CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
TP53 改变对 CD19-CAR-T 细胞治疗后复发/难治性 B 细胞急性淋巴细胞白血病儿童及年轻成人患者结局的影响
英文原题：Impact of TP53 alterations on outcomes in pediatric and young adult patients with relapsed / refractory B-cell acute lymphoblastic leukemia after CD19-CAR T-Cell therapy.
查看英文原题
Impact of TP53 alterations on outcomes in pediatric and young adult patients with relapsed / refractory B-cell acute lymphoblastic leukemia after CD19-CAR T-Cell therapy.
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中文摘要
复发仍然是接受CAR-T 细胞治疗的儿童及年轻成人复发/难治性 B 细胞急性淋巴细胞白血病（r/r B-ALL）患者治疗失败的主要原因。尽管已确定复发预后因素，但仍需进一步完善。
我们开展了一项单中心回顾性研究，纳入 69 例接受 Tisagenlecleucel 治疗的患者，以评估 TP53 改变（TP53 Alt），包括突变和/或缺失，对预后的影响。在 49 例有可用样本的患者中，17 例（34.7%）存在 TP53 Alt。这些患者缓解率显著较低（68.8% vs. 93.8%，p = 0.033），无事件生存期（EFS）和总生存期（OS）更差，且独立于遗传风险分组。TP53 Alt 的中位 EFS 为 3.8 个月（95% CI：1.2-NE），而 TP53 野生型（TP53 wt）为 50.9 个月（95% CI：23.9-NE）。TP53 Alt 的 3 年 EFS 和 OS 分别为 33.1%（95% CI：16.4%-66.6%）和 37.2%（95% CI：19.4%-71.4%），而 TP53 wt 分别为 56.2% 和 81.2%（p = 0.0069 和 p = 0.0010）。这些发现表明，TP53 改变是接受 CAR-T 治疗的 r/r B-ALL 患者的一个强烈不良预后因素。筛查 TP53 Alt 可能指导风险适应策略，包括早期巩固性造血干细胞移植或替代疗法。
展开英文摘要原文
Relapse remains the leading cause of treatment failure in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy. While prognostic factors for relapse have been identified, further refinement is needed.
We conducted a single-center retrospective study of 69 patients treated with Tisagenlecleucel, to evaluate the prognostic impact of TP53 alterations (TP53 Alt ), including mutations and/or deletions. Among 49 patients with available samples, 17 (34. 7%) had TP53 Alt . These patients showed significantly lower remission rates (68. 8% vs. 93. 8%, p = 0.
033) and worse event-free survival (EFS) and overall survival (OS), independent of genetic risk group. Median EFS was 3. 8 months (95% CI: 1. 2-NE) for TP53 Alt versus 50. 9 months (95% CI: 23. 9-NE) for TP53 wild-type (TP53 wt ). Three-year EFS and OS were 33. 1% (95% CI: 16. 4%-66. 6%) and 37. 2% (95% CI: 19. 4%-71. 4%) for TP53 Alt , compared to 56. 2% and 81. 2% for TP53 wt (p = 0. 0069 and p = 0. 0010, respectively).
These findings identify TP53 alterations as a strong adverse prognostic factor in patients with r/r B-ALL treated with CAR-T therapy. Screening for TP53 Alt may guide risk-adapted strategies, including early consolidation with hematopoietic stem cell transplantation or alternative therapies.
论文信息
- 作者
- Alonso-Saladrigues A、Esperanza-Cebollada E、Vicente-Garcés C、Perez-Jaume S、Sánchez-Sierra N、Richarte-Franqués M、Català A、Crespo-Carrasco A
- 第一作者单位
- CAR T-cell Unit. Leukemia and Lymphoma Department. Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Déu de Barcelona, Barcelona, Spain.Spain
- 通讯作者单位
- CAR T-cell Unit. Leukemia and Lymphoma Department. Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Déu de Barcelona, Barcelona, Spain. susana.rives@sjd.es.Spain
- 期刊
- Bone marrow transplantation2026 Jun
- 原文标识
- PubMed 41935222 · DOI 10.1038/s41409-026-02838-9