二代酪氨酸激酶抑制剂一线、二线治疗慢性髓细胞白血病的临床研究

A clinical study on second-generation tyrosine kinase inhibitors as first-and second-line treatments in chronic myeloid leukemia

目的探讨二代络氨酸激酶抑制剂（tyrosine kinase inhibitors，TKI）一线、二线治疗慢性髓细胞白血病（chronic myelocytic leukemia，CML）的临床价值。方法收集2008年2月-2012年3月于我院接受二代TKI治疗的56例CML患者的临床资料，其中20例接受达沙替尼一线治疗（一线组），36例接受达沙替尼二线治疗（二线组），既往接受伊马替尼一线治疗54例，对伊马替尼耐药51例，不耐受3例；其余2例曾接受除伊马替尼以外治疗），记录患者治疗反应性及安全性。结果①慢性期治疗3个月26例（86．67％）达到CHR，15例（50．00％）CCyR，15例（50．00％）PCyR，治疗12个月4例（13．33％）获得CMR，15例（30．00％）获得MMR；加速期治疗3个月8例（80．00％）获得CHR，治疗12个月无1例获得CyR，治疗12个月，2例（20．00％）获得MMR，1例（10．00％）获得CMR；急变期治疗12个月无1例获得CyR、MMR，治疗3个月6例（37．50％）获得CHR，1例（6．25％）获得CMR，治疗12个月1例（6．25％）获得CMR；②一线组随访CHR、CMR率均高于二线组，但其达CHR、CMR时间较二线组长（P〈O．05）；③一线、二线治疗各不良反应发生率比较差异无统计学意义（P〉0．05）；④慢性期患者OS、中位生存期高于加速期与急变期，加速期OS又高于急变期（P〈0．05），TKI一、二线治疗CML患者OS、中位生存期对比差异无统计学意义（P〉0．05）。结论二代TKI达沙替尼一、二线治疗CML均可获取肯定的血液学反应、细胞遗传学反应及分子生物学反应，且以慢性期患者疗效最佳，OS最长，同时安全性肯定。

Objective To determine the clinical value of second-line tyrosine kinase inhibitors （TKIs） in the treatment of chronic myeloid leukemia （CML）. Methods The clinical data of 56 CML patients who received second-generation TKI treatment in our hospital from February 2008 to March 2012 were collected. Among them, 20 patients received dasatinib as first-line treatment （first-line group） and 36 as second-line treatment （second-line group）. Of 54 patients who had received first-line imatinib treatment, 51 became imatinib-resistant and 3 became imatinib intolerant. The remaining 2 patients had received treatments other than imatinib. Patient response and drug safety were recorded. Results （1） Among patients in the chronic phase, 26 patients （86.67%） achieved CHR, 15 （50.00%） achieved CCyR, and 15 （50.00%） achieved PCyR at 3 months of treatment; 4 （13.33%） achieved CMR and 15 achieved （30.00%） MMR at 12 months of treatment. Among patients in accelerated disease, 8 （80.00%） achieved CHR at 3 months of treatment; none achieved CyR, 2 cases （20.00%） achieved MMR, and 1 （10.00%） achieved CMR at 12 months of treatment. Among patients in the blastic phase, CyR and MMR were not achieved at 12 months of treatment; 6 （37.50%） achieved CHR and 1 （6.25%） achieved at 3 months of treatment; 1 （6.25%） achieved CMR at 12 months of treatment. （2） During the follow-up, the first-line group had higher CHR and CMR rates than those in the second-line group, but also experienced longer time to achieve CHR and CMR compared with the second-line group （P〈0.05）. （3） There was no significant difference in the incidence of the adverse reactions between the first-line and second-line groups （P〉0.05）. （4） Patients in chronic phase had longer median OS and median survival time than those in accelerated phase and the blastic phase. Patients in accelerated phase had longer OS than those in blastic phase （P〈0.05）. There was no significant differences in OS, median survival time between TKI first-line and second-line treatments among CML patients （P〉0.05）. Conclusion The TKI dasatinib either as first-or second-line treatment of CML may lead to definite responses in hematology, cytogenetics and molecular biology. Patients in chronic phase may benefit from the treatment with best outcomes, longest OS and with good safety.