CD19 CAR-T cell treatment conferred sustained remission in B-ALL patients with minimal residual disease.
CD19 CAR-T cell treatment conferred sustained remission in B-ALL patients with minimal residual disease.
复制标题
CD19 CAR-T 细胞治疗使具有微小残留病的 B-ALL 患者获得持续缓解。
DOI：
10.1007/s00262-021-02941-4
复制
发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Zhao M
中科院分区：
文献类型：
--
作者：
Lu W;Wei Y;Cao Y;Xiao X;Li Q;Lyu H;Jiang Y;Zhang H;Li X;Jiang Y;Meng J;Yuan T;Zhu H;He X;Jin X;Sun R;Sui T;Liu K;Zhao M
化疗后微小残留病（MRD）的持续存在或复发预示着B细胞急性淋巴细胞白血病（B-ALL）的复发。CD 19定向嵌合抗原受体T（CD 19 CAR-T）细胞在B-ALL中显示出有希望的应答。然而，它们在化疗难治性MRD阳性B-ALL中的作用仍不清楚。我们的目的是评估CD 19 CAR-T细胞在MRD阳性B-ALL患者中的有效性和安全性。自2018年1月起，共有14名MRD阳性B-ALL患者接受了一次或多次自体CD 19 CAR-T细胞输注。其中，12例患者在1个周期的CAR-T输注后实现了MRD阴性缓解。中位随访时间为647天（范围172-945天），MRD阳性患者的2年无事件生存率为61.2% ± 14.0%，2年总生存率为78.6 ± 11.0%，显著高于活动性疾病患者（原始细胞≥ 5%或髓外疾病）。此外，MRD患者的细胞因子释放综合征（CRS）级别低于活动性疾病患者。然而，与活动性疾病患者相比，MRD阳性患者的CAR-T细胞扩增峰值无统计学差异。五名患者接受了两次或更多次CAR-T细胞输注，这些患者在随后的输注中显示出CAR-T细胞扩增峰值降低。总之，先发制人的CD 19 CAR-T细胞治疗是一种有效且安全的方法，可使化疗难治性MRD的B-ALL患者获得持续缓解。这些试验在www.chictr.org.cn上注册为ChiCTR-ONN-16009862（2016年11月14日）和ChiCTR 1800015164（2018年3月11日）。在线版本包含补充材料，可通过10.1007/s 00262 -021-02941-4获得。
The persistence or recurrence of minimal residual disease (MRD) after chemotherapy predicts relapse of B-cell acute lymphoblastic leukemia (B-ALL). CD19-directed chimeric antigen receptor T (CD19 CAR-T) cells have shown promising responses in B-ALL. However, their role in chemotherapy-refractory MRD-positive B-ALL remains unclear. Here we aimed to assess the effectiveness and safety of CD19 CAR-T cells in MRD-positive B-ALL patients. From January 2018, a total of 14 MRD-positive B-ALL patients received one or more infusions of autogenous CD19 CAR-T cells. Among them, 12 patients achieved MRD-negative remission after one cycle of CAR-T infusion. At a median follow-up time of 647 days (range 172–945 days), the 2-year event-free survival rate in MRD-positive patients was 61.2% ± 14.0% and the 2-year overall survival was 78.6 ± 11.0%, which were significantly higher than patients with active disease (blasts ≥ 5% or with extramedullary disease). Moreover, patients with MRD had a lower grade of cytokine release syndrome (CRS) than patients with active disease. However, the peak expansion of CAR-T cells in MRD positive patients showed no statistical difference compared to patients with active disease. Five patients received two or more CAR-T cell infusions and these patients showed a decreased peak expansion of CAR-T cell in subsequent infusions. In conclusion, pre-emptive CD19 CAR-T cell treatment is an effective and safe approach and may confer sustained remission in B-ALL patients with chemotherapy-refractory MRD. The trials were registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018). The online version contains supplementary material available at 10.1007/s00262-021-02941-4.
登录
查看更多内容
DOI：
10.1056/nejmoa1609783
发表时间：
2017-03-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kantarjian H;Stein A;Gökbuget N;Fielding AK;Schuh AC;Ribera JM;Wei A;Dombret H;Foà R;Bassan R;Arslan Ö;Sanz MA;Bergeron J;Demirkan F;Lech-Maranda E;Rambaldi A;Thomas X;Horst HA;Brüggemann M;Klapper W;Wood BL;Fleishman A;Nagorsen D;Holland C;Zimmerman Z;Topp MS
通讯作者：
Topp MS
DOI：
10.1038/nrclinonc.2017.148
发表时间：
2018-01
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Neelapu SS;Tummala S;Kebriaei P;Wierda W;Gutierrez C;Locke FL;Komanduri KV;Lin Y;Jain N;Daver N;Westin J;Gulbis AM;Loghin ME;de Groot JF;Adkins S;Davis SE;Rezvani K;Hwu P;Shpall EJ
通讯作者：
Shpall EJ
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
影响因子：
3.5
作者：
Wei, Guoqing;Hu, Yongxian;Huang, He
通讯作者：
Huang, He
影响因子：
11.5
作者：
Jen, Emily Y.;Xu, Qing;Pazdur, Richard
通讯作者：
Pazdur, Richard