摘要目的 分析费城染色体阳性急性淋巴细胞白血病(Ph+ALL)成年患者诱导治疗的疗效与预后影响因素.方法 选择2013年11月至2018年11月山西医科大学第二医院血液科收治的52例初诊Ph+ALL患者为研究对象.根据诱导治疗方法的不同,将其分为化疗联合酪氨酸激酶抑制剂(TKI)组(n=33)和单纯化疗组(n=19).采用回顾性分析方法,收集52患者的完全缓解(CR)率、未完全缓解(NR)率、复发率、总体预后,以及分析Ph+ALL成年患者预后的影响因素.随访时间截至2018年11月30日.2组患者CR率的组间比较采用χ2检验.采用Kaplan-Meier法进行生存分析.采用Log-rank检验对不同性别、年龄与肝、脾大及白细胞计数等预后影响因素进行单因素分析.将单因素分析结果中有统计学意义,以及有临床指导意义的影响因素,纳入Cox比例风险回归模型进行多因素分析.本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求,所有患者在治疗前均被告知病情及可能出现的不良反应,与患者常规签署化疗知情同意书.结果 ① 本研究52例初诊Ph+ALL患者接受4周诱导治疗后,获得CR患者为36例(69.2％),NR者为16例(30.8％).4周诱导治疗后,化疗联合TKI组患者的CR率为83.3％(30/33),高于单纯化疗组的16.7％(6/19),并且差异有统计学意义(χ2=17.237,P<0.001).②本研究52例Ph+ALL患者的复发率为69.2％(36/52),中位复发时间为9个月(1～49个月).③本研究52例Ph+ALL患者截至随访结束,中位生存时间为11个月(4～52个月),1年总体生存(OS)率为42.3％,1年无事件生存(EFS)率为32.8％.④单因素分析结果显示,联合使用TKI患者的中位EFS率和OS率分别为11.0％(95％CI:9.3％ ～12.7％)和11.0％(95％CI:10.1％ ～11.8％),高于未联合使用TKI者的6.0％(95％CI:5.0％～7.0％)和9.0％(95％CI:7.6％～10.4％),并且差异均有统计学意义(χ2=19.021,P<0.001;χ2=11.894,P<0.001).诱导化疗4周达CR患者的中位EFS率和OS率分别为10.0％(95％CI:7.7％～12.4％)和11.0％(95％CI:10.3％～11.9％),高于未达CR者的6.0％(95％CI:4.7％～7.3％)和9.0％(95％CI:7.0％ ～11.0％),并且差异亦均有统计学意义(χ2=15.447,P<0.001;χ2=11.139,P=0.001).⑤Cox多因素分析结果显示,联合使用TKI是Ph+ALL患者EFS率(HR=0.370,95％CI:0.157～0.872,P=0.023)和OS率(HR=0.321,95％CI:0.156～0.660,P=0.002)的独立保护因素.结论 Ph+ALL成年患者诱导治疗中联合使用TKI,可能提高患者诱导治疗疗效,改善患者预后.

abstractsObjective To explore the efficacy and prognostic factors of induction therapy in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).Methods From November 2013 to November 2018,a total of 52 newly diagnosed adult patients with Ph+ ALL who admitted to the Department of Hematology,Second Hospital of Shanxi Medical University were included in this study.According to different induction treatment regimens,they were divided into chemotherapy combined with tyrosine kinase inhibitor (TKI)group (n =33)and chemotherapy alone group (n =19).Retrospective analysis method was used to collect the complete remission (CR)rate,no complete remission (NR)rate, recurrence rate,prognosis,and the influencing factors of prognosis in adult patients with Ph+ ALL.The chi-square test was used to compare the CR rates between two groups.The Kaplan-Meier method was used to draw the survival curves.Univariate analysis was performed by Log-rank test to determine the influencing factors affecting the prognosis of patients,such as gender,age,hepatosplenomegaly and white blood cell count and so on.Statistically significant factors and factors with clinical guiding significance in the univariate analysis were included in the Cox proportional hazard regression model for multivariate analysis.The follow-up period was up to November 30,2018.The procedure of this study was accordance with the requirement of the revised World Medical Association Declaration of Helsinki in 2013.Informed consent was obtained from all participants.Results ① Among the 52 patients with newly diagnosed Ph+ ALL,36 patients (69.2％)achieved CR and 16 patients (30.8％)achieved NR after 4 weeks induction therapy.The CR rate was 83.3％ (30/33)in the chemotherapy combined with TKI group,which was higher than that of 16.7％(6/19)in the chemotherapy alone group,and the difference was statistically significant (χ2 =17.237,P <0.001).② The recurrence rate of the 52 patients in this study was 69.2％ (36/52),and the median time to recurrence was 9 months (1-49 months).③ The median survival time of the 52 patients in this study was 11 months (4-52 months),the 1-year overall survival (OS)rate was 42.3％,and the 1-year event-free survival (EFS)rate was 32.8％.④ Results of univariate analysis showed that the median EFS rate and OS rate of patients with TKI were 11.0％ (95％ CI : 9.3％-12.7％) and 11.0％ (95％ CI : 10.1％-11.8％), respectively,which were higher than those of 6.0％ (95％CI :5.0％-7.0％)and 9.0％ (95％CI :7.6％-10.4％)in patients without TKI,and the differences were statistically significant (χ2 =19.021,P <0.001;χ2 = 11.894,P < 0.001 ).The median EFS rate and OS rate of CR patients after 4 weeks induction chemotherapy were 10.0％ (95％CI :7.7％-12.4％)and 11.0％ (95％CI :10.3％-11.9％),respectively, which were higher than those of 6.0％ (95％CI :4.7％-7.3％)and 9.0％ (95％CI :7.0％-11.0％)in NR patients,the differences were also statistically significant (χ2 =15.447,P <0.001;χ2 =11.139,P =0.001).⑤ Cox multivariate analysis showed that combination of TKI was an independent protective factor for EFS rate (HR =0.370,95％CI :0.157-0.872,P =0.023)and OS rate (HR =0.321,95％CI :0.156-0.660,P =0.002)in adult patients with Ph+ ALL.Conclusions The combination of TKI in the induction therapy of adult patients with Ph+ ALL may improve the therapeutic effect of patients and improve the prognosis of them.