反应,3例获得MMR。2例加速期患者中,1例恢复至慢性期并持续获得MMR,1例死亡。1例急单变患者(Ph+伴附加染色体异常)获部分细胞遗传学反应后丧失疗效,最终死亡。不良反应依次为轻度皮疹6例、胆红素升高3例、转氨酶升高2例、头痛1例、血糖升高1例及3/4级血液学不良反应1例。结论:尼洛替尼结合ABL激酶的效价更高,选择性更强,能抑制除T315I、Y253H、F359V/C及E255K/V以外的致伊马替尼耐药的点突变,且不良反应少,可用于伊马替尼耐药及不耐受的慢性期或加速期CML。 Objective: To investigate the efficacy and safety of nilotinib in the treatment of imatinib-resistant chronic myeloid leukemia (CML). METHODS: Ten patients with failed imatinib treatment and nilotinib treatment were collected, including 7 in the chronic phase, 2 in the accelerated phase, and 1 in the blast phase. The average duration of treatment with imatinib was 36.7 months. The reason for the discontinuation was loss of efficacy or failure to reach the major molecular response (MMR) in 7 cases, progression to accelerated or blast crisis in 2 cases, and primary drug resistance in 1 case. . Four point mutations were detected in four patients, and one of them detected two mutations in the chronic phase. Ten patients received nilotinib at a dose of 400 mg q12h. Blood was reviewed every month. Cytogenetics and molecular biological response (FISH and RQ-PCR) were monitored every 3 months. Hepatorenal function was monitored regularly. , trypsin, electrolytes, electrocardiogram, etc., and recorded no rash, headache and other adverse reactions. RESULTS: The average time for 10 patients receiving nilotinib was 12.5 (3 to 30) months. In 8 cases, the above genetic response was achieved, of which 5 cases had complete cytogenetic response and 3 cases received MMR. Of the 2 accelerated patients, 1 recovered to the chronic phase and sustained MMR, and 1 died. One case of acutely mutated patients (Ph+ with additional chromosomal abnormalities) lost some of the cytogenetic response and eventually died. Adverse reactions included 6 cases of mild rash, 3 cases of bilirubin elevation, 2 cases of elevated transaminases, 1 case of headache, 1 case of elevated blood glucose, and 1 case of grade 3/4 hematologic adverse reactions. CONCLUSION: Nilotinib binds to ABL kinase with higher potency and selectivity, and it can inhibit the imatinib-resistance point mutations other than T315I, Y253H, F359V/C and E255K/V, and adverse reactions. Less, it can be used for imatinib resistance and intolerance in chronic or accelerated CML.