伊马替尼一线治疗慢性髓系白血病的预后相关因素分析

Prognostic related factors in chronic myeloid leukemia with imatinib as first line treatment

目的:评价生物学因素和治疗相关因素在伊马替尼一线治疗慢性髓系白血病(CML)中的预后价值。方法:回顾性分析72例CML慢性期(CML-CP)患者的临床资料,包括性别、年龄、外周血白细胞计数、血小板计数、嗜碱性粒细胞比例、血红蛋白、脾肋下长度、附加染色体(ACAs)、血清乳酸脱氢酶(LDH)水平、伊马替尼治疗第3个月和第6个月的分子学反应。采用Kaplan-Meier方法分析上述因素对长期生存(OS)率及无事件生存(EFS)率的影响,Cox比例风险模型评估独立预后因素。结果:中位随访期为61(4~96)个月,5年中位OS率88.89%,5年中位EFS率41.67%。单因素分析显示,各组内OS率比较,外周血嗜碱性粒细胞比例<3%的患者明显高于外周血嗜碱性粒细胞比例≥3%的患者(97.1%vs 84.2%,P<0.05);不存在ACAs患者明显高于存在ACAs患者(97.6%vs 28.3%,P<0.05);LDH<1000 U/L患者明显高于LDH≥1000 U/L患者(96.2%vs 84.8%,P<0.05)。各因素组内EFS率比较显示,脾肋下长度<7 cm患者明显高于脾肋下长度≥7 cm患者(41.8%vs 27.0%,P<0.05);不存在ACAs患者明显高于存在ACAs患者(38.4%vs 10.4%,P<0.01);第3个月早期分子学反应(EMR)≤0.1患者明显高于EMR>0.1患者(45.1%vs 16.8%,P<0.01);第6个月EMR<0.1、0.1~0.01、>0.1的3组患者EFS率分别为57.0%、31.8%、15.4%(均P<0.05)。多因素分析显示存在ACAs[OR=5.821,95%CI(2.015,16.819),P<0.01]及治疗第6个月的EMR[OR=4.850,95%CI(2.887,8.148),P<0.01]对EFS率具有独立的预后价值。结论:外周血嗜碱性粒细胞比例、ACAs、LDH可能影响伊马替尼一线治疗CML患者的OS率,脾大小、ACAs、第3、6个月的EMR均会影响患者的EFS率。ACAs和第6个月的EMR对患者EFS率有独立的预后价值。

Objective:To assess the prognostic value of the biological features and therapy related factors in chronic myeloid leukemia(CML)with imatinib as the first line treatment.Methods:A retrospective analysis was performed on 72 cases of CML chronic phase(CML-CP).The data of biological features including sex,age,counts of peripheral white blood cells,platelet count,proportion of peripheral basophilia cells,hemoglobin,proportion of peripheral blast cells,lactic dehydrogenase(LDH),spleen length below the costal margin and additional cytogenetic abnormalities(ACAs),and the data of therapy related factors including the early molecular response(EMR)at 3rd and 6th month after the imatinib treatment were collected.The effects of the factors above on the overall survival(OS)rate and event-free survival(EFS)rate were analyzed by Kaplan-Meier analysis,univariate analysis by Log-rank test and multivariate analysis by COX regression model.Results:During a median follow-up period of 61(4-96)months,the 5-year OS rate was 88.89%,and 5-year EFS rate was 41.67%.Univariate analysis indicated that the OS rate in the patients with proportion of peripheral blast cells<3%was significantly higher than in those≥3%(97.1%vs.84.2%,P<0.05).The OS rate in the patients without ACAs was significantly higher than in those with ACAs(97.6%vs.28.3%,P<0.05).The OS rate in the patients with LDH<1000 U/L was significantly higher than in those with LDH≥1000 U/L(96.2%vs.84.8%,P<0.05).The EFS rate in patients with spleen length below the costal margin<7 cm was significantly higher than in those with≥7 cm(41.8%vs.27.0%,P<0.05),that in the patients without ACAs was significantly higher than in those with ACAs(38.4%vs.10.4%,P<0.01),that in the patients with the 3rd-month EMR≤0.1 was significantly higher than in those with the 3rd-month EMR>0.1(45.1%vs.16.8%,P<0.01).The EFS rate in the patients with EMR<0.1,0.1-0.01 and>0.1 at 6th month was 57.0%,31.8%and 15.4%respectively(all P<0.05).The multivariate analysis showed that patients with ACAs[OR=5.821,95%CI(2.015,16.819),P<0.01]and worse EMR at the 6th month[OR=4.850,95%CI(2.887,8.148)]were independent poor prognostic factors.Conclusion:Proportion of peripheral blast cells,ACAs and LDH may influence the OS rate of patients with CML with imatinib as first-line treatment,and the size of spleen,ACAs,the EMR at 3rd and 6th month can affect the EFS rate.ACAs and the EMR at 6th month had independent prognostic value.