树突状细胞疫苗联合细胞因子诱导的杀伤细胞在中危急性髓系白血病维持治疗中的疗效研究

Clinical outcomes of dendritic cell vaccine combined with cytokine-induced killer in maintenance therapy for intermediate‑risk acute myeloid leukemia

  • 摘要: 背景 中危急性髓系白血病(acute myeloid leukemia,AML)患者即使通过化疗或自体移植(autologous stem cell transplantation,ASCT)等巩固治疗手段达到微小残留病(minimal residual disease,MRD)阴性,2 年累积复发率(cumulative incidence of relapse,CIR)仍高达30% ~ 50%,现有维持治疗方案难以兼顾有效性与安全性。目的 探索基因修饰树突状细胞(genetically modified dendritic cell,gmDC)疫苗联合细胞因子诱导的杀伤细胞(cytokine-induced killer,CIK)用于中危AML患者维持治疗的长期疗效及安全性。方法 采用回顾性队列设计,纳入2013 年1 月至2023 年12 月于我院治疗的中危AML患者,入组患者均在巩固化疗后达到MRD阴性。根据后续治疗方式分为gmDC疫苗联合CIK维持治疗组(gmDC组)和常规随访观察组(对照组)。研究的主要终点为总生存期(overall survival,OS),关键次要终点包括无进展生存期(progression-free survival,PFS)和CIR,次要终点为安全性。结果 本研究共纳入23 例中危AML患者,其中gmDC组13 例,对照组10 例。两组中位年龄分别为34(16 ~ 83)岁和43(19 ~ 62)岁,男性比例分别为46.2%和40.0%,差异均无统计学意义(P>0.05);除ASCT外(gmDC组53.8% vs 对照组0,P=0.007),其余基线特征亦均衡。中位随访29 个月,与对照组相比,gmDC组的2 年OS率(100.0% vs 40.0%,P=0.001)、2 年PFS率(84.6% vs 20.0%,P=0.001)均显著提高,2 年CIR则显著降低(15.4% vs 80.0%,P=0.001)。多因素分析显示,OS 的风险比(hazard ratio,HR)=0.108(95% CI:0.013 ~ 0.937,P=0.043),PFS 的HR=0.151(95% CI:0.028 ~ 0.811,P=0.027),CIR的亚分布风险比(subdistribution hazard ratio,sHR)=0.108(95% CI:0.025 ~ 0.456,P=0.002)。gmDC组仅出现1 级不良反应,未观察到≥2 级不良事件。结论 在中危AML患者维持治疗中,gmDC疫苗联合CIK展现出改善生存、降低复发风险的潜力,且安全性良好。鉴于本研究的回顾性设计及组间ASCT比例不均衡,该结论有待前瞻性随机对照研究进一步验证。

     

    Abstract: Background Despite achieving minimal residual disease (MRD) negativity through consolidation therapies such as chemotherapy or autologous stem cell transplantation (ASCT), patients with intermediate-risk acute myeloid leukemia (AML) still face a high cumulative incidence of relapse (CIR) of 30% to 50% within two years. Current maintenance therapies struggle to balance efficacy and safety. Objective To investigate the long-term efficacy and safety of genetically modified dendritic cell (gmDC) vaccine combined with cytokine-induced killer (CIK) cells as maintenance therapy in patients with intermediate-risk AML. Methods This retrospective cohort study recruited intermediate-risk AML patients treated at our hospital from January 2013 to December 2023. All enrolled patients achieved MRD negativity after consolidation chemotherapy. Based on treatment, they were classified into the gmDC vaccine combined with CIK maintenance group (gmDC group) and the routine follow-up observation group (control group). The primary endpoint was overall survival (OS). Key secondary endpoints included progression‑free survival(PFS) and CIR. The secondary endpoint was safety. Results A total of 23 patients with intermediate‑risk AML were enrolled in this study, including 13 cases in the gmDC group and 10 cases in the control group. The median ages of the two groups were 34(range, 16 ~ 83) years and 43(range, 19 ~ 62) years, respectively, and the proportions of male patients were 46.2% and 40.0%, respectively, with no statistically significant differences (all P>0.05). Baseline characteristics were balanced between the two groups except for ASCT (gmDC group: 53.8% vs control group: 0, P=0.007). After a median follow-up of 29 months, the gmDC group demonstrated significantly higher 2-year OS (100.0% vs 40.0%, P=0.001) and 2-year PFS (84.6% vs 20.0%, P=0.001), and a significantly lower 2- year CIR (15.4% vs 80.0%, P=0.001) compared with the control group. Multivariable analysis showed that the hazard ratio (HR) for OS was 0.108 (95% CI: 0.013 - 0.937, P=0.043); the HR PFS was 0.151 (95% CI: 0.028 - 0.811, P=0.027); and the subdistribution hazard ratio (sHR) for CIR was 0.108 (95% CI: 0.025 - 0.456, P=0.002). Only grade 1 adverse events occurred in the gmDC group, with no grade ≥ 2 events.Conclusion In maintenance therapy for intermediate-risk AML, the gmDC vaccine combined with CIK shows potential to improve survival and reduce relapse risk, with a favorable safety profile. Given the retrospective design and the imbalance in ASCT rates between the two groups, this conclusion warrants further validation in prospective randomized controlled trials.

     

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