JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Secondary donor-derived CD19 CAR-T therapy is safe and efficacious in acute lymphoblastic leukemia with extramedullary relapse after first autologous CAR-T therapy

Author(s): Delin KONG, Tingting YANG, Jia GENG, Ruirui JING, Qiqi ZHANG, Guoqing WEI, He HUANG, Yongxian HU
Affiliation(s): Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; more
Corresponding email(s): 1313016@zju.edu.cn
Key Words: Extramedullary relapse; Allogeneic anti-CD19 chimeric antigen receptor T cells; Haploidentical hematopoietic stem cell transplantation; Acute lymphoblastic leukemia

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Delin KONG, Tingting YANG, Jia GENG, Ruirui JING, Qiqi ZHANG, Guoqing WEI, He HUANG, Yongxian HU. Secondary donor-derived CD19 CAR-T therapy is safe and efficacious in acute lymphoblastic leukemia with extramedullary relapse after first autologous CAR-T therapy[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2200128

@article{title="Secondary donor-derived CD19 CAR-T therapy is safe and efficacious in acute lymphoblastic leukemia with extramedullary relapse after first autologous CAR-T therapy",
author="Delin KONG, Tingting YANG, Jia GENG, Ruirui JING, Qiqi ZHANG, Guoqing WEI, He HUANG, Yongxian HU",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2200128"
}

%0 Journal Article
%T Secondary donor-derived CD19 CAR-T therapy is safe and efficacious in acute lymphoblastic leukemia with extramedullary relapse after first autologous CAR-T therapy
%A Delin KONG
%A Tingting YANG
%A Jia GENG
%A Ruirui JING
%A Qiqi ZHANG
%A Guoqing WEI
%A He HUANG
%A Yongxian HU
%J Journal of Zhejiang University SCIENCE B
%P 876-880
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2200128"

TY - JOUR
T1 - Secondary donor-derived CD19 CAR-T therapy is safe and efficacious in acute lymphoblastic leukemia with extramedullary relapse after first autologous CAR-T therapy
A1 - Delin KONG
A1 - Tingting YANG
A1 - Jia GENG
A1 - Ruirui JING
A1 - Qiqi ZHANG
A1 - Guoqing WEI
A1 - He HUANG
A1 - Yongxian HU
J0 - Journal of Zhejiang University Science B
SP - 876
EP - 880
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2200128"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.

自体CAR-T治疗后髓外复发的性淋巴细胞白血病患者再次应用供体来源的CD19 CAR-T治疗是安全有效的

孔德麟^1,2,3,4，杨婷婷^1,2,3,4，耿佳⁵，荆瑞瑞^1,2,3,4，张棋琦^1,2,3,4，魏国庆^1,2,3,4，黄河^1,2,3,4，胡永仙^1,2,3,4
¹浙江大学医学院附属第一医院骨髓移植中心，中国杭州市，310003
²浙江大学医学中心良渚实验室，中国杭州市，311121
³浙江大学血液学研究所，中国杭州市，310058
⁴干细胞与细胞免疫治疗浙江省工程研究中心，中国杭州市，310058
⁵浙江大学医学院附属第一医院放射科，中国杭州市，310003
目的：尽管嵌合抗原受T（CAR-T）细胞桥接异基因造血干细胞移植（allo-HSCT）对于难治/复发B细胞恶性肿瘤已经显示出了显著的治疗效果，但仍有一小部分患者会出现疾病复发。
创新点：供体来源的CAR-T细胞可通过移植物的抗白血病作用发挥抗肿瘤作用，且安全性较好，因此可作为移植后复发B系急性淋巴细胞白血病（B-ALL）治疗的选择之一。
方法：本研究报告了一位62岁的女性患者，她被诊断为CD19阳性B-ALL。在首次自体CAR-T桥接异基因造血干细胞治疗后，患者很快出现髓外复发。随后患者接受了供体来源的CD19 CAR-T治疗。在回输一个月后，患者骨髓常规检查结果表明髓内无白血病细胞，并且MRD阴性。此外，正电子发射计算机断层扫描系统（PET/CT）提示髓外病灶完全消失。
结论：二次异体CAR-T治疗可以快速有效地治疗髓外白血病，且移植物抗宿主病（GVHD）发生风险低，因此可作为移植后疾病复发的治疗选择之一。

关键词组：嵌合抗原受T细胞（CAR-T）；髓外复发；异基因造血干细胞移植

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自体CAR-T治疗后髓外复发的性淋巴细胞白血病患者再次应用供体来源的CD19 CAR-T治疗是安全有效的

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