微小残留病和IKZF1缺失在预测成人急性B淋巴细胞白血病患者预后中的价值

The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patientswith B-cell acute lymphoblastic leukemia

目的评估微小残留病(MRD)和IKZF1基因缺失在接受儿童特点化疗方案的成人急性B淋巴细胞白血病(B-ALL)中的预后价值。方法回顾性分析2016年1月至2020年9月南方医科大学南方医院收治的149例成人B-ALL患者的预后情况。采用Cox回归模型进行预后因素分析。结果149例患者完全缓解(CR)率为93.2%,5年总生存(OS)率和累积复发率(CIR)分别为(54.3±5.0)%和(47.5±5.2)%。Cox回归分析发现诱导治疗后第45天的微小残留病(MRD3)阳性与患者复发风险独立相关(HR=2.535,95%CI 1.122~5.728,P=0.025),IKZF1基因缺失与患者的死亡风险独立相关(HR=1.869,95%CI 1.034~3.379,P=0.039)。基于MRD3和IKZF1基因状态,我们将149例成人B-ALL患者分为高危组[MRD3阳性和(或)IKZF1基因缺失]和低危组(MRD3阴性且IKZF1基因野生型)。两组的5年OS率分别为(45.5±6.0)%和(69.4±8.6)%(P<0.001),5年CIR分别为(61.6±8.3)%和(25.5±6.5)%(P<0.001),差异均有统计学意义。多因素分析表明,高危组是影响OS(HR=3.937,95%CI 1.975~7.850,P<0.001)以及CIR(HR=4.037,95%CI 2.095~7.778,P<0.001)的独立危险因素。结论MRD结合IKZF1的预后分层系统可更有效地预测成人B-ALL患者的临床结局,有助于指导患者治疗方案的选择。

Objective To reassess the prognostic value of minimal residual disease(MRD)and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia(B-ALL)who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial.Methods We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020.Prognostic factors were identified using Cox regression models.Results The complete remission rate was 93.2%in 149 patients,with a 5-year overall survival(OS)rate of(54.3±5.0)%and a cumulative incidence of relapse(CIR)of(47.5±5.2)%.The Cox regression analysis revealed that MRD positivity at day 45(MRD3)after induction therapy was independently associated with relapse risk(HR=2.535,95%CI 1.122-5.728,P=0.025).Deletion of IKZF1 gene was independently associated with mortality risk(HR=1.869,95%CI 1.034-3.379,P=0.039).Based on MRD3 and IKZF1 gene status,we categorized adult patients with B-ALL into the low-risk(MRD3-negative and IKZF1 gene deletion-negative)and high-risk(MRD3-positive and/or IKZF1 gene wild type)groups.The 5-year OS and CIR rates were(45.5±6.0)%vs(69.4±8.6)%(P<0.001)and(61.6±8.3)%vs(25.5±6.5)%(P<0.001),respectively,in the high-risk and low-risk groups,respectively.The multivariate analysis showed that the high-risk group was an independent risk factor for OS(HR=3.937,95%CI 1.975-7.850,P<0.001)and CIR(HR=4.037,95%CI 2.095-7.778,P<0.001).Conclusion The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL,helping to guide their treatment.