Full Text:   <1035>

Summary:  <426>

CLC number: 

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2022-10-13

Cited: 0

Clicked: 1215

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Yongxian HU

https://orcid.org/0000-0001-9564-1852

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.10 P.876-880

http://doi.org/10.1631/jzus.B2200128


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


Share this article to: More <<< Previous Article|

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, 2022, 23(10): 876-880.

@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",
volume="23",
number="10",
pages="876-880",
year="2022",
publisher="Zhejiang University Press & Springer",
doi="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
%V 23
%N 10
%P 876-880
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 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
VL - 23
IS - 10
SP - 876
EP - 880
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200128


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:嵌合抗原受T细胞(CAR-T);髓外复发;异基因造血干细胞移植

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]BrudnoJN, SomervilleRPT, ShiV, et al., 2016. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. J Clin Oncol, 34(10):1112-1121.

[2]CruzCRY, MicklethwaiteKP, SavoldoB, et al., 2013. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood, 122(17):2965-2973.

[3]DahlbergA, LeisenringW, BleakleyM, et al., 2019. Prognosis of relapse after hematopoietic cell transplant (HCT) for treatment of leukemia or myelodysplastic syndrome (MDS) in children. Bone Marrow Transplant, 54(8):1337-1345.

[4]DingLW, SunQY, MayakondaA, et al., 2017. Mutational profiling of acute lymphoblastic leukemia with testicular relapse. J Hematol Oncol, 10:65.

[5]FabrizioVA, PhillipsCL, LaneA, et al., 2022. Tisagenlecleucel outcomes in relapsed/refractory extramedullary ALL: a pediatric real world CAR consortium report. Blood Adv, 6(2):600-610.

[6]GauthierJ, BezerraED, HirayamaAV, et al., 2021. Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies. Blood, 137(3):323-335.

[7]HuangH, WuHW, HuYX, 2020. Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(1):29-41.

[8]KochenderferJN, DudleyME, CarpenterRO, et al., 2013. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood, 122(25):4129-4139.

[9]LeeDW, KochenderferJN, Stetler-StevensonM, et al., 2015. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet, 385(9967):517-528.

[10]MaudeSL, FreyN, ShawPA, et al., 2014. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med, 371(16):1507-1517.

[11]MaudeSL, LaetschTW, BuechnerJ, et al., 2018. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med, 378(5):439-448.

[12]NguyenK, DevidasM, ChengSC, et al., 2008. Factors influencing survival after relapse from acute lymphoblastic leukemia: a children’s oncology group study. Leukemia, 22(12):2142-2150.

[13]OriolA, VivesS, Hernández-RivasJM, et al., 2010. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA study group. Haematologica, 95(4):589-596.

[14]ParkJH, RiviereI, GonenM, et al., 2018. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med, 378(5):449-459.

[15]SpyridonidisA, LabopinM, SchmidC, et al., 2012. Outcomes and prognostic factors of adults with acute lymphoblastic leukemia who relapse after allogeneic hematopoietic cell transplantation. An analysis on behalf of the acute leukemia working party of EBMT. Leukemia, 26(6):1211-1217.

[16]SunWL, MalvarJ, SpostoR, et al., 2018. Outcome of children with multiply relapsed B-cell acute lymphoblastic leukemia: a therapeutic advances in childhood leukemia & lymphoma study. Leukemia, 32(11):2316-2325.

[17]TalekarMK, MaudeSL, HucksGE, et al., 2017. Effect of chimeric antigen receptor-modified T (CAR-T) cells on responses in children with non-CNS extramedullary relapse of CD19+ acute lymphoblastic leukemia (ALL). J Clin Oncol, 35(15 Suppl):10507-10507.

[18]TurtleCJ, HanafiLA, BergerC, et al., 2016. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest, 126(6):2123-2138.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE