嵌合抗原受体T细胞疗法联合无关脐血移植治疗儿童和青年复发/难治性B细胞急性淋巴细胞白血病：生存率更高但移植后复发率相对较高

Chimeric Antigen Receptor T Cell Therapy followed by Unrelated Cord Blood Transplantation for the Treatment of Relapsed/Refractory B Cell Acute Lymphoblastic Leukemia in Children and Young Adults: Superior Survival but Relatively High Post-Transplantation Relapse.

作者信息

Sun Guangyu, Tang Baolin, Wan Xiang, Yao Wen, Song Kaidi, Tu Meijuan, Geng Liangquan, Qiang Ping, Wu Yue, Zhu Lijun, Wu Yun, Liu Huilan, Zhu Xiaoyu, Sun Zimin

机构信息

Department of Hematology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China; Anhui Provincial Key Laboratory of Blood Research and Applications, Hefei, China; Blood and Cell Therapy Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Department of Hematology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

出版信息

Transplant Cell Ther. 2022 Feb;28(2):71.e1-71.e8. doi: 10.1016/j.jtct.2021.11.011. Epub 2021 Nov 25.

DOI:10.1016/j.jtct.2021.11.011

PMID:34839013

Abstract

Several studies have indicated that chimeric antigen receptor (CAR) T cell therapy followed by allogeneic hematopoietic stem cell transplantation is beneficial for treating patients with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). Whether consolidative unrelated cord blood transplantation (UCBT) is suitable in R/R B-ALL after CAR-T therapy remain uncertain. We aimed to assess the efficacy and safety of CAR-T therapy before UCBT in children and young adults with R/R B-ALL. We retrospectively analyzed 43 patients aged <18 years with R/R B-ALL who underwent single-unit UCBT at the First Affiliated Hospital of the University of Science and Technology of China between February 2012 and November 2020. Among them, 21 patients achieved complete remission (CR) following CAR-T therapy before UCBT (the CAR-T group), and the remaining 22 patients remained in nonremission (NR) without prior CAR-T therapy before UCBT (the NR group). The clinical outcomes in the 2 groups were analyzed. The median time from CAR-T therapy to UCBT was 62 days (range, 42 to 185 days). There were no significant between-group differences in the incidences of grade II-IV acute graft-versus-host disease (GVHD), grade III-IV acute GVHD, and 2-year extensive chronic GVHD. Compared with the NR group, the CAR-T group had a lower 2-year cumulative incidence of transplantation-related mortality and higher probabilities of 2-year overall survival, leukemia-free survival, and GVHD-free relapse-free survival (P = .037, .005, .028, and .017, respectively). However, the 2-year cumulative incidence of relapse (CIR) was comparably high in the 2 groups (26.7% in the CAR-T group and 38.3% in the NR group; P = .41). In the CAR-T group, patients who were minimal residual disease (MRD)-positive before UCBT had a higher CIR compared with those who were MRD-negative before UCBT (66.7% versus 19.2%; P = .006). CAR-T therapy followed by UCBT produces superior survival in R/R B-ALL, but treated patients still have a high post-transplantation relapse rate.

摘要

多项研究表明，嵌合抗原受体（CAR）T细胞疗法后进行异基因造血干细胞移植，对治疗复发或难治性（R/R）B细胞急性淋巴细胞白血病（B-ALL）患者有益。巩固性非亲属脐血移植（UCBT）是否适用于CAR-T治疗后的R/R B-ALL仍不确定。我们旨在评估在接受UCBT前进行CAR-T治疗对R/R B-ALL儿童和年轻成人的疗效和安全性。我们回顾性分析了2012年2月至2020年11月期间在中国科学技术大学附属第一医院接受单单位UCBT的43例年龄<18岁的R/R B-ALL患者。其中，21例患者在UCBT前接受CAR-T治疗后获得完全缓解（CR）（CAR-T组），其余22例患者在UCBT前未接受过CAR-T治疗，仍处于未缓解（NR）状态（NR组）。分析了两组的临床结局。从CAR-T治疗到UCBT的中位时间为62天（范围42至185天）。II-IV级急性移植物抗宿主病（GVHD）、III-IV级急性GVHD和2年广泛性慢性GVHD的发生率在两组之间无显著差异。与NR组相比，CAR-T组2年移植相关死亡率的累积发生率较低，2年总生存率、无白血病生存率和无GVHD无复发生存率的概率较高（P分别为0.037、0.005、0.028和0.017）。然而，两组的2年复发累积发生率（CIR）相当高（CAR-T组为26.7%，NR组为38.3%；P = 0.41）。在CAR-T组中，UCBT前微小残留病（MRD）阳性的患者与UCBT前MRD阴性的患者相比，CIR更高（66.7%对19.2%；P = 0.006）。CAR-T治疗后进行UCBT在R/R B-ALL中产生了更好的生存率，但接受治疗的患者移植后复发率仍然很高。