Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia
Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia
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DOI：
10.1182/blood-2017-04-780155
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发表时间：
2017-10-12
期刊：
影响因子：
20.3
通讯作者：
Berneman, Zwi N.
中科院分区：
文献类型：
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作者：
Anguille, Sebastien;Van de Velde, Ann L.;Berneman, Zwi N.
复发是急性髓系白血病 (AML) 的一个主要问题，会对生存产生不利影响。在这项 2 期研究中，我们研究了用 Wilms 肿瘤 1 (WT1) 信使 RNA (mRNA) 电穿孔的树突状细胞 (DC) 疫苗接种作为缓解后治疗对 30 名复发风险极高的 AML 患者的效果。 13 名患者出现了明显的抗白血病反应。 WT1 转录水平正常化证明，9 名患者实现了分子缓解，其中 5 名患者在中位随访 109.4 个月后持续缓解。其他 4 名患者的病情也得到了稳定。有反应者的五年总生存率 (OS) 高于无反应者（53.8% vs 25.0%；P = 5.01）。在首次完全缓解 (CR1) 时接受 DC 的患者中，疫苗诱导的复发率降低了 25%，且应答者的 5 年无复发生存率高于无应答者（50% vs 7.7%；P < .0001）。在 CR1 期接受 DC 的 65 岁患者中，5 年 OS 分别为 69.2% 和 30.8%，而瑞典急性白血病登记处的这一数字为 51.7% 和 18%。长期临床反应与多表位WT1特异性CD8(+)T细胞循环频率增加相关。长期 OS 与迟发型超敏反应浸润 CD8 1 T 淋巴细胞中的干扰素-g 1 和肿瘤坏死因子-α(+) WT1 特异性反应相关。总之，用 WT1 mRNA 电穿孔 DC 接种 AML 患者可以成为预防或延缓标准化疗后复发的有效策略，从而提高 OS 率，这与诱导 WT1 特异性 CD8(+) T 细胞反应相关。
Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P = 5.01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age 65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD8(+)T cells. Long-term OS was correlated with interferon-g 1 and tumor necrosis factor-alpha(+) WT1-specific responses in delayed-type hypersensitivity-infiltrating CD8 1 T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improvedOSrates, which are correlated with the induction of WT1-specific CD8(+) T-cell response.