CAJ | 학술논문

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.
목적 대이마체니치료만성립세포백혈병(CML)적료효급안전성진행분석,병초보탐토영향CML환자생존적인소.방법 135례CML환자응용이마체니치료,감측기혈상규、염색체핵형、bcr-abl p210전록본표체급불량반응.결과 중위수방20(3～67)개월.만성기환자루적획득적완전혈액학완해(CHR)솔위97.9%,주요세포유전학완해(MCyR)솔위78.3%,완전세포유전학완해(CCyR)솔위72.2%,완전분자학완해(CMoR)솔위35.1%,균현저고우가속기급급변기(P＜0.001).만성기저위조여고위조지간CCyR솔유차이(P=0.048).만성기환자1、3화5년총생존(OS)솔분별위:(97.8±1.5)%、(95.2±2.4)%、(91.9±3.2)%,질병무진전생존(PFS)솔분별위(92.6±2.7)%、(85.5±3.7)%、(81.3±4.3)%;가속기환자6개월、1、2년OS솔분별위:(93.8±6.1)%、(72.5±11.8)%、(64.5±12.9)%,PFS솔분별위:(92.3±7.4)%、(64.5±14.7)%、(53.7±15.7)%;급변기환자6、12、19개월OS솔분별위:(86.4±7.3)%、(45.4±11.4)%、(19.4±9.8)%,PFS솔분별위:(70.1±12.6)%、(37.6±15.6)%、(18.8±15.4)%.만성기체도CMoR、CCyR적환자여부체CHR자PFS급OS비교차이균유통계학의의(P≤0.001);다인소분석현시:내약시영향만성기환자PFS(P=0.000,RR=46.744)급OS(P=0.007,RR=20.270)적인소.이마체니구복비혈액학독성교경,환자다가내수;혈액학독성시감량혹정약적주요원인.결론 이마체니치료CML만성기료효현저우우가속기급급변기;만성기환자체도CCyR심지CMoR시획득장기생존적관건,이마체니내약시이마체니치료CML면림적주요문제.
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.