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 (MRD(3)) 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 MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-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.
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（MRD(3)）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MRD(3)和IKZF1基因状态，我们将149例成人B-ALL患者分为高危组[MRD(3)阳性和（或）IKZF1基因缺失]和低危组（MRD(3)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。.
Keywords: Gene, IKZF1; Leukemia, B-cell, acute; Minimal residual disease; Pediatric-inspired regimen therapy.