伊马替尼治疗慢性粒细胞白血病135例远期疗效观察

Investigation of long-term follow-up results of 135 patients with chronic myeloid leukemia receiving imatinib

目的 对伊马替尼治疗慢性粒细胞白血病（CML）的疗效及安全性进行分析,并初步探讨影响CML患者生存的因素.方法 135例CML患者应用伊马替尼治疗,监测其血常规、染色体核型、bcr-abl p210转录本表达及不良反应.结果 中位随访20（3～67）个月.慢性期患者累积获得的完全血液学缓解（CHR）率为97.9%,主要细胞遗传学缓解（MCyR）率为78.3%,完全细胞遗传学缓解（CCyR）率为72.2%,完全分子学缓解（CMoR）率为35.1%,均显著高于加速期及急变期（P＜0.001）.慢性期低危组与高危组之间CCyR率有差异（P=0.048）.慢性期患者1、3和5年总生存（OS）率分别为：（97.8±1.5）%、（95.2±2.4）%、（91.9±3.2）%,疾病无进展生存（PFS）率分别为（92.6±2.7）%、（85.5±3.7）%、（81.3±4.3）%;加速期患者6个月、1、2年OS率分别为：（93.8±6.1）%、（72.5±11.8）%、（64.5±12.9）%,PFS率分别为：（92.3±7.4）%、（64.5±14.7）%、（53.7±15.7）%;急变期患者6、12、19个月OS率分别为：（86.4±7.3）%、（45.4±11.4）%、（19.4±9.8）%,PFS率分别为：（70.1±12.6）%、（37.6±15.6）%、（18.8±15.4）%.慢性期达到CMoR、CCyR的患者与仅达CHR者PFS及OS比较差异均有统计学意义（P≤0.001）;多因素分析显示：耐药是影响慢性期患者PFS（P=0.000,RR=46.744）及OS（P=0.007,RR=20.270）的因素.伊马替尼口服非血液学毒性较轻,患者多可耐受;血液学毒性是减量或停药的主要原因.结论 伊马替尼治疗CML慢性期疗效显著优于加速期及急变期;慢性期患者达到CCyR甚至CMoR是获得长期生存的关键,伊马替尼耐药是伊马替尼治疗CML面临的主要问题.

Objective To evaluate the efficacy and safety of imatinib in chronic myeloid leukemia （CML） patients and analyse the factors affecting the survival. Methods 135 CML patients receiving imatinib were evaluated for hematologic, cytogenetic, and molecular responses and adverse events. Results The median follow-up was 20 （range 3-67） months. The rate of cumulative complete hematological response （CHR）, major cytogenetic response （MCyR）, complete cytogenetic response（ CCyR ） and complete molecular response （CMoR） in chronic phase CML patients were 97.9 %, 78.3 %, 72.2 % and 35.1%, respectively.These rates were significantly higher in chronic phase than in accelerated phase and blastic phase （P 〈0.001）.The rate of CCyR in low-risk patients was significantly higher than high-risk patients （P =0.048）. The estimated overall survival （OS） rate at 1, 3 and 5 year for chronic phase patients were （97.8±1.5） %, （95.2±2.4） % and （91.9±3.2） %, respectively. The estimated progression-free （PFS） survival rate at 1, 3 and 5 year were （92.6±2.7） %, （85.5±3.7） % and （81.3±4.3） %, respectively. The OS rate for accelerated phase patients at 6, 12 and 24 month were （93.8±6.1） %, （72.5±11.8） % and （64.5±12.9） %, the PFS rate were （92.3±7.4） %,（64.5±14.7） %, （53.7±15.7） %, respectively. The OS rate for blastic phase patients at 6, 12 and 19 month were （86.4±7.3） %, （45.4±11.4） %, （19.4±9.8） %, the PFS rate were （70.1±12.6） %, （37.6±15.6） % and （18.8±15.4） %, respectively. The OS and PFS of patients in chronic phase who achieved CCyR or CMoR were better than patients only achieved CHR （P ≤0.001）. Multivariate analysis for survival of chronic phase patients indicated that imatinib resistance was the unfavourable factor for PFS （P =0.000, RR =46.744） and OS（P =0.007, RR =20.270）. The non-hematological toxicity of imatinib was slight and tolerable, severe hematological toxicity was the major reason for dose reduction or drug discontinuation. Conclusion The efficacy of imatinib in chronic phase CML patients is significantly superior to which in accelerated phase and blastic phase; Achieving CCyR even CMoR is the most important thing for longer survival, iinatinib resistance is the major problem in the treatment with imatinib.