【作者】 王爽；

【导师】 王晓雪；

【作者基本信息】 中国医科大学 ， 内科学（专业学位）， 2025， 硕士

【摘要】 目的:本研究旨在比较JALSG-ALL202-O方案与CALLG2008方案在新诊断Ph-ALL患者中的疗效与安全性,为Ph-ALL患者选择合适的诊治方案提供参考依据。同时通过对临床数据的分析,明确影响我中心Ph-ALL患者预后的危险因素。研究方法:本课题回顾性收集2019年4月至2024年7月于中国医科大学附属第一医院确诊为Ph-ALL的99例患者数据,收集患者的性别、年龄、血常规、骨髓细胞形态学检测结果、流式细胞学检测结果、染色体核型分析检测结果、基因突变检测结果、融合基因检测结果、不良反应和治疗方案。本研究采用SPSS 26.0进行统计学分析。分类变量以频数(百分比)表示,组间差异比较采用卡方检验(χ2)或Fisher精确检验;连续变量以均值±标准差或中位数(四分位间距)描述。生存结局通过Kaplan-Meier法评估,组间生存差异采用Log-rank检验进行单因素分析,多因素Cox比例风险回归模型用于识别独立预后因素。所有分析采用双侧检验,显著性水平设定为α=0.05(P<0.05判定为差异具有统计学意义)。结果:1、可纳入生存分析的85例患者总体中位随访时间17.28个月,中位OS为27.79个月(95%CI:16.82～38.76),中位EFS为13.8个月(95%CI:5.93～21.67),3年OS率为40.5%,3年EFS率为32.5%。2、有29例患者接受JALSG-ALL202-O方案治疗,70例患者接受CALLG2008方案治疗,两组患者的基线特征无显著性差异。两组诱导缓解率差异无统计学意义(100%vs 91.5%,P=0.171),诱导治疗后CMR率差异无统计学意义(64.3%vs 46.6%,P=0.123)。3年OS率差异无统计学意义(50.8%vs 35.8%,P=0.147),3年EFS率差异有统计学意义(41.2%vs 27.8%,P=0.028)。CALLG2008方案组诱导治疗期间有4例患者死亡,均与重症感染有关。JALSG-ALL202-O方案无诱导治疗期间死亡患者。JALSG-ALL202-O方案组共有6人出现疾病复发,CALLG2008方案共有25人出现疾病复发,差异具有统计学意义(21.4%vs 50%,P=0.013)。3、在总体患者中,单因素预后分析显示,未移植和MRD持续状态显著降低患者OS,患者年龄>40岁、免疫表型为B-ALL和未移植显著降低EFS(均P<0.05)。多因素Cox回归分析显示MRD持续状态是影响OS的独立不良预后因素(HR=2.509,P=0.01),初诊高白细胞计数(B≥50×10~9/L、T≥100×10~9/L)是影响EFS的独立不良预后因素(HR=0.480,P=0.046)。亚组分析表明,非移植患者中免疫表型为Pro-B-ALL、具有高危遗传特征、初次诱导治疗后未达CR和MRD持续状态是影响OS的不良预后因素,免疫表型为B-ALL、具有高危遗传学特征是影响EFS的不良预后因素。其中MRD持续状态是影响OS的独立不良预后因素(HR=4.075,P=0.009)。4、JALSG-ALL202-O方案组和CALLG2008方案组主要的不良反应有口腔黏膜损伤65.5%、28.5%,呼吸道感染48.3%、45.7%,腹泻44.8%、38.6%,肛周感染6.9%、8.6%,败血症17.2%、25.7%,真菌感染20.7%、21.4%,转氨酶升高58.6%、45.7%,呕吐24.1%、25.7%,凝血异常58.6%、48.6%,肾功能不全20.6%、7.1%,IV级骨髓抑制48.3%、51.4%,末梢神经炎10.3%、11.4%,其中JALSG-ALL202-O方案组中口腔感染(P=0.001)、肾功能不全(P=0.007)比例显著高于CALLG2008方案组,但两组均未发生治疗相关死亡。结论:1、JALSG-ALL202-O方案对比CALLG2008方案治疗初治成人ALL完全缓解率和总生存率相当,但无事件生存率高,复发率低。2、患者MRD持续状态是影响OS的独立不良预后因素,具有高白细胞是影响EFS的独立不良预后因素。3、JALSG-ALL202-O方案与CALLG2008方案安全性可控,无化疗相关的致死性不良反应。更多还原

【Abstract】 Objective:To compare the efficacy and safety of the JALSG-ALL202-O regimen versus the CALLG2008 regimen in newly diagnosed Ph-ALL patients,providing a reference for treatment selection.Additionally,we aimed to identify prognostic risk factors for Ph-ALL patients at our center through clinical data analysis.Methods:This retrospective study included 99 Ph-ALL patients diagnosed at the First Affiliated Hospital of China Medical University from April 2019 to July 2024.Data collected included gender,age,blood tests,bone marrow morphology,flow cytometry,karyotype analysis,gene mutations,fusion genes,adverse events,and treatment regimens.Statistical analysis was performed using SPSS 26.0.Categorical variables were expressed as frequencies(percentages),with group comparisons using chi-square or Fisher’s exact tests.Continuous variables were described as mean±standard deviation or median(interquartile range).Survival outcomes were assessed using Kaplan-Meier analysis,with group differences evaluated by log-rank test.Multivariate Cox regression was used to identify independent prognostic factors.A two-sided significance level ofα=0.05 was applied.Results:1.Among the 85 patients eligible for survival analysis,the median follow-up was40.64 months(95%CI:34.37-43.7).Median OS was 27.79 months(95%CI:16.82-38.76),with a 3-year OS rate of 40.5%(95%CI:28.5%-52.5%).Median EFS was13.8 months,with a 3-year EFS rate of 32.5%(95%CI:21.1%-43.9%).2.Twenty-nine patients received the JALSG-ALL202-O regimen,and 70 received the CALLG2008 regimen.Baseline characteristics were comparable.No significant differences were observed in induction remission rates(100%vs.91.5%,P=0.171)or CMR rates(64.3%vs.46.6%,P=0.123).The 3-year OS rate was 50.8%vs.35.8%(P=0.147),while the 3-year EFS rate was 41.2%vs.27.8%(P=0.028),showing a significant difference.Four deaths occurred during induction in the CALLG2008 group,all related to severe infections,while no deaths occurred in the JALSG-ALL202-O group.Relapse rates were significantly lower in the JALSG-ALL202-O group(21.4%vs.50%,P=0.013).3.Univariate analysis identified non-transplantation and persistent MRD as significant predictors of reduced OS.Age>40 years,B-ALL immunophenotype,and non-transplantation were associated with reduced EFS(P<0.05).Multivariate Cox analysis showed persistent MRD as an independent adverse prognostic factor for OS(HR=2.509,P=0.01),and high initial white blood cell count(B≥50×10~9/L,T≥100×10~9/L)as an independent adverse factor for EFS(HR=0.480,P=0.046).Subgroup analysis in non-transplant patients identified Pro-B-ALL immunophenotype,high-risk genetic features,failure to achieve CR after induction,and persistent MRD as adverse prognostic factors for OS,while B-ALL immunophenotype and high-risk genetic features were adverse for EFS.Persistent MRD was an independent adverse factor for OS(HR=4.075,P=0.009).4.Common adverse events in both groups included oral mucositis(65.5%vs.28.5%),respiratory infections(48.3%vs.45.7%),diarrhea(44.8%vs.38.6%),and grade IV myelosuppression(48.3%vs.51.4%).The JALSG-ALL202-O group had higher rates of oral infections(P=0.001)and renal dysfunction(P=0.007),indicating both regimens were generally safe.Conclusions:1.The JALSG-ALL202-O regimen showed comparable complete remission and overall survival rates to CALLG2008 but demonstrated superior EFS and lower relapse rates.2.Persistent MRD was an independent adverse prognostic factor for OS,while high white blood cell count was an independent adverse factor for EFS.3.Both regimens were safe,with no treatment-related fatal adverse events.更多还原