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探讨嵌合抗原受体 T 细胞治疗后异基因造血细胞移植的困境:移植还是不移植?

Exploring the Dilemma of Allogeneic Hematopoietic Cell Transplantation after Chimeric Antigen Receptor T Cell Therapy: To Transplant or Not?

机构信息

Department of Hematology-BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece.

BReMeL Βiopharmaceutical and Regenerative Medicine Laboratories, Thessaloniki, Greece.

出版信息

Biol Blood Marrow Transplant. 2020 Aug;26(8):e183-e191. doi: 10.1016/j.bbmt.2020.04.003. Epub 2020 Apr 15.


DOI:10.1016/j.bbmt.2020.04.003
PMID:32304874
Abstract

Patients with refractory or relapsed (R/R) B cell acute lymphoblastic leukemia (B-ALL) and highly aggressive B cell non-Hodgkin lymphoma (B-NHL) have a very dismal prognosis and limited treatment options. The advent of chimeric antigen receptor (CAR) T cell therapy constitutes a milestone in current cell and gene therapies, covering the unmet need of treatment of high-risk patients and bringing immunotherapies one step closer toward cancer therapeutics, including hematologic malignancies. CAR T cells targeting CD19 antigen have shown startling remission rates in heavily pretreated B-ALL and B-NHL patients, in whom CAR T cell therapy may sometimes be their last-resort treatment. However, a high proportion of these patients evade immune surveillance by CAR T cells losing their initial deep responses, which leads to disease recurrence as either CD19-positive or CD19-negative relapse. As a result, many investigators have questioned the need for consolidative allogeneic hematopoietic stem cell transplantation (allo-HCT) after CAR T cell therapy, once a patient has achieved remission. There remains much controversy regarding whether CAR T cells should be a bridge therapy to allo-HCT or a definitive treatment, owing to the paucity of strong evidence-based data. In this context, here we review the existing data regarding the necessity, safety, and outcomes of allo-HCT performed after autologous anti-CD19 CAR T cell therapy in B-ALL and B-NHL patients.

摘要

对于难治性或复发性(R/R)B 细胞急性淋巴细胞白血病(B-ALL)和侵袭性高 B 细胞非霍奇金淋巴瘤(B-NHL)患者,其预后极差,治疗选择有限。嵌合抗原受体(CAR)T 细胞疗法的出现是当前细胞和基因治疗的一个里程碑,满足了高危患者的治疗需求,并使免疫疗法在癌症治疗方面更进一步,包括血液系统恶性肿瘤。针对 CD19 抗原的 CAR T 细胞在经过大量预处理的 B-ALL 和 B-NHL 患者中显示出惊人的缓解率,在这些患者中,CAR T 细胞疗法有时可能是他们的最后治疗选择。然而,相当一部分患者通过 CAR T 细胞逃避免疫监视,失去初始的深度反应,从而导致疾病复发,无论是 CD19 阳性还是 CD19 阴性复发。因此,许多研究人员质疑在 CAR T 细胞治疗后是否需要进行巩固性同种异体造血干细胞移植(allo-HCT),一旦患者达到缓解。由于缺乏强有力的循证数据,CAR T 细胞是否应作为 allo-HCT 的桥接治疗或确定性治疗,仍存在很大争议。在这种情况下,我们在此回顾了关于自体抗 CD19 CAR T 细胞治疗后在 B-ALL 和 B-NHL 患者中进行 allo-HCT 的必要性、安全性和结果的现有数据。

相似文献

[1]
Exploring the Dilemma of Allogeneic Hematopoietic Cell Transplantation after Chimeric Antigen Receptor T Cell Therapy: To Transplant or Not?

Biol Blood Marrow Transplant. 2020-8

[2]
[Allogeneic donor-derived CD19 CAR-T therapy of relapsed B-cell acute lmphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2021-5-14

[3]
Efficacy and safety of CD19 CAR-T cell therapy for acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation.

Int J Hematol. 2022-9

[4]
How to Combine the Two Landmark Treatment Methods-Allogeneic Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Together to Cure High-Risk B Cell Acute Lymphoblastic Leukemia?

Front Immunol. 2020

[5]
Hematopoietic Cell Transplantation after CD19 Chimeric Antigen Receptor T Cell-Induced Acute Lymphoblastic Lymphoma Remission Confers a Leukemia-Free Survival Advantage.

Transplant Cell Ther. 2022-1

[6]
[Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia].

Zhonghua Xue Ye Xue Za Zhi. 2024-1-14

[7]
Safety of allogeneic hematopoietic cell transplant in adults after CD19-targeted CAR T-cell therapy.

Blood Adv. 2019-10-22

[8]
[Maintenance therapy following CD19 CAR-T treatment for relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2020-6-14

[9]
Role of chimeric antigen receptor T-cell therapy: bridge to transplantation or stand-alone therapy in pediatric acute lymphoblastic leukemia.

Curr Opin Hematol. 2021-11-1

[10]
Chimeric Antigen Receptor T Cell Therapy for Pediatric B-ALL: Narrowing the Gap Between Early and Long-Term Outcomes.

Front Immunol. 2020

引用本文的文献

[1]
Advances in Gene Therapy with Oncolytic Viruses and CAR-T Cells and Therapy-Related Groups.

Curr Issues Mol Biol. 2025-4-10

[2]
Quartic CAR-T Cell Bridging to Twice Allo-HSCT Therapy in a Patient with Acute Lymphoblastic Leukemia.

Transfus Med Hemother. 2023-8-22

[3]
Use of blinatumomab and CAR T-cell therapy in children with relapsed/refractory leukemia: A case series study.

Front Pediatr. 2023-1-16

[4]
Relapse Mechanism and Treatment Strategy After Chimeric Antigen Receptor T-Cell Therapy in Treating B-Cell Hematological Malignancies.

Technol Cancer Res Treat. 2022

[5]
Immunotherapy and Allogeneic Bone Marrow Transplantation in B Acute Lymphoblastic Leukemia: How to Sequence?

Clin Hematol Int. 2022-5-11

[6]
Point-of-care anti-CD19 CAR T-cells for treatment of relapsed and refractory aggressive B-cell lymphoma.

Transplant Cell Ther. 2022-5

[7]
The Emerging Role of CAR T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma.

J Pers Med. 2022-2-1

[8]
Impact of High Disease Burden on Survival in Pediatric Patients with B-ALL Treated with Tisagenlecleucel.

Transplant Cell Ther. 2022-2

[9]
Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy.

Front Immunol. 2021

[10]
CAR-T after Stem Cell Transplantation in B-Cell Lymphoproliferative Disorders: Are They Really Autologous or Allogenic Cell Therapies?

Cancers (Basel). 2021-9-17

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