CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD72 作为 CD19 CAR-T 治疗后 R/R B-ALL 纵向微小残留病监测的补充性 B 系标志物
英文原题：CD72 as a complementary B-lineage marker for longitudinal measurable residual disease surveillance after CD19 CAR-T therapy in R/R B-ALL.
查看英文原题
CD72 as a complementary B-lineage marker for longitudinal measurable residual disease surveillance after CD19 CAR-T therapy in R/R B-ALL.
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中文摘要
本研究旨在评估CD72作为不依赖CD19的B系设门标志物，用于CD19 CAR-T 治疗后复发/难治性B细胞急性淋巴细胞白血病（R/R B-ALL）纵向可测量残留病（MRD）监测的可行性。在66份B-ALL样本中进行相关性分析，比较使用CD72、CD19和胞质CD79a进行MRD检测的结果。
进一步在129例白血病患者中评估CD72表达特异性。此外，回顾性分析2021年1月至2022年12月期间在注册临床试验（ChiCTR-IIh-16008711；NCT03173417）中接受自体CD19 CAR-T 治疗的129例R/R B-ALL患者，随访持续至2025年1月。CD72设门与基于CD19和cCD79a的策略在MRD评估中显示出极好的一致性。CD72表达在B-ALL中表现出高特异性，阳性率为95.77%，而AML为29.27%，T-ALL为23.53%。所有129例经过重度预处理的患者在CAR-T 输注后第28天均达到MRD阴性CR，随后接受allo-HSCT，中位间隔为54天（范围，40-338）。随访期间共有16例患者发生MRD复发，包括4例临床确诊的CD19阴性复发，这些复发仍保留CD72表达。
CAR-T 前MRD 1%的患者较MRD >1%的患者更早出现B细胞恢复（中位30 [18-45]天 vs. 32 [26-79]天，p = 0.028）。MRD 1%队列与MRD >1%队列相比，3年总生存率显著改善（88.1% vs. 69.2%，p = 0.014）。MRD 1%队列的3年MRD复发累积发生率显著低于MRD >1%队列（3.96% vs. 17.95%，p = 0.019），而 MRD 1% 队列的非复发死亡率在数值上也更低（5.92% vs. 17.95%，p = 0.053）。多因素分析确定 KMT2A 重排、IKZF1 突变、TP53 突变和 CAR-T 前 MRD 升高是较差结局的独立预测因素。CD72 是 CD19 CAR-T 治疗后纵向 MRD 监测的一种可行的补充性 B 系标志物。在临床确认的 CD19 阴性复发中 CD72 表达得以保留，支持其在靶向治疗后 CD19 表达丢失时的潜在应用价值。
展开英文摘要原文
This study aimed to evaluate the feasibility of CD72 as a complementary CD19-independent B-lineage gating marker for longitudinal measurable residual disease (MRD) surveillance in relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) following CD19 CAR-T therapy. Correlation analyses were performed in 66 B-ALL samples to compare MRD detection using CD72, CD19, and cytoplasmic CD79a. CD72 expression specificity was further evaluated in 129 leukemia patients.
In addition, 129 patients with R/R B-ALL treated with autologous CD19 CAR-T therapy in registered clinical trials (ChiCTR-IIh-16008711; NCT03173417) between January 2021 and December 2022 were retrospectively analyzed, with follow-up continued until January 2025. CD72 gating showed excellent concordance with both CD19- and cCD79a-based strategies for MRD assessment. CD72 expression demonstrated high specificity in B-ALL, with a positivity rate of 95. 77%, compared with 29. 27% in AML and 23. 53% in T-ALL. All 129 heavily pretreated patients achieved MRD-negative CR at day 28 after CAR-T infusion and subsequently underwent allo-HSCT, with a median interval of 54 days (range, 40-338). A total of 16 patients experienced MRD relapse during follow-up, including four clinically confirmed CD19-negative relapses that retained CD72 expression. Patients with pre-CAR-T MRD 1% showed earlier B-cell recovery than those with MRD >1% (median 30 [18-45] vs.
32 [26-79] days, p = 0. 028). The MRD 1% cohort demonstrated significantly improved 3-year overall survival compared with the MRD >1% cohort (88. 1% vs. 69. 2%, p = 0. 014). The 3-year cumulative incidence of MRD relapse was significantly lower in the MRD 1% cohort than in the MRD >1% cohort (3. 96% vs. 17. 95%, p = 0. 019), while non-relapse mortality was also numerically lower in the MRD 1% cohort (5. 92% vs. 17. 95%, p = 0. 053).
Multivariate analysis identified KMT2A rearrangement, IKZF1 mutation, TP53 mutation, and elevated pre-CAR-T MRD as independent predictors of inferior outcomes. CD72 represents a feasible complementary B-lineage marker for longitudinal MRD surveillance following CD19 CAR-T therapy. Retention of CD72 expression in clinically confirmed CD19-negative relapses supports its potential utility when CD19 expression is lost after targeted therapy.
论文信息
- 作者
- Chen M、Zhou J、Zhao W、Long J、Fu M、Zhang X、Li Y、Zhang G
- 第一作者单位
- Department of Pathology and Laboratory Medicine, Beijing Lu Daopei Hospital, Beijing, China.China
- 通讯作者单位
- Department of Clinical Laboratory, Hebei Yanda Lu Daopei Hospital, Langfang, China.China
- 期刊
- Cytometry. Part B, Clinical cytometry2026 Aug 3
- 原文标识
- PubMed 42544771 · DOI 10.1002/cyto.b.70057